Search

Background: Bria-IMT (SV-BR-1-GM) is an off-the-shelf whole tumor cell therapeutic vaccine engineered to express class I & class II HLAs, secrete GM-CSF, and function as antigen-presenting cells; with subsequent enhancements improving in-vitro characteristics. By expressing cancer antigens such as HER2/Neu and PRAME, SV-BR-1-GM also serves as the reservoir of cancer antigens to activates patient’s anti-tumor immune responses. The safety and efficacy of the ongoing clinical trial of SV-BR-1-GM in combination with a PD1 inhibitor are reported. We also report post-hoc exploratory data for patients with advanced metastatic breast cancer (aMBC) treated with SV-BR-1-GM regimens. Methods: Ongoing prospective, phase 1-2, with an expansion randomized phase 2 cohort (NCT03328026; 2018-present) using SV-BR-1-GM with a PD1 inhibitor (pembrolizumab or retifanlimab) with cycles every 3 weeks (16 patients dosed to date). SV-BR-1-GM “monotherapy” (NCT03066947; 2013-8), a completed prospective phase 1-2 results are also presented. Results: A total of 51 patients received any SV-BR-1-GM regimen; 27 in monotherapy (SV) and 24 in combination with a PD-1 inhibitor (CO) currently ongoing: 4 subjects from SV continued on with CO. Median prior regimens = 5; 61% ER or PR+; 6% ER or PR-/HER2+ and 29% triple negative. SV-BR-1-GM was well tolerated. Disease control rate was 40% with SV and 41% with CO in subjects with available assessment(s). Median PFS was 2.7 months with 6 having PFS >150 days (150-226) for SV and 2.6 months with 5 > 150 days (188-308) for CO. Per protocol, 23 patients had anergy testing prior to treatment. Among those with a normal immunologic response (n=13, 56%), disease outcomes included 4 SD and 2 PR (46% CBR) vs anergic patients (n=7, 30%) with 1 SD (14% CBR); 3 patients (13%) with unknown anergy testing had 0% CBR. All 7 anergic patients developed delayed-type hypersensitivity (DTH) injection site responses to SV-BR-1-GM. Subjects with DTH (injection site induration/erythema) had a significant reduction in the risk of progression or death (HR=0.096, 95%CI:0.02-0.50, p6mo). TEAEs occurred in 20/24 (83%) of subjects in CO including 9/24 (38%) with injection site AEs. There were no AEs of special interest eg cytokine storm. There were no Grade 5 and only 6 grade 4 AEs in CO. Conclusions: In an ongoing randomized phase 2, anergic patients had worse outcomes. SV-BR-1-GM was able to illicit an immune response regardless. Responses, stable disease and CBR were seen and associated with immune responses including injection site erythema/induration (DTH), CTC changes and tumor grade I/II. Patients with disease control had better quality of life. SV-BR-1-GM may be able to alter an anergic immune system for clinical benefit. Future pivotal trials will be based upon the ongoing confirmatory randomized clinical trial. Citation Format: Saranya Chumsri, Minal Barve, Chaitali Nangia, Bonnie L. Guerin, Jarrod Holmes, Karim Mohammed, John Knecht, Shaker Dakhil, William V. Williams, Charles Wiseman, Mingjin Chang, Miguel Lopez-Lago, John G. Knecht, Kendrith Rowland, Ralph V. Boccia, Giuseppe Del Priore, Carmen Calfa. Whole cell antigen presenting immune stimulating cells (Bria-IMT) for the treatment of metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT143.

TPS275 Background: Colorectal cancer is the third most prevalent cancer, and the prognosis of patients with advanced metastatic (mCRC) is poor. The efficacy of standard of care (SOC) second-line chemotherapy combinations with anti-vascular endothelial growth factor (VEGF) therapies remains modest. Previously treated advanced mCRC that is microsatellite stable (MSS/pMMR) represents nearly 95% of the metastatic population and remains a high unmet medical need. DKN-01 is a humanized IgG4 monoclonal antibody (mAb) targeted against Dickkopf-related protein 1 (DKK1), a regulator of the Wnt signaling pathway. DKK1 has been identified as a potential oncogenic driver in CRC and has been correlated with 5FU resistance. Therefore, DKK1 expression is a potential predictive biomarker for chemotherapeutic resistance in CRC. Methods: This is a phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate safety and efficacy of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus SOC [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced mCRC patients. In Parts A and B, approximately 150 advanced MSS, BRAF Wild Type mCRC patients with radiographic progression during or following 1 prior line of systemic treatment will be enrolled in the study. Part A is a safety run-in with DKN-01 plus FOLFIRI/FOLFOX and bevacizumab in at least 20 safety evaluable patients. In Part B, approximately 130 patients will be randomized 1:1 to either the experimental (DKN-01 plus FOLFIRI/FOLFOX and bevacizumab) or control arm (FOLFIRI/FOLFOX and bevacizumab), using a central stratified block randomization scheme and stratified based on DKK1 RNAscope tumor percentage score (TPS) (≥1% vs

Fostamatinib demonstrated efficacy in phase 3 trials of adults with immune thrombocytopenia (ITP). Post hoc analysis compared patients who received fostamatinib as second‐line therapy (after steroids ± immunoglobulins) versus third‐or‐later‐line therapy (after ≥2 prior lines of therapy including a second‐line agent). Platelet responses ≥50 000/µl were observed in 25/32 (78%) second‐line and 54/113 (48%) third‐or‐later‐line patients. Bleeding events were less frequent in second‐line (28%) versus third‐or‐later‐line (45%) patients. Responses once achieved tended to be durable in both groups. The safety profile was similar in both groups. In this post hoc analysis, fostamatinib was more effective as second‐line than third‐or‐later‐line therapy for ITP.

Chris LaVallee,1 Isha Bansal,2 Shilpa Kamdar,2 Winghan Jacqueline Kwong,3 Ralph V Boccia4 1Health Outcomes Research, Decision Resources Group, Burlington, MA, USA; 2Analytics, Decision Resources Group, Burlington, MA, USA; 3Health Economics & Outcomes Research, Daiichi Sankyo Inc., Basking Ridge, NJ, USA; 4Center for Cancer and Blood Disorders, P.C, Bethesda, MD, USACorrespondence: Winghan Jacqueline Kwong, Daiichi Sankyo, Inc., 211 Mt Airy Road, Basking Ridge, NJ, 07920, USA, Tel +1 908 992 7063, Email jkwong@dsi.comPurpose: Replacement iron is the main treatment for iron deficiency, but the relationship between initial intravenous (IV) dose and need for additional treatment is unclear. This study explored patterns of IV iron dosing in US clinical practice.Methods: Patient records were obtained for adults who received IV iron for anemia between 2015 and 2017. Patients were classified into four groups: those who received < 1500 mg and ≥ 1500 mg IV iron and those received ≤ 1000 mg and > 1000 mg within 3 weeks of their first dose. The proportion of patients requiring additional IV iron after 30 days of the initial dose was evaluated.Results: Data were obtained for 2959 patients receiving iron sucrose (44.2%), ferric carboxymaltose injection (FCM) (25.8%), and ferumoxytol (FM) (14.3%). Overall, 567 patients (19%) received ≥ 1500 mg of IV iron and 942 (32%) received > 1000 mg of IV iron within the first 21 days. Mean (SD) baseline iron deficit was 1001 mg (312). Patients who received ≥ 1500 mg had a 32% lower probability of receiving additional IV iron than those who received < 1500 mg (adjusted hazard ratio [HR]: 0.68 [95% confidence interval (CI); 0.58, 0.81]) and incurred significantly fewer outpatient visits for all causes (p < 0.001) and IV iron treatment (p < 0.001). Patients who received an initial dose of > 1000 mg had a 41% lower probability of receiving additional IV iron than those who received ≤ 1000 mg (adjusted HR: 0.59 [95% CI; 0.52, 0.67]) and had significantly fewer outpatient visits for all causes (p < 0.001) and IV iron treatment (p < 0.001). Patients receiving FCM required fewer outpatient visits than those receiving FM and other treatments, including a subgroup of patients who initially received > 1000 mg IV iron.Conclusion: Higher doses of IV iron within 3 weeks of first dose may reduce further IV iron treatment needs and outpatient visits.Keywords: anemia, ferric carboxymaltose injection, ferumoxytol, iron sucrose

Erythropoiesis-stimulating agents (ESA) are effective for chemotherapy-induced anemia (CIA) but associated with serious adverse events. Safer alternatives would be beneficial in this population. The efficacy and safety of ferric carboxymaltose (FCM) as monotherapy for CIA was evaluated. This Phase 3, 18-week, double-blind, placebo-controlled study randomized adults with ≥ 4 weeks of chemotherapy remaining for treatment of nonmyeloid malignancies with CIA to FCM (two 15 mg/kg infusions 7 days apart; maximum dose, 750 mg single/1500 mg total) or placebo. The primary efficacy endpoint was percentage of patients with decreases in hemoglobin (Hb) ≥ 0.5 g/dL from weeks 3 to 18; the key secondary efficacy endpoint was change in Hb from baseline to week 18. Inclusion criteria included: (Hb) 8-11 g/dL, ferritin 100-800 ng/mL, and transferrin saturation (TSAT) ≤35%. In 244 patients (n = 122, both groups), the percent of patients who maintained Hb within 0.5 g/dL of baseline from weeks 3 to 18 was significantly higher with FCM versus placebo (50.8% vs. 35.3%; p = 0.01). Mean change in Hb from baseline to week 18 was similar between FCM and placebo (1.04 vs. 0.87 g/dL) but significantly greater with FCM with baseline Hb ≤ 9.9 g/dL (1.08 vs. 0.42 g/dL; p = 0.01). The percent with ≥ 1 g/dL increase from baseline was significantly higher with FCM versus placebo (71% vs. 54%; p = 0.01), occurring in a median 43 versus 85 days (p = 0.001). Common adverse events in the FCM arm included neutropenia (17%), hypophosphatemia (16%), and fatigue (15%). FCM monotherapy effectively maintained Hb and was well tolerated in CIA.

We compared patient-reported outcomes (PROs) with once-weekly carfilzomib 70 mg/m2 (Kd70 mg/m2) vs. twice-weekly carfilzomib 27 mg/m2 (Kd27 mg/m2) plus dexamethasone in relapsed or refractory multiple myeloma (RRMM). Patient-reported convenience/satisfaction collected at Cycle 2, Day 1 was compared between groups using logistic regression. European Organization for Research and Treatment of Cancer QOL Questionnaire (QLQ-C30), MM-module (QLQ-MY20), and EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) questionnaires were administered at baseline, then every other cycle. PROs were compared between groups using mixed models for repeated measures. Times from randomization to first deterioration (TTD) in scores were analyzed using Cox regression. PRO analyses included 469 patients. Once-weekly Kd70 mg/m2 patients reported greater convenience (odds ratio [OR], 4.98; p

In ENDEAVOR, carfilzomib (56 mg/m2) and dexamethasone (Kd56) demonstrated longer progression-free survival (PFS) over bortezomib and dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma (RRMM). Here we evaluated Kd56 vs Vd by baseline renal function in a post hoc exploratory subgroup analysis. The intent-to-treat population included 929 patients (creatinine clearance [CrCL] ≥15 to

Background The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence/duration while maintaining quality of life (QoL) and improving outcomes. Patients and Methods US community sites are enrolling non-transplant-eligible newly diagnosed multiple myeloma (MM) patients with no evidence of progressive disease after 3 cycles of bortezomib-based therapy to receive ixazomib-Rd (up to 39 cycles or until progression/toxicity). Patients use mobile/wearable digital devices to collect actigraphy (activity/sleep) data and electronically complete QoL/treatment satisfaction/medication adherence questionnaires. Primary endpoint: progression-free survival (PFS); key secondary endpoints include response rates and therapy duration. Results At data cutoff, 84 patients had been treated (median age 73 years; 44% ≥ 75 years; 49% male; 15% black/African American; 10% Hispanic/Latino); 62% of patients remain on therapy. Mean duration of total PI therapy was 10.1 months and of ixazomib-Rd was 7.3 months. With 8 months median follow-up, 12-month PFS rate was 86% (95% confidence interval, 73–93) from both the start of bortezomib-based treatment and the start of ixazomib-Rd. Overall response rate was 62% (complete response [CR], 4%; very good partial response [VGPR], 25%; partial response [PR], 33%) after bortezomib-based induction and 70% (CR, 26%; VGPR, 29%; PR, 15%) after iCT. The ixazomib-Rd safety profile was consistent with previous clinical trial data. QoL/treatment satisfaction were maintained. Conclusion US MM-6 patients are representative of the real-world US MM population; iCT may permit prolonged PI-based therapy with promising efficacy, without impacting patients’ QoL/treatment satisfaction., Graphical abstract, While long-term proteasome inhibitor therapy improves outcomes in multiple myeloma, many patients cannot tolerate long-term treatment or may require/prefer to continue treatment outside the hospital/clinic. US MM-6 evaluates in-class transition from parenteral bortezomib- to oral ixazomib-based therapy in routine clinical practice. Preliminary results indicate feasibility, prolonged duration of therapy, and promising efficacy and treatment adherence/satisfaction.

Data from REVEAL (Prospective Observational Study of Patients With Polycythemia Vera in US Clinical Practices; n = 2309), the first study of its kind, confirm that many patients experience quality of life and work productivity impairments that might negatively affect their lives. In the future, longitudinal data from REVEAL will be important for evaluating how such burdens change over time. Background: Patients with polycythemia vera (PV) often experience symptoms that adversely affect their quality of life (QoL). The ongoing, prospective, observational REVEAL (Prospective Observational Study of Patients With Polycythemia Vera in US Clinical Practices) study was designed to collect contemporary data regarding burden of disease, clinical management, patient-reported outcomes (PROs), and health care resource utilization from adult patients with PV in the United States. Patients and Methods: Data on PROs were collected at enrollment using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; range, 0–100); the European Organization for Research and Treatment of Cancer—Core Quality of Life Questionnaire, version 3.0 (EORTC QLQ-C30; range, 0–100); and the Work Productivity and Activity Impairment Questionnaire—Specific Health Problem (WPAI-SHP; range, 0%−100%). Results: Among 2309 patients, mean (SD) disease duration was 5.8 (6.1) years and Chanson Comorbidity Index was 3.4 (0.8); 54.0% (1247/2309) were male. Mean (SD) MPN-SAF TSS was 18.8 (15.5). The most common symptoms were fatigue (80.1% [1844/2302]), early satiety (60.9% [1402/2302]), and inactivity (57.6% [1324/2302]). The most common severe symptoms were fatigue (16.8% [387/2302]), itching (13.4% [308/2302]), and inactivity (1 1.8% [271/2302]). The mean (SD) EORTC QLQ-C30 global health status/QoL score was 73.1 (23.2): mean functional subscale scores ranged from 80.5 (23.9) for cognitive functioning to 85.7 (24.6) for social functioning. The mean WPAI-SHP activity impairment score was 19.7% (n = 2300). Employed patients had mean WPAI-SHP scores for absenteeism, presenteeism, and overall work impairment of 3.2% (n = 810), 12.1% (n = 807), and 13.4% (n = 802), respectively. Conclusion: These data confirm that many patients with PV experience symptoms, QoL impairments, and work productivity impairments that negatively affect their lives. Longitudinal data from REVEAL will be important for evaluating how PROs change over time in these patients.

Background: SUMOylation, a post-translational modification analogous to ubiquitination, attaches a small, ubiquitin-like modifier (SUMO) to target proteins. SUMOylation plays a central role in the immune system by regulating type I interferon (IFN-I) expression, thereby functioning to constrain the innate immune response (Decque Nat Immunol 2016), and limit tumor immune surveillance. The SUMOylation pathway is often overexpressed in multiple myeloma (MM) and is associated with poor outcomes (Driscoll Blood 2010). TAK-981 is a first-in-class, small-molecule inhibitor of SUMO-activating enzyme, which blocks the SUMOylation cascade (Langston J Med Chem 2021) and increases IFN-I production and signaling in innate immune cells (Nakamura AACR 2019). In ex vivo assays, TAK-981 activated the IFN-I pathway, increased phagocytic activity of monocyte-derived macrophages, and increased natural killer (NK) cell cytotoxicity via IFN-I signaling (Nakamura AACR 2019). The ability of TAK-981 to promote activation of macrophages and NK cells provides a mechanistic rationale for its use in combination with monoclonal antibodies (mAbs) reliant on antibody-dependent cellular cytotoxicity and phagocytosis; in vivo experiments have demonstrated synergistic activity between TAK-981 and rituximab, and between TAK-981 and the anti-CD38 mAbs daratumumab (dara) (Nakamura SITC 2020) or mezagitamab (meza; TAK-079; Figure 1). Patients with MM who have disease refractory to the three most effective classes of anti-myeloma therapies (proteasome inhibitors [PIs], immunomodulatory drugs [IMiDs], and anti-CD38 mAbs) have a poor prognosis, with median survival 9.2 months (Gandhi Leukemia 2019). Given the incurable nature of advanced MM and the highly complex mechanisms of resistance, continued efforts to better understand MM biology at the time of relapse and to translate this into effective treatment combinations are needed. Combination therapies that engage the immune system to treat MM may offer substantial clinical benefit. Methods: To be eligible for this multicenter, open-label, Phase 1b/2 trial (NCT04776018), patients must have failed at least 3 prior lines of anti-myeloma therapy, have MM disease that is triple-class refractory (defined as refractory/intolerant to ≥1 PI and ≥1 IMiD, and refractory to ≥1 anti-CD38 mAb), and have demonstrated disease progression on their last therapy. Prior CAR-T therapy is allowed. Patients will be assigned to TAK-981 plus subcutaneous (SC) meza (Phase 1 Part 1) or SC dara (dara and hyaluronidase-fihj; Phase 1 Part 2). The primary objectives of Phase 1b are to determine safety and tolerability, and to select the recommended Phase 2 dose (RP2D) and schedule for TAK-981 with each mAb; secondary objectives are to evaluate preliminary antitumor activity, to characterize TAK-981 pharmacokinetics (PK), and to explore pharmacodynamic (PD) markers of TAK-981 target engagement and SUMOylation pathway inhibition. Approximately 30 patients will participate in the Phase 1b Part 1 dose escalation of TAK-981 plus meza (~15 patients per dosing schedule), and ~15 patients will participate in the Phase 1b Part 2 dose escalation of TAK-981 plus SC dara. The primary objective of Phase 2 is to evaluate the efficacy of TAK-981 at the RP2D in combination with an anti-CD38 mAb; ~36 patients will be enrolled. In Phase 1b, patients will receive TAK-981 via a 1-hour intravenous infusion either on days 1, 4, 8, 11, and 15 (twice weekly; BIW) or on days, 1, 8, 15, and 22 (weekly; QW) for 2x 28-day cycles, then 8x every other week, then monthly. Meza 600 mg SC or dara 1800 mg SC will be given 8x weekly, 8x every other week, then monthly, in a 28-day cycle (Figure 2). Treatment will continue until disease progression or unacceptable toxicity (max. 24 cycles). TAK-981 dose escalation will proceed from 60 mg BIW, a dose shown to be pharmacologically active in a first-in-human, single-agent TAK-981 study (TAK-981-1002; data on file). Dose escalation will be guided by Bayesian Optimal Internal Design with Informative Prior (iBOIN) plus consideration of other safety, clinical, PK, and PD data. The iBOIN design selects the true maximum tolerated dose (if any) with high accuracy by allocating more patients to dose levels with a prior dose-limiting toxicity probability closest to the target of 0.3. This study is currently enrolling patients, with the first patient dosed in May 2021. Figure 1 Figure 1. Disclosures Lonial: AMGEN: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Research Funding; Merck: Honoraria; Abbvie: Consultancy, Honoraria. Boccia: BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; Morphosis: Honoraria, Speakers Bureau. Yimer: Beigene: Speakers Bureau; Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau; Janssen: Speakers Bureau; GSK: Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Pharmacyclics: Speakers Bureau; Texas Oncology: Current Employment. Levy: Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Morphosys: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Dova: Consultancy, Other: Promotional speaker; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Amgen Inc.: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; GSK: Consultancy, Other: Promotional speaker; Epizyme: Consultancy, Other: Promotional speaker; Novartis: Consultancy, Other: Promotional speaker; AbbVie: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Beigene: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau. Abonour: Takeda: Research Funding; GSK: Consultancy, Honoraria, Research Funding; Celgene-BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jensen: Honoraria, Research Funding. Mohan: Medical College of Wisconsin: Current Employment. Girnius: BMS: Honoraria, Speakers Bureau; Celgene: Speakers Bureau; Genentech: Honoraria; GSK: Honoraria, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Speakers Bureau. Rosenbaum: Takeda: Honoraria; Akcea: Honoraria; Janssen: Honoraria. Nadeem: Karyopharm: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees. Berg: Takeda: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Chao: Takeda: Current Employment. Berger: Takeda Development Center Americas, Inc.: Current Employment. Nakamura: Takeda Development Center Americas, Inc.: Current Employment. Zhang: Takeda: Current Employment. Song: Takeda Pharmaceuticals International Co.: Current Employment. Ward: Takeda: Current Employment. Proscurshim: Takeda Pharmaceuticals: Current Employment, Current holder of individual stocks in a privately-held company. Kumar: Novartis: Research Funding; Tenebio: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Beigene: Consultancy; Bluebird Bio: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Oncopeptides: Consultancy; Amgen: Consultancy, Research Funding; Carsgen: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. OffLabel Disclosure: Study of the investigational agent TAK-981 in combination with daratumumab and hyaluronidase-fihj or the investigational agent mezagitamab (TAK-079).

Introduction Ruxolitinib (RUX) is an FDA-approved oral, selective inhibitor of Janus kinase (JAK) 1/2 for the treatment of patients with intermediate or high-risk myelofibrosis and polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. Preclinical studies from our laboratory have demonstrated that RUX in combination with dexamethasone shows marked anti-myeloma effects both in vitro and in vivo. Specifically, RUX blocks expression of Mucin 1 whose function is linked to lenalidomide (LEN) resistance, downregulates PD-L1 and PD-L2 expression and reduces tumor stimulatory M2 macrophage polarization in multiple myeloma (MM) bone marrow. Recently published results from a Phase 1 trial for 28 heavily previously treated MM patients administered RUX, LEN and methylprednisolone (MP) demonstrated that the therapy was well tolerated and RUX overcame refractoriness to LEN and steroids (Berenson et al., Clin Cancer Res. 2020). The clinical benefit rate (CBR) and overall response rate (ORR) were 46% and 28%, respectively, and all 12 responding patients were refractory to LEN. We evaluated whether the combination of RUX and steroids without LEN was active for treating similar patients through treatment of a cohort within the current trial using this two-drug combination (NCT03110822). Methods MM patients must have failed > 3 prior regimens and have been exposed to a proteasome inhibitor and LEN. Patients were treated orally (PO) with 15 mg RUX twice daily on days 1-28 of a 28-day cycle and 40 mg MP every other day. The treatment of this two-drug combination was continued until disease progression (PD). Once PD was confirmed, LEN at 10 mg PO daily on days 1-21 of a 28-day cycle was added to the regimen. Primary endpoints were safety, ORR and CBR. Results As of July 15, 2021, 27 patients were enrolled. The median age was 64 years (range, 46-85), and 17 (63%) were male. Patients received a median of 4 (range, 3-11) prior treatments including LEN and steroid-containing regimens to which they were all refractory. Twenty-six patients have completed at least 1 full cycle of therapy; and, thus, were evaluable for efficacy. The ORR and CBR were 35% (n=9) and 39% (n=10), respectively. Notably, all 10 responding patients were refractory to LEN (i.e., progressed while on or within 8 weeks of last dosage). The remaining patients showed stable disease (n=12) or PD (n=4). The median follow-up was 13 months. The median progression-free survival was 4 months (range, 1-21). The median duration of response was 11 months (range, 1-20). Of 13 patients who progressed on the two-drug combination and had LEN added to their regimen, 6 patients responded (3 MR and 3 PR). Nine patients experienced SAEs including sepsis (12%), sepsis with neutropenic fever (4%), thrombocytopenia (4%), hyperglycemia (4%), neutropenia (4%), anemia (4%), acute heart failure (4%), rotator cuff tear (4%), osteomyelitis (4%), aspiration pneumonia (4%), pneumonia and pneumothorax (4%), and deep venous thrombosis (4%). Two patients died (one each from pneumonia and PD). Conclusions This ongoing Phase 1 trial is the first study demonstrating clinical activity of the two-drug combination of the JAK inhibitor RUX with steroids for MM patients. The treatment was well tolerated and shows promising efficacy for treating heavily previously treated MM patients. Because of this, additional studies are being conducted with higher doses of RUX in combination with MP for this patient population. Disclosures Vescio: Janssen: Speakers Bureau; Karyopharm: Speakers Bureau; GlaxoSnithKlein: Speakers Bureau; Amgen: Speakers Bureau. OffLabel Disclosure: Ruxolitinib is being investigated off-label to determine if it shows anti-myeloma activity in combination with steroids for relapsed/refractory myeloma patients.

This Phase II trial evaluated the efficacy of bendamustine, bortezomib and rituximab in patients with previously untreated low-grade lymphoma. Eligible patients had low grade lymphoma with no previous systemic disease treatment. Treatment for all patients was given in 28-day cycles for a maximum of 6 cycles. Patients received rituximab 375 mg/m2 intravenously (IV) on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6; bendamustine 90 mg/m2 IV on days 1 and 2; and bortezomib 1·6 mg/m2 IV on days 1, 8 and 15. Patients were permitted to begin maintenance treatment with rituximab 6 months after completion of study treatment and after 6-month follow-up assessments had been conducted. Fifty-four eligible patients were enrolled. The most common grade 3/4 toxicities were leucopenia (28%), neutropenia (30%) and lymphopenia (17%). There were no treatment-related deaths and 1 unrelated death on study (embolic stroke). The overall response rate was 94% for all patients. The median follow-up was 54 months. Kaplan-Meier estimates of progression-free survival and overall survival at 36 months were 75% and 88%, respectively. The treatment regimen was well tolerated and produced high response rates. Further study of this regimen in patients with previously untreated lymphoma is warranted.

2552 Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel engineered cytokine that selectively binds the intermediate-affinity interleukin-2 receptor to preferentially activate CD8+ T and natural killer (NK) cells with minimal expansion of regulatory T cells (Tregs),designed for use as a cancer immunotherapy. ARTISTRY-2 (NCT03861793) is an ongoing phase 1/2 study evaluating the safety, efficacy, and pharmacokinetic and pharmacodynamic (PD) responses of subcutaneous (SC) nemvaleukin in combination with pembrolizumab in patients (pts) with advanced solid tumors. Methods: In phase 1, cohort-specific doses of SC nemvaleukin are administered on an every-7-day (q7d) or every-21-day (q21d) schedule during a 6-week monotherapy lead-in period, followed by combination with pembrolizumab 200 mg q21d. We present safety, PD effects, and preliminary clinical activity outcomes as of 12/02/2020. Results: 57 pts received nemvaleukin doses ranging from 0.3 mg to 6 mg q7d or 1 mg to 10 mg q21d. The most frequent tumor types (> 5 pts) were colorectal, pancreatic, ovarian, and lung; median number of prior therapies was 4. Treatment-related adverse events (TRAEs) in > 30% pts overall were pyrexia (43.9%), chills (38.6%), injection site erythema (33.3%), injection site reaction (33.3%), and fatigue (31.6%). 3 mg q7d (n = 7) had no drug-related dose reductions, discontinuations, or deaths during the monotherapy or combination periods. 6 mg was declared the maximum tolerated dose (MTD) for q7d dosing as 2 of 8 pts experienced dose-limiting toxicities (DLTs). For 6 mg q21d (n = 7), no drug-related dose reductions, discontinuations, or deaths have occurred during the monotherapy period; combination period data are not mature. 10 mg was declared the MTD for q21d dosing as 1 of 9 pts experienced DLTs and 3 had TRAEs leading to dose reductions. Systemic exposure to nemvaleukin increased with increasing dose. Increases in NK cells and CD8+ T cells of approximately 16-fold and 3-fold, respectively, at 3 mg q7d, and approximately 8-fold and 3-fold, respectively, at 6 mg q21d were observed, with minimal change in Tregs. 46 pts had at least 1 on-treatment scan as of the data cutoff date, and 30 (65%) had stable disease (SD) on the first scan. Of the 30 pts with ≥2 scans, 13 (43%) had 2+ consecutive scans of SD. 16 of 57 pts remain on therapy. Antitumor activity data for more recent cohorts are still maturing. Based on the totality of the safety, PD effects, and antitumor activity data, 3 mg q7d was selected as the RP2D for SC nemvaleukin. Conclusions: SC nemvaleukin 3 mg q7d was generally well tolerated as monotherapy and in combination with pembrolizumab, and demonstrated robust PD effects on NK cells and CD8+ T cells with minimal expansion of Tregs. These PD effects are similar to or greater than those observed with intravenous nemvaleukin. Thus, 3 mg q7d was selected as RP2D; phase 2 expansion cohorts for combination with pembrolizumab are enrolling. Clinical trial information: NCT03861793.

Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). Results A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Conclusion Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

Purpose Chemotherapy-induced febrile neutropenia (FN) causes treatment delays and interruptions and can have fatal consequences. Current guidelines provide recommendations on granulocyte colony-stimulating factors (G-CSF) for prevention of FN, but guidance is unclear regarding use of short- vs long-acting G-CSF (e.g., filgrastim vs pegfilgrastim/lipegfilgrastim, respectively). An international panel of experts convened to develop guidance on appropriate use of pegfilgrastim for prevention of chemotherapy-induced FN. Methods Guidance recommendations were developed following a literature review, survey, evaluation of current practice, and an expert meeting. Consensus was established using an anonymous Delphi-based approach. Results Guidance recommendations for prevention of treatment-associated FN were as follows: for treatment with curative intent, maintenance of dose intensity using G-CSF to prevent dose delays/reduction should be standard of care; for treatment-associated FN risk ≥ 20%, short-acting G-CSF/pegfilgrastim should be given from cycle 1 onwards; and for treatment-associated FN risk

The US Patient Protection and Affordable Care Act (ACA) aims to expand health care coverage, contain costs, and improve health care quality. Accessibility and affordability of innovative biopharmaceuticals are important to the success of the ACA. As it is substantially more difficult to manufacture them compared with small-molecule drugs, many of which have generic alternatives, biologics may increase drug costs. However, biologics offer demonstrated improvements in patient care that can reduce expensive interventions, thus lowering net health care costs. Biosimilars, which are highly similar to their reference biologics, cost less than the originators, potentially increasing access through reduced prescription drug costs while providing equivalent therapeutic results. This review evaluates 1) the progress made toward enacting health care reform since the passage of the ACA and 2) the role of biosimilars, including the potential impact of expanded biosimilar use on access, health care costs, patient management, and outcomes. Barriers to biosimilar adoption in the USA are noted, including low awareness and financial disincentives relating to reimbursement. The evaluated evidence suggests that the ACA has partly achieved some of its aims; however, the opportunity remains to transform health care to fully achieve reform. Although the future is uncertain, increased use of biosimilars in the US health care system could help achieve expanded access, control costs, and improve the quality of care.

Summary The combination of bendamustine, bortezomib and dexamethasone (BBD) was evaluated as a first-line therapy for multiple myeloma. The original treatment regimen of bendamustine 80 mg/m2, days 1, 4; bortezomib 1·3 mg/m2, days 1, 4, 8, 11; dexamethasone 40 mg, days 1, 2, 3, 4 on a 28-day cycle (up to 8 cycles) was efficacious but determined relatively toxic in an interim analysis. The regimen was amended to bendamustine 80 mg/m2, days 1, 2; bortezomib 1·3 mg/m2, days 1, 8, 15; dexamethasone 20 mg, days 1, 2, 8, 9, 15, 16 every 28 days (up to 8 cycles), then maintenance 1·3 mg/m2 IV bortezomib every 2 weeks. Fifty-nine patients were enrolled. Primary endpoint was complete response (CR) rate. The original schema was given for a median of 7 cycles (range 1–8); modified schema was given for a median of 8 cycles (range 1-8) plus maintenance. Overall response was 91%, CR was 9%. Median follow-up was 19·1 months; median progression-free survival was 11·1 months and 18·9 months on the original and modified regimens, respectively. The most common Grade 3/4 adverse events were fatigue and neuropathy. The combination of BBD is tolerable and efficacious in this patient population. Modifications to decrease intensity but increase duration translated to better outcomes.

Idelalisib, a first-in-class oral inhibitor of phosphatidylinositol-3-kinase δ, has shown considerable antitumor activity as a monotherapy in recurrent indolent non-Hodgkin lymphoma (iNHL). To evaluate the safety and activity of idelalisib in combination with immunotherapy, chemotherapy, or both, 79 patients with relapsed/refractory iNHL were enrolled based on investigator preference in 3 treatment groups. Patients received continuous idelalisib in combination with (1) rituximab (IR; 375 mg/m2 weekly × 8 doses), (2) bendamustine (IB; 90 mg/m2 per day × 2, for 6 cycles), or (3) both bendamustine and rituximab at aforementioned doses (IBR; monthly × 6 cycles). Patients had a median age of 61 years, a median of 3 prior therapies, and 46% had refractory disease. The overall response rate was 75% (22% complete response) for IR, 88% (36%) for IB, and 79% (43%) for IBR. The median progression-free survival was 37.1 months overall: 29.7 months for IR, 32.8 for IB, and 37.1 months for IBR. The median duration of response was 28.6 months in the IR group and has not been reached in the IB and IBR groups. The most common grade ≥3 adverse events and laboratory abnormalities were neutropenia (41%), pneumonia (19%), transaminase elevations (16%), diarrhea/colitis (15%), and rash (9%). The safety and efficacy reflected in these early data, however, stand in contrast with later observations of significant toxicity in subsequent phase 3 trials in frontline chronic lymphocytic leukemia and less heavily pretreated iNHL patients. Our findings highlight the limitations of phase 1 trial data in the assessment of new regimens. This trial was registered at www.clinicaltrials.gov as #NCT01088048 (an extension study was registered at www.clinicaltrials.gov as #NCT01090414).

In the phase 3 ENDEAVOR study, carfilzomib-dexamethasone (Kd) improved survival over bortezomib-dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM), regardless of baseline renal function. This real-world study compared renal response in patients with RRMM (1-3 prior lines) and renal impairment (estimated glomerular filtration rate ≤50 mL/min) treated with Kd vs Vd. Electronic medical records data from the Oncology Services Comprehensive Electronic Records database were assessed (from January 2012 through February 2018). Time to renal response (defined according to International Myeloma Working Group criteria) was evaluated using the Kaplan-Meier method and log-rank test. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for renal overall response (ROR) and renal complete response (RCR) using Cox proportional hazard models adjusted for baseline covariates. Included were 543 Kd-treated and 1005 Vd-treated patients. In line 2 (2L), compared with Vd, Kd achieved significantly higher ROR (51.4% vs 39.6%; P < .0001) and RCR (26.6% vs 22.2%; P = .0229). After baseline covariate adjustment, 2L patients receiving Kd vs Vd were 45% more likely to achieve ROR (IRR, 1.45; 95% CI, 1.18-1.78), and 68% were more likely to achieve RCR (IRR, 1.68; 95% CI, 1.24-2.28). The renal response benefit with Kd remained consistent in 2L to line 4 (4L). In a combined analysis of patients receiving Kd and Vd (2L and 2L-4L), renal responders had longer overall survival and time to next treatment than renal nonresponders. These results demonstrate improved real-world effectiveness of Kd over Vd in RRMM renal rescue, and the positive association between renal response and improved survival.

Background Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation). Preclinically, trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity. Patients and methods This was a phase Ib (open-label, dose-finding) and phase II (randomized, double-blind placebo-controlled) study of the safety, efficacy and PK of trilaciclib in combination with etoposide/carboplatin (E/P) therapy for treatment-naive extensive-stage small-cell lung cancer patients. Patients received trilaciclib or placebo before E/P on days 1–3 of each cycle. Select end points were prespecified to assess the effect of trilaciclib on myelosuppression and antitumor efficacy. Results A total of 122 patients were enrolled, with 19 patients in part 1 and 75 patients in part 2 receiving study drug. Improvements were seen with trilaciclib in neutrophil, RBC (red blood cell) and lymphocyte measures. Safety on trilaciclib+E/P was improved with fewer ≥G3 adverse events (AEs) in trilaciclib (50%) versus placebo (83.8%), primarily due to less hematological toxicity. No trilaciclib-related ≥G3 AEs occurred. Antitumor efficacy assessment for trilaciclib versus placebo, respectively, showed: ORR (66.7% versus 56.8%, P = 0.3831); median PFS [6.2 versus 5.0 m; hazard ratio (HR) 0.71; P = 0.1695]; and OS (10.9 versus 10.6 m; HR 0.87; P = 0.6107). Conclusion Trilaciclib demonstrated an improvement in the patient's tolerability of chemotherapy as shown by myelopreservation across multiple hematopoietic lineages resulting in fewer supportive care interventions and dose reductions, improved safety profile, and no detriment to antitumor efficacy. These data demonstrate strong proof-of-concept for trilaciclib's myelopreservation benefits. Clinical Trail number NCT02499770.

STUDY OBJECTIVE Iron deficiency anemia is the most common form of anemia, and parenteral iron therapy is necessary in select patients. The objective of this analysis was to assess the impact of initial complete parenteral iron repletion on serum hemoglobin (Hgb) level normalization and on health care resource utilization in real-world practice. DESIGN Retrospective observational study. DATA SOURCE Decision Resources Group Real-World Data Repository (United States databases). PATIENTS A total of 2966 patients who had a baseline Hgb level below normal (

Oprozomib is an oral proteasome inhibitor with activity in multiple myeloma (MM). Our phase 1b/2 study examined the safety and efficacy of oprozomib with dexamethasone in patients with relapsed and refractory MM. Oprozomib was administered with a 5/14 or 2/7 schedule with dexamethasone. Phase 1b primary objectives were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of oprozomib; phase 2 primary objectives were to determine overall response rate (ORR) and safety/tolerability of the RP2D. Between July 2, 2013, and August 29, 2016, data were available on 65 enrolled patients (5/14 schedule, n = 19; 2/7 schedule, n = 46). In phase 1b, MTD was 180 mg (5/14 schedule) and not reached (2/7 schedule); RP2D was 300 mg (2/7 schedule). In phases 1b and 2, ORR across dosing cohorts (210–330 mg) for the 2/7 schedule was 58.7% overall and 46.4% for bortezomib-refractory patients (n = 28). All patients reported ≥1 treatment-emergent adverse event (AE); the most common AEs were gastrointestinal. Grade ≥3 AEs occurred in 78.9% and 82.6% of patients on the 5/14 and 2/7 schedules, respectively. The oprozomib and dexamethasone combination has encouraging activity and could be an important MM therapy if gastrointestinal tolerability is improved.

Introduction Ruxolitinib (RUX) is an FDA-approved oral, selective inhibitor of Janus kinase (JAK) 1/2 for the treatment of patients with intermediate or high-risk myelofibrosis and polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. Preclinical studies from our laboratory have demonstrated that RUX in combination with dexamethasone shows marked anti-myeloma effects both in vitro and in vivo. Specifically, RUX blocks expression of Mucin 1 whose function is linked to lenalidomide (LEN) resistance and down-regulates PD-L1 and PD-L2 expression and reduces tumor stimulatory M2 macrophage polarization in multiple myeloma (MM) bone marrow. Recently published results from a Phase 1 trial for 28 heavily previously treated MM patients administered RUX, LEN and methylprednisolone (MP) demonstrated that the therapy was well tolerated and RUX overcame refractoriness to LEN and steroids (Berenson et al., Clin Cancer Res. 2020). The clinical and overall response rates were 46% and 28%, respectively, and all 12 responding patients were refractory to LEN. To further evaluate whether RUX and steroids without LEN demonstrate clinical activity and its tolerability in the same patient population, an ongoing Phase I trial was expanded to also include a cohort of patients treated with this two-drug combination (NCT03110822). Methods MM patients must have failed > 3 prior regimens and have been exposed to a proteasome inhibitor and LEN. Patients were treated orally (PO) with 15 mg RUX twice daily on days 1-28 of a 28-day cycle and 40 mg MP every other day. The treatment of this two-drug combination was continued until disease progression (PD). Once PD was confirmed, LEN at 10 mg PO daily on days 1-21 of a 28-day cycle was added to the regimen. Primary endpoints were safety, clinical benefit rate (CBR) and overall response rate (ORR). Results As of July 25, 2020, 16 of the planned 29 patients have been enrolled, and 15 patients have completed at least 1 full cycle of therapy; and, thus, were evaluable for efficacy. The median age was 64 years (range, 46-77), and 9 (60%) were male. Patients received a median of 4 (range, 3-10) prior treatments including LEN and steroids to which they were all refractory. Of the 15 evaluable patients treated with RUX and steroids, the CBR and ORR were 53% (n=8) and 33% (n=5), respectively. With a median follow-up of 4.7 months, the median duration of response was 3.5 months (range, 1-11+). Five and 2 patients showed stable disease and progressive disease, respectively. Notably, all 8 responding patients were refractory to LEN (i.e. progressed while on or within 8 weeks of last dosage). Of 6 patients who had progressed on the two-drug combination and had LEN added to their regimen, 3 patients responded (2 MR and 1 PR). Four patients experienced SAEs including sepsis (7%), group B strep sepsis with neutropenic fever and nausea (7%), pneumonia and pneumothorax (7%), thrombocytopenia (7%), and hyperglycemia (7%). Two patients died (one each from pneumonia and progressive disease). Conclusions This ongoing phase 1 trial is the first study reporting clinical activity of the JAK inhibitor RUX with steroids for MM. These results demonstrate that RUX with only steroids is also well tolerated and shows promising efficacy for treating heavily previously treated MM patients. Because of this, additional studies are being conducted with higher doses of RUX in combination with MP for this patient population. Disclosures Berenson: Takeda: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Incyte: Honoraria, Patents & Royalties: OncoTracker, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Swift:Jassen: Consultancy, Honoraria, Speakers Bureau; bristol myers squibb: Consultancy, Honoraria, Speakers Bureau; Amgent: Consultancy, Honoraria, Speakers Bureau. Boccia:Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Rigel: Consultancy, Honoraria, Research Funding, Speakers Bureau. OffLabel Disclosure: Ruxolitinib and steroids only for treatment patients with Multiple Myeloma

Outcomes in older patients with Hodgkin lymphoma (HL) tend to be poor following conventional chemotherapy regimens. Treatment-related toxicity is significant and comorbidities often limit therapeutic options. This phase 2, open-label study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, as frontline therapy in 27 HL patients aged ≥60 years. The objective response rate (ORR) was 92%, with 73% achieving complete remission. All patients achieved stable disease or better, and had decreased tumor volume following treatment. At the time of this analysis, the median duration of objective response for efficacy-evaluable patients (N = 26) was 9.1 months (range, 2.8 to 20.9+ months), median progression-free survival was 10.5 months (range, 2.6+ to 22.3+ months), and median overall survival had not been reached (range, 4.6+ to 24.9+ months). The observed adverse events (AEs) were generally consistent with the known safety profile of brentuximab vedotin. The most common AEs were peripheral sensory neuropathy (78%), fatigue (44%), and nausea (44%), and were ≤ grade 2 for most patients. The incidence of grade 3 peripheral neuropathy events was relatively high (30% overall), particularly among patients with the known risk factors of diabetes and/or hypothyroidism (46% vs 14% for those without). However, these risk factors were not associated with delayed time to resolution/improvement of peripheral neuropathy. Preliminary data showed no substantial age-related changes in brentuximab vedotin pharmacokinetics. Brentuximab vedotin monotherapy may provide a frontline treatment option for older patients who cannot tolerate conventional combination chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806.

Context: US MM-6 is investigating iCT from parenteral bortezomib-based induction to all-oral IRd in the diverse US community MM population, aiming to increase proteasome inhibitor (PI)-based treatment adherence/duration while maintaining quality of life and further improving patient outcomes. Objective: Analysis by patient age for the first 84 patients enrolled. Setting: Non-transplant-eligible newly-diagnosed MM patients with ≥stable disease after 3 cycles of bortezomib-based therapy are being enrolled across 22 US community sites to receive IRd for up to 39 28-day cycles or until progression/toxicity. Main outcome measures: Progression-free survival (not reported, data immature; enrollment ongoing). Results: At data cut-off, 47 and 37 patients aged Conclusions: This initial analysis of US MM-6 data by age suggests that by utilizing an iCT approach, long-term PI-based treatment with IRd may be feasible and tolerable in both older and younger patients, and may offer real-world patients the same improved efficacy obtained with long-term proteasome inhibition in clinical studies.

e19332 Background: US MM-6 is investigating iCT from parenteral V-based induction to all-oral I-lenalidomide-dexamethasone (IRd) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence/duration while maintaining quality of life (QoL) & further improving outcomes in the diverse US community population. Methods: 21 US community sites, including VA hospitals, are enrolling non-transplant-eligible newly diagnosed MM pts with ≥stable disease after 3 cycles of V-based therapy to receive IRd. Pts use mobile & digital devices to collect actigraphy (activity/sleep) data, complete QoL & treatment satisfaction questionnaires, & self-report medication adherence. Primary endpoint: progression-free survival (PFS); key secondary endpoints include: response rates & duration of therapy. Results: As of Nov 18, 2019, 84 pts had been treated (median age 73 [range 49–90] yrs; 44% ≥75 yrs; 49% male; 15% black/African American; 10% Hispanic/Latino; 35% International Staging System stage III disease; 42% lytic bone disease). Comorbidities included hypertension (57%), anemia (44%), fatigue (43%), & peripheral neuropathy (13%). 85% of pts were receiving VRd at the time of iCT. 62% of pts are still on therapy & enrollment is ongoing. After initiating iCT, ≥complete response (CR) rate increased from 4% to 26% (Table). At 8 mos median follow-up, 6 pts had progressed & there were 2 on-study deaths. The 12-mo PFS rate was 86% (95% CI, 73–93) from the start of V-based regimen & from the start of IRd. During IRd treatment, 92% of pts had treatment-emergent adverse events (TEAEs) (48% grade [G] ≥3). G3 TEAEs (≥5% of pts) were diarrhea (7%), pneumonia (6%), syncope (6%), & anemia (5%). TEAEs led to study drug discontinuation in 7% of pts; 36% had serious TEAEs. I/R/d dose was adjusted due to AEs in 39%/39%/29% of pts. Medication adherence (cycles 1–5) was ‘excellent’/‘very good’ in ≥78% of pts reporting adherence. QoL/treatment satisfaction were maintained in pts completing questionnaires. Actigraphy data showed normal activity levels & sleep durations. Conclusions: US MM-6 pts are representative of the RW US MM population & results show that iCT to an oral PI may permit prolonged PI-based therapy with promising efficacy & without impacting pts’ QoL or treatment satisfaction. Clinical trial information: NCT03173092 . [Table: see text]

TPS268 Background: Docetaxel IV and prednisone is a standard of care in mCRPC with demonstrated overall survival benefit. ModraDoc006 is a novel oral tablet formulation of docetaxel and to enhance bioavailability, it is co-administered with ritonavir (/r), an inhibitor of cytochrome p450 3A4 and P-glycoprotein. The oral combination, denoted as ModraDoc006/r, could be preferable due to patient convenience and elimination of infusion reactions and prophylactic steroids administration. Due to its weekly administration and exposure levels, increased efficacy may be demonstrated. Methods: The study is an open label 1:1 randomized phase 2b trial of ModraDoc006/r bi-daily QW versus docetaxel IV 75 mg/m2 Q3W. Thirty (30) mg ModraDoc006 combined with 200 mg /r in morning and 20 mg ModraDoc006 with 100 mg /r in evening is administered on days 1, 8 and 15 of a 21 day cycle. Safety and preliminary efficacy of ModraDoc006/r have been established in a phase Ib trial in mCRPC pts. All patients will receive 5 mg oral prednisone twice daily. Treatment is continued until progression, unacceptable toxicity or patient wish. mCRPC pts with measurable disease per RECIST 1.1, suitable for docetaxel therapy, are eligible. No prior treatment with taxanes is allowed. Primary objective is objective response rate (ORR) as assessed by investigators. Secondary objectives include PSA response, PSA-PFS, time to skeletal related events and progression, duration of response, disease control rate and safety assessments. Patient reported outcomes and health-related quality of life will be captured with treatment satisfaction and FACT-P questionnaires. It is expected that ModraDoc006/r will be at least as effective as docetaxel IV. A sample size of 50 evaluable pts per arm will evaluate an estimated ORR of 25% in each arm, with a 5% two-sided alpha and power of 83.7%. Conclusions: ModraDoc006/r represents an advance in prostate cancer therapeutics with convenience of oral administration, reduced myelosuppressive toxicity and potential improved efficacy over IV docetaxel. Clinical trial information: NCT04028388.

Aim: Fosaprepitant, an intravenous neurokinin-1 receptor antagonist for chemotherapy-induced nausea and vomiting, contains polysorbate 80, which is associated with infusion-site adverse events (ISAEs) and hypersensitivity systemic reactions (HSRs). This study investigated ISAEs/HSRs following fosaprepitant with anthracycline-containing chemotherapy. Patients & methods: This retrospective chart review noted ISAEs/HSRs following the anthracycline doxorubicin+cyclophosphamide and a three-drug fosaprepitant regimen, via peripheral line. Results: 35/127 patients (28%) developed ISAEs/HSRs with chemotherapy and antiemetic therapy: 32 developed 137 individual ISAEs, primarily erythema, pain and catheter-site swelling; 16 developed 50 individual HSRs, primarily edema/swelling, erythema or dermatitis (no anaphylaxis). Conclusion: Fosaprepitant is associated with a significant ISAE/HSR rate following anthracycline-containing chemotherapy via peripheral line. Polysorbate 80-free intravenous neurokinin-1 receptor antagonist may provide a safer chemotherapy-induced nausea and vomiting prophylaxis option.

Introduction Parenteral iron therapy is often necessary for patients with iron deficiency anemia who cannot tolerate or are nonresponsive to oral iron. Parenteral iron therapy is also used in patients with chronic diseases when oral iron is poorly absorbed or when rapid iron repletion is desirable. Several parenteral iron therapies are currently available in the US. They vary in the amount of iron dose per administration and the number of infusions required to achieve complete iron repletion. The objective of this analysis was to evaluate complete repletion of iron deficit and its effect on the likelihood of serum hemogloblin (Hgb) normalization among patients receiving various parenteral iron therapies in real world clinical practice. Methods Data was obtained from the Decision Resources Group (DRG) Real World Evidence US Data Repository. Patients (≥18 years) who were treated with parenteral iron therapy from 3/1/2015-2/28/2017 were included. Patients were required to have their most recent baseline Hgb level recorded Iron deficit was calculated using the modified Ganzoni equation. The proportion of patients receiving parenteral iron dose required for complete repletion during the 3 weeks after index date, and the proportion of patients achieving normalized Hgb levels within 1 year after index date were summarized for patients receiving ferric carboxymaltose (FCM), ferumoxytol (FM) and other parenteral iron products (OTH). Multivariable logistic regression was used to assess the likelihood of complete iron repletion within 3 weeks of index date while controlling for gender, age, comorbidities, prescription oral iron use and iron deficit level. The likelihood of Hgb normalization within 1 year of index date was assessed using multivariable logistic regression while controlling for gender, age, comorbidities, prescription oral iron use, baseline Hgb and if the patient received the complete iron repletion dose within 3 weeks of index date. Results A total of 2,966 patients were included (female [68.2%], ≥65 years [58.4%]; CKD [60.1%], congestive heart failure [50.1%], IBD [64.4%], and cancer [59.5%]). Most (95%) patients did not receive prescription oral iron therapy within 3 months before or after index date. Iron sucrose was the most commonly used parenteral therapy (46.2%), followed by FCM (23.1%), FM (13.7%), iron dextran (13.6%), and sodium ferric gluconate complex in sucrose (3.4%). Mean (SD) iron deficit in mg was 966 (303) for FCM, 1007 (317) for FM and 1011 (313) for OTH patients. FCM had the highest proportion of patients received the full iron repletion dose within the 3 weeks after index date (73.1%), followed by FM (41.4%) and OTH (18.0%). Mean (SD) total iron dose in mg received by FCM, FM and OTH patients within 3 weeks of index date was 1277.1 (446.9), 842.5 (357.6), and 534.2 (584.8), respectively. The proportion of patients who had normalized Hgb within 1 year of index date was 66.6%, 40% and 51.9% for FCM, FM and OTH, respectively. Patients treated with FCM were significantly more likely to have received their full repletion dose within 3 weeks of index date than patients treated with FM [adjusted odds ratio (AOR)] (95% CI) = 5.10 (3.66, 7.11)] or OTH [AOR (95% CI) = 17.46 (13.59, 22.42)] after adjusting for differences in iron deficit level and other covariates. Patients treated with FM also had higher likelihood of receiving full repletion dose within 3 weeks compared to OTH [AOR (95% CI) = 3.71 (2.82, 4.88)]. After adjusting for full repletion dose and other covariates, patients treated with FCM were significantly more likely to have normalized Hgb within 1 year of index date than patients treated with FM [AOR (95% CI) = 1.88 (1.38, 2.56) or OTH [AOR (95% CI) = 1.40 (1.11, 1.77). However, patients treated with FM had lower likelihood to have normalized Hgb within 1 year of index date than patients treated with OTH [AOR (95% CI) = 0.69 (0.53, 0.89)]. Conclusion The results of this analysis suggest that the choice of iron replacement product may affect the likelihood of Hgb normalization for some patients in real world practice. Disclosures Kwong: Daiichi Sankyo, Inc.: Employment. Boccia:Bristol Myers Squibb: Consultancy, Speakers Bureau; SecuraBio: Consultancy; Rigel: Speakers Bureau; Daiichi Sankyo, Inc.: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; AMAG: Consultancy.

Background: Iron deficiency anemia (IDA) is common in cancer patients due to blood loss and inflammation. Intravenous (IV) iron is commonly used in these patients as monotherapy or as an adjunct to erythropoiesis-stimulating agents as many do not tolerate, or adequately respond to oral iron. Over the last decade it has become apparent that hypophosphatemia may occur following some IV iron formulations. While initially considered a transient benign laboratory finding, a growing number of case reports have described treatment-emergent hypophosphatemia following IV iron administration as a safety consideration, especially in patients with normal renal function. Although hypophosphatemia may have clinical consequences, its diagnosis may be missed in the clinic due to initial nonspecific symptomatic presentation e.g., generalized weakness and fatigue. Patients with cancer, already at additional risk for hypophosphatemia for various reasons, including, bone metastasis, bone-modifying agents, and other drugs, might be at a higher risk for hypophosphatemia. Objective: To evaluate the effects of IV iron treatment on the incidence of hypophosphatemia in the subgroup of patients with cancer who participated in a randomized, double-blind Phase 3 clinical trial (NCT02694978) that compared two IV iron preparations for the treatment of adults with IDA of any etiology (excluding dialysis-dependent CKD) and a history of unsatisfactory response to, or intolerance of oral iron. Methods: Randomization was 1:1 to ferumoxytol (FER), administered as two 510 mg doses, or ferric carboxymaltose (FCM), administered as two 750 mg doses both delivered as an IV infusion over at least 15 minutes on days 1 and 8. Serum phosphate and other clinical laboratory values were measured at baseline, days 8 (prior to dose 2), 15, and 35. Data from patients with a recent or coincident diagnosis of cancer were extracted for post-hoc analyses. Within-group changes from baseline in phosphate levels were analyzed with paired t-test; between-group differences were analyzed using ANCOVA adjusted for baseline value. The overall incidence and visit-specific rates of severe hypophosphatemia (CTCAE Grade 3; Results: The overall study safety population of 1,997 randomized patients who received any amount of study drug included 153 patients with cancer (78 FCM, 73 FER, 62.1% female; mean age 65.5 ± 13.2 years, mean baseline Hgb 10.5 ± 1.3g/dL, GFR 69.9 ± 32.4 mL/min/m2). Baseline serum phosphate was ≥2.4 mg/dL for all patients in the cancer subgroup, and mean values were similar between treatment groups (FCM 3.74 ± 0.53 and FER 3.86 ± 0.81 mg/dL). Mean serum phosphate level in the FCM group decreased significantly at each time-point compared both to baseline and to the FER group (P In a logistic regression model including factors for renal function, severity of anemia, weight, bisphosphonate use, and baseline phosphate level, the only independent predictors of hypophosphatemia were baseline phosphate level (OR 4.3, 95% CI 1.5 to 12.1, for each 1 mg/dL decrease, P=0.006) and treatment with FCM (OR 120.1, 95% CI 12.2 to 1182.1 vs. FER, P Conclusion: Post hoc analyses of data from a Phase 3 clinical trial showed that mean serum phosphate decreased significantly in anemic cancer patients following FCM, but not FER, starting as soon as 8 days following the first 750mg dose, and did not return to baseline level by the end of the study period. This resulted in hypophosphatemia Disclosures Boccia: DSI: Speakers Bureau; Genentech: Speakers Bureau; AMAG: Consultancy; Amgen: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene: Speakers Bureau. Dahl:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership. Strauss:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership.

Introduction. Immune thrombocytopenia (ITP) is characterized by autoantibody-mediated platelet destruction resulting in thrombocytopenia and often at least a degree of bruising and bleeding. Platelet destruction occurs within activated macrophages that signal via spleen tyrosine kinase (SYK) following Fcγ receptor engagement by platelet-bound IgG antibodies. Fostamatinib is a SYK inhibitor, taken orally twice daily with or without food. In the three phase 3 clinical studies (2 randomized, controlled trials and 1 open-label extension study), 145 adults with ITP received fostamatinib. These patients had a median of 3 prior therapies (range 1-13) and a median of 8.4 years (range Methods. The phase 3 trials included patients with persistent or chronic ITP, who had failed ≥1 prior treatment and had ≥3 platelet counts Results. Of 145 patients, 32 (22%) received fostamatinib as second-line therapy. Baseline characteristics of the 32 patients included median age of 50 years (range 20-88), median duration of ITP of 2.7 years, and median platelet count of 21,000/μL. Of these 32 patients, 25 (78%) had an overall platelet response, which compares favorably with the 47% response rate in the 113 patients who received fostamatinib as 3rd line or later therapy. The most commonly reported adverse events (AEs) in the 32 fostamatinib-as-second-line-therapy patients were hypertension, diarrhea, upper respiratory tract infection, nausea, vomiting, elevated liver enzymes, petechiae, and headache. AEs were primarily mild to moderate in severity and resolved or were managed by dose reduction, dose interruption, and/or secondary medication. The type and frequency of AEs in the second-line patients were consistent with that of the overall study population. We also assessed the subgroup of 29 patients with early-stage disease (of whom 11 received fostamatinib as second-line therapy). An overall response to fostamatinib was achieved by 9 of 10 (90%) patients with persistent ITP ( Conclusions. A higher percentage of patients had an overall response to fostamatinib as second-line therapy for ITP (78%) compared with later lines of therapy (47%), and a higher percentage with persistent ITP (90%) responded than those with earlier stage (1-2 years) chronic ITP (57%) or later stage chronic ITP (50%). These data suggest that higher response rates may be seen with the use of fostamatinib as second-line therapy for ITP and in persistent ITP patients as compared with later lines of therapy and later stage ITP. Disclosures Boccia: SecuraBio: Consultancy; AMAG: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Rigel: Speakers Bureau; Daiichi Sankyo, Inc.: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Boxer:Takeda: Honoraria, Speakers Bureau; Arizona Oncology: Employment; Incyte: Speakers Bureau; Best Doctors: Consultancy; Abbvie: Honoraria, Speakers Bureau; Gerson Lerman: Consultancy; Rigel: Speakers Bureau. Ghanima:Bayer: Honoraria, Research Funding; Pfizer/BMS: Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Hill:Bioverativ, a Sanofi company: Honoraria; Apellis: Honoraria; Novartis: Speakers Bureau; Alexion: Research Funding. Sholzberg:Amgen: Honoraria, Research Funding; Novartis: Honoraria. Tarantino:Michael Tarantino, MD SC: Other: President, Owner- Private Practice ; Magellan Healthcare: Consultancy; Roche: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Grifols: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bleeding and Clotting Disorders Institute: Employment. Kreychman:Rigel: Employment, Equity Ownership. Numerof:Rigel: Employment, Equity Ownership. Olender:Rigel: Employment, Equity Ownership. Todd:Rigel: Employment, Equity Ownership. Tong:Rigel: Employment, Equity Ownership. Duliege:Rigel: Employment, Equity Ownership. Cooper:Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bussel:Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Momenta Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kezar Life Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tranquil: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; 3S Bio: Speakers Bureau; Physician Education Resource: Speakers Bureau; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; RallyBio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; UCB: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Fostamatinib is a tyrosine kinase (SYK) inhibitor for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The use of fostamatinib in other diseases is off-label.

Background US MM-6 is a US community-based study that investigates the transition from a parenteral (btz) to an oral (ixazomib) proteasome inhibitor (PI) in NDMM to increase PI-based treatment duration and adherence, maintain QoL, and improve outcomes. Here, we report on the novel, RW aspects of the study including the use of digital devices/wearables to evaluate QoL, medication adherence, and actigraphy (average steps and sleep time/ day) in a community oncology setting, for the first 55 enrolled pts. Methods NDMM pts who are transplant-ineligible or transplant-delayed >24 mos and have ≥stable disease after 3 cycles of btz-based induction are being enrolled at 23 community sites. Pts receive IRd (ixazomib 4 mg, d 1, 8, 15; lenalidomide 25 mg, d 1-21; dexamethasone 40 mg [20 mg for pts aged >75 yrs], d 1, 8, 15, 22; each 28-d cycle) for up to 26 x 28-d cycles or until progression/toxicity. The primary endpoint is progression-free survival. Novel secondary and exploratory endpoints are included to capture pts' experience in the RW community setting. Electronic pt-reported outcomes (ePROs) are used to assess medication adherence and QoL, as measured by the European Organization for Research and Treatment of Cancer (EORTC) Core QoL Questionnaire (QLQ-C30), EORTC QoL Questionnaire-Multiple Myeloma Module (QLQ-MY20) for peripheral neuropathy (PN), and the Treatment Satisfaction Questionnaire for Medication (TSQM-9). Pts use wearable digital devices/smartphones to complete a monthly medication adherence survey and record actigraphy. Results At the data cutoff of April 1 2019, 55 pts had been enrolled at 16 sites in the US; 40 were still undergoing treatment. Females comprised 53% of pts, 13% were of Hispanic/Latino ethnicity, and 13% were black/African American. Pt/disease characteristics revealed a comorbid, difficult-to-treat RW population: median age was 72 yrs (35% 65-75 yrs; 42% ≥75 yrs); 40% had International Staging System stage III disease, and 42% had lytic bone disease. Most common comorbidities at study start were hypertension (51%), anemia (44%), fatigue (42%), renal and urinary disorders (36%), gastroesophageal reflux disease (31%), and cardiac disorders (27%). Prior to IRd treatment, the 3-cycle btz-based induction required adjusting in 11 (20%) pts: 38 (69%) pts started induction with btz-lenalidomide-dexamethasone (VRd) (1 had only 1 cycle documented, 1 de-escalated to Vd), 7 (13%) started on btz-cyclophosphomide-dexamethasone (VCd) (2 had only 1 cycle documented), 4 (7%) started on Vd (3 escalated to VRd), and 2 (4%) started on VCRd but de-escalated to VCd/VRd after 1 cycle; 3 (5%) pts received VR only (Figure). Average compliance with completing issued ePRO questionnaires during IRd treatment was 96%, and ≥87% in all cycles (61 pts; data cutoff July 8, 2019), revealing the feasibility of ePRO collection in community pts, most of whom were elderly. During IRd treatment, there was a trend toward improved treatment satisfaction and QoL, with no increase in PN symptoms (Figure). Mean change (95% CI) from baseline on EORTC QLQ-C30 score was 5.12 (-13.79-24.02) by cycle 5 (n=13), 15.47 (-16.45-47.39) by cycle 8 (n=7), and -4.18 (-21.29-12.94) by cycle 12 (n=5). Mean change (95% CI) from baseline on TSQM-9, subscale 'effectiveness', was 7.54 (-1.84-16.91) by cycle 5 (n=14), and 11.13 (-12.82-35.08) by cycle 12 (n=3), with similar patterns for subscales 'convenience' and 'global satisfaction' (Figure). Mean change from baseline on EORTC QLQ-MY20, PN component, was between 0.0-2.0 throughout all cycles. Patients recorded their monthly medication adherence for the previous 4 weeks; 81% of evaluable pts (n=32) in cycle 1, 81% in cycle 2 (n=27), 77% in cycle 3 (n=22), 96% in cycle 4 (n=24), and 94% in cycle 5 (n=18) (n Analysis of actigraphy data for 24 pts (2086 compliant days [≥12h of data]) (Figure) revealed normal levels of activity (Tudor-Locke 2011) and sleep durations (Coleman 2011). Updated actigraphy data will be presented. Conclusions Preliminary ePRO and actigraphy data from this RW community study suggest that long-term treatment with all-oral IRd has no impact on health-related QoL or on pts' lifestyle. High ePRO compliance indicates that RW studies using wearable electronic data collection devices are feasible in this mostly elderly, comorbid population, and may have a positive impact on medication adherence. Disclosures Noga: Takeda: Employment. Rifkin:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Birhiray:Alexion: Consultancy; Bayer: Honoraria; Helsin: Honoraria; Sanofi Oncology: Speakers Bureau; Puma: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Incyte: Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau; Amgen: Honoraria, Speakers Bureau; BMS: Speakers Bureau; Tessaro: Speakers Bureau; Exelexis: Speakers Bureau; Kite Pharma: Honoraria; Clovis Oncology: Speakers Bureau; Lilly: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene: Honoraria; Takeda: Research Funding, Speakers Bureau; Genomic Health: Speakers Bureau; Jansen Bioncology: Consultancy, Speakers Bureau; Seattle Genetics: Honoraria; Abbvie: Consultancy, Honoraria; Coheris: Honoraria. Lyons:Texas Oncology: Equity Ownership; Amgen: Consultancy; McKesson: Other: Leadership. Whidden:Takeda: Employment. Schlossman:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Wang:Millennium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Boccia:Celgene: Speakers Bureau; Genentech: Speakers Bureau; Amgen: Speakers Bureau; AstraZeneca: Speakers Bureau; AMAG: Consultancy; DSI: Speakers Bureau.

Introduction Ruxolitinib (RUX) is an FDA-approved oral, selective inhibitor of Janus kinase (JAK) 1/2 for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea or intermediate or high-risk myelofibrosis (MF). Preclinical studies from our laboratory have demonstrated that RUX in combination with the immunomodulatory agent lenalidomide (LEN) and dexamethasone shows marked anti-myeloma effects both in vitro and in vivo. Furthermore, MUC1 (Mucin 1) is responsible for LEN resistance in MM cells, and RUX blocks its expression in multiple myeloma (MM) cells. Thus, RUX may restore sensitivity to LEN. RUX also downregulates PD-L1 and PD-L2 expression on MM cells and reduces tumor stimulatory M2 macrophage polarization in MM bone marrow. Therefore, a phase 1 trial was conducted to determine the safety and efficacy of RUX in combination with LEN and the steroid methylprednisolone (MP) for relapsed/refractory (RR) MM patients who had previously been treated with LEN/steroids and a proteasome inhibitor (PI) and showed progressive disease at study entry. Methods A traditional 3+3 dose escalation design was used to enroll subjects in four cohorts with planned total enrollment to be 49 patients. Subjects received RUX twice daily continuously, LEN daily on d1-21 of a 28-d cycle and MP orally every other day. In DL0, patients received RUX 5 mg, LEN 5 mg, and MP 40 mg. In DL+1 and +2, both doses of LEN and MP remained unchanged and RUX was escalated to 10 and 15 mg, respectively. DL+3 escalated LEN to 10 mg with MP unchanged and RUX at 15 mg. Primary endpoints were safety, clinical benefit rate (CBR) and overall response rate (ORR). Results As of March 1, 2019, 43 patients were enrolled, and 40 were evaluable for efficacy. The median age was 65 years (range, 46-81), and 25 (58%) were male. Patients received a median of 6 prior treatments including LEN and steroids to which they were all refractory. No DLTs occurred, and DL+3 was expanded. Among all 40 evaluable patients, the CBR and ORR were 47% and 37%, respectively (1 CR, 4 VGPR, 10 PR and 4 MR), and 16 and 5 patients showed SD and PD. Notably, all 19 patients achieving > MR were refractory to LEN (i.e. progressed while on or within 8 weeks of last dosage). The median PFS for all evaluable patients was 4 months. G3/4 AEs included anemia (16%), sepsis (14%), lymphocytopenia (14%), pneumonia (12%), neutropenia (12%) and hypokalaemia (12%). Most common SAEs included sepsis (14%) and pneumonia (12%). Conclusions This phase 1 trial demonstrates for the first time that a JAK inhibitor, RUX, can overcome refractoriness to LEN and steroids for RRMM patients. This all oral regimen was well tolerated, and reversible Grade 3/4 cytopenias occurred in only a small minority of patients. These promising results are leading to expansion of the current clinical trial to 78 patients, and represent a potential novel therapeutic approach for treating MM. Disclosures Berenson: Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amag: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Amag: Consultancy, Speakers Bureau; Sanofi: Consultancy; Amgen: Consultancy, Speakers Bureau; Sanofi: Consultancy; OncoTracker: Equity Ownership, Other: Officer; OncoTracker: Equity Ownership, Other: Officer; Takeda: Consultancy, Speakers Bureau; Incyte Corporation.: Consultancy, Research Funding; Incyte Corporation.: Consultancy, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Swift:Bristol Mayers Squib: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Jansen: Consultancy, Honoraria. Eades:Celgene: Other: Stock. Boccia:Genentech: Speakers Bureau; DSI: Speakers Bureau; AMAG: Consultancy; AstraZeneca: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau. OffLabel Disclosure: The goal of this clinical trial is to establish ruxolitinib in combination with lenalidomide and methylprednisolone as the therapy for relapse/refractory multiple myeloma patients.

Background: Immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impairment of platelet production, leading to downstream thrombocytopenia, a predisposition to bleeding, and adverse impact on patient quality of life. Unmet needs in relapsed or refractory ITP are to improve remission rates and durability through targeting underlying disease mechanisms. PRN1008 is an oral, reversible, covalent inhibitor of Bruton tyrosine kinase (BTK) that modulates immune-mediated processes in ITP. Preclinical PRN1008 data showed inhibition of B-cell receptor-mediated activation of human B cells, Fc receptor (Fc-gamma and Fc-epsilon)-mediated activation of immune cells, and dose-dependent reduction in platelet loss in a mouse ITP model. In platelets from normal healthy volunteer and ITP patients, clinically-relevant concentrations of PRN1008 showed no platelet aggregation or interference with other platelet agonists, in contrast to ibrutinib (Langrish et al. ASH 2017:1052). Methods: This is an ongoing open-label, adaptive, intra-patient dose-escalation, phase I/II study of PRN1008 in adult patients with relapsed or refractory ITP (primary or secondary) who previously responded to ≥ 1 prior ITP therapy and have no available therapeutic options (NCT03395210). Eligible patients have two platelet counts < 30,000/µL within 15 days prior to treatment. Oral PRN1008 starting doses were 200 mg QD, 400 mg QD, 300 mg BID (total 600 mg daily), and 400 mg BID (total 800 mg daily), with intra-patient dose escalation allowed every 4 weeks (maximum 400 mg BID) as needed for efficacy. Stable doses of concomitant corticosteroids and thrombopoietin-receptor agonists (TPO-RA) are permitted. The primary end point is the proportion of patients with ≥ 2 consecutive platelet counts (separated by ≥ 5 days) of ≥ 50,000/µL and increased by ≥ 20,000/µL from baseline without requiring rescue medication. Results: A total of 21 patients have been enrolled to date at starting doses of 200 mg QD (n=9), 400 mg QD (n=1), 300 mg BID (n=5), and 400 mg BID (n=6). As of 15 July 2019 data cut-off, 11 patients were receiving ongoing treatment, 4 completed the study, and 6 patients withdrew (2 due to patient decision, 2 from non-treatment-related adverse events [AEs], 1 erroneously enrolled, and 1 because of rescue medication use). Patients had a median age of 54 y (range, 30-65), 4 (19%) had a prior splenectomy, 19 (90%) were diagnosed with primary ITP, and 2 (10%) with secondary ITP. Patients had ITP for a median of 8.3 years (range, 0.5-42.4) and had received a median of 4 prior ITP therapies. Median platelet count at study entry was 14,173/µL (range, 2,670-27,000/µL). During the study, 6 (29%) patients received PRN1008 monotherapy; 15 (71%) patients were on ≥ 1 concomitant ITP medication. Related treatment-emergent AEs (TEAEs) were reported by 4 (19%) patients; all were grade 1 or 2. The most frequent related TEAEs were nausea, diarrhea, and abdominal distension. There were no treatment-related bleeding or thrombotic events, and no significant changes in the ITP-BAT bleeding scale between baseline and the last visit. There were no dose limiting toxicities (DLT). Patients had received treatment for a median of 10.1 weeks (range, 0.1-31.0). Overall, 7 (33%) patients achieved the primary endpoint across all doses (Table). Patient responses were improved at the 2 higher doses. In 10 patients who had reached ≥ 12 weeks of treatment, ≥ 50% of patients had platelet counts of ≥ 50,000/µL and ≥ 20,000/µL increases from baseline. Conclusion: Overall, PRN1008 was active in 33% of ITP patients who were refractory to multiple treatments with no alternative therapeutic options. This result was demonstrated despite the limited duration of treatment and including patients at all dose levels. In addition, patients treated for longer periods of time have substantially improved response rates that support continued interest in this ongoing study. The safety profile was tolerable at all studied doses whether given as a monotherapy or with allowed concomitant ITP therapy. Importantly, TEAEs were grade 1 or 2 with no thrombotic events. The dose-escalation portion of the study is complete; enrollment is expanding at the 400 mg BID starting dose for a duration of 24 weeks to further characterize treatment benefit and for continued treatment beyond 24 weeks in patients who have responded. Disclosures Kuter: Dova: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Caremark: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Kezar: Research Funding; Argenx: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria; Principia: Consultancy, Honoraria, Research Funding; Alnylam: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Shinogi: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Protalex: Consultancy, Honoraria, Research Funding; Protalix: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; UCB: Consultancy, Honoraria; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; Zafgen: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Boccia:AstraZeneca: Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; AMAG: Consultancy; Genentech: Speakers Bureau; DSI: Speakers Bureau. Lee:Weill Cornell Medical College: Employment. Tzvetkov:UMHAT Georgi Stranski: Employment; DCC Pleven: Consultancy. Mayer:AOP Orphan Pharmaceuticals AG: Research Funding. Trněný:Abbvie: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy; F. Hoffmann-La Roche: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Kostal:Novartis: Honoraria; AOP: Honoraria; University Hospital in Hradec Kralove, Czech Republic: Employment. Hajek:Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; PharmaMar: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau. McDonald:Bayer: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Bandman:Principia Biopharma: Employment, Equity Ownership, Patents & Royalties: Institutional with Incyte and Portola, no royalties. Burns:Principia BioPharma: Employment. Neale:Principia BioPharma: Employment, Equity Ownership. Thomas:Principia Biopharma: Employment, Equity Ownership; BMS: Equity Ownership; Pfizer: Equity Ownership. Cooper:Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Disclosure: Yes, this was an investigational clinical phase I/II study of PRN1008 in patients with relapsed/refractory ITP. Phase I dose escalation phase is now complete and expanded phase II studies ongoing.

Background PI-based therapy is a standard of care for non-transplant NDMM pts. However, long-term treatment, which is associated with improved outcomes, is often challenging in the RW. This may be due to a number of factors, including the burden of repeated intravenous (IV)/subcutaneous (SC) administration, distance from treatment center, comorbidities, and toxicity (e.g. peripheral neuropathy [PN] with btz). With the aim of increasing PI-based treatment adherence and duration while maintaining quality of life (QoL), the US MM-6 RW, community-based study (NCT03173092) investigates a transition from IV/SC btz-based induction to all-oral ixazomib-based therapy (ixazomib-lenalidomide-dexamethasone, IRd). We report efficacy and safety, plus adherence and electronic pt-reported outcomes (ePRO) compliance data, for the first 55 pts. Methods Non-transplant NDMM pts (transplant-ineligible or transplant delayed >24 mos) with ≥stable disease (SD) after 3 cycles of a btz-based induction are being enrolled at 23 community sites to receive IRd (ixazomib 4 mg, d 1, 8, 15; lenalidomide 25 mg, d 1-21; dexamethasone 40 mg [20 mg in pts aged >75 yrs], d 1, 8, 15, 22) for up to 26 x 28-d cycles or until progression/toxicity. Pts complete ePROs every cycle to assess QoL/treatment satisfaction, and a monthly medication adherence survey via a wearable device/smartphone. The primary endpoint is progression-free survival (PFS); key secondary endpoints include partial (PR), very good partial (VGPR), and complete (CR) response rates, and duration of therapy. Results As of April 1 2019, 55 pts had been enrolled at 16 sites. Median age was 72 (range 49-90) yrs, with 76% classified as elderly (≥65 yrs); 47% were male. Key characteristics of this RW population are summarized in Table 1. Comorbidities/concurrent medical conditions at the start of IRd therapy were extensive and included hypertension (51%), anemia (44%), fatigue (42%), renal and urinary disorders (36%), gastroesophageal reflux disease (31%), cardiac disorders (27%), constipation (27%), nausea (24%), and PN (16%); 91% of pts were receiving concomitant medications. At data cutoff, with 40 (73%) pts remaining on therapy, median duration of PI therapy, including prior btz-based induction, was 6.9 mos (mean 8.4 mos) (Table 2). Median duration of IRd treatment was 4.0 mos (median 5 cycles; mean 5.6 mos, 6.6 cycles), with pts having received up to 17.3 mos (18 cycles) of therapy to date. After 3 cycles of btz-based induction, the ≥VGPR rate was 27%, with 4% ≥CR; overall response rate (ORR) was 62%. With IRd therapy, the ≥VGPR rate was 40%, with 22% ≥CR; ORR was 65% (15% not evaluable). Following transition from btz-based induction to IRd, 21 pts (36%) had deepened responses (18% increase in ≥CR rate), including 3 VGPR to CR, 3 PR to CR, 1 MR to CR, 4 SD to CR, 3 PR to VGPR, 1 SD to VGPR, 5 SD to PR, and 1 SD to MR (Figure). With limited follow-up, and enrollment ongoing, 3 pts had progressed and one had died at data cutoff. The preliminary 6-mo PFS rate (95% CI) was 91% (74-97%) from start of IRd and 96% (84-99%) from start of btz-based induction. Average compliance with completing issued ePRO questionnaires during IRd treatment was 96% (61 pts; data cutoff July 8, 2019). Patients recorded their monthly medication adherence for the previous 4 weeks; 81% of evaluable pts (n=32) in cycle 1, 81% in cycle 2 (n=27), 77% in cycle 3 (n=22), 96% in cycle 4 (n=24), and 94% in cycle 5 (n=18) (n2 pts. AEs led to study drug modification in 47% and discontinuation in 4% of pts; 29% had serious AEs. PN occurred in 25% (4% grade 3) and led to dose modification in 13% of pts. There were no on-study deaths (i.e. occurring Conclusions These preliminary data in mostly elderly, comorbid, NDMM pts treated in the RW, community setting indicate the feasibility, tolerability, and efficacy of transitioning to IRd after 3 cycles of btz-based induction. Toxicities appeared similar to previous ixazomib studies. With 73% of pts remaining on therapy and enrollment continuing, duration of therapy is promising, substantial improvements in response have been seen, and ePRO compliance/ medication adherence is high, indicating the feasibility and value of these evaluations. Disclosures Rifkin: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Noga:Takeda: Employment. Yimer:Amgen: Consultancy; Puma Biotechnology: Equity Ownership; Clovis Oncology: Equity Ownership; Celgene: Honoraria; Seattle Genetics: Honoraria; Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau. Girnius:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Birhiray:Puma: Consultancy, Research Funding, Speakers Bureau; Alexion: Consultancy; Kite Pharma: Honoraria; Bayer: Honoraria; Helsin: Honoraria; Incyte: Research Funding, Speakers Bureau; Seattle Genetics: Honoraria; Pfizer: Speakers Bureau; Abbvie: Consultancy, Honoraria; Celgene: Honoraria; AstraZeneca: Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Sanofi Oncology: Speakers Bureau; Lilly: Speakers Bureau; Genomic Health: Speakers Bureau; Amgen: Honoraria, Speakers Bureau; BMS: Speakers Bureau; Tessaro: Speakers Bureau; Exelexis: Speakers Bureau; Clovis Oncology: Speakers Bureau; Jansen Bioncology: Consultancy, Speakers Bureau; Coheris: Honoraria; Takeda: Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Speakers Bureau. Yasenchak:Seattle Genetics: Consultancy; BMS: Consultancy. Lyons:Texas Oncology: Equity Ownership; Amgen: Consultancy; McKesson: Other: Leadership. Whidden:Takeda: Employment. Schlossman:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Wang:Millennium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Boccia:DSI: Speakers Bureau; AstraZeneca: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Genentech: Speakers Bureau; AMAG: Consultancy.

FcRH5 is a cell surface marker enriched on malignant plasma cells when compared to other hematologic malignancies and normal tissues. DFRF4539A is an anti-FcRH5 antibody-drug conjugated to monomethyl auristatin E (MMAE), a potent anti-mitotic agent. This phase I study assessed safety, tolerability, maximum tolerated dose (MTD), anti-tumor activity, and pharmacokinetics of DFRF4539A in patients with relapsed/refractory multiple myeloma. DFRF4539A was administered at 0.3–2.4 mg/kg every 3 weeks or 0.8–1.1 mg/kg weekly as a single-agent by intravenous infusion to 39 patients. Exposure of total antibody and antibody-conjugate-MMAE analytes was linear across the doses tested. There were 37 (95%) adverse events (AEs), 8 (21%) serious AEs, and 15 (39%) AEs ≥ grade 3. Anemia (n = 10, 26%) was the most common AE considered related to DFRF4539A. Two cases of grade 3 acute renal failure were attributed to DFRF4539A. There were no deaths; the MTD was not reached. DFRF4539A demonstrated limited activity in patients at the doses tested with 2 (5%) partial response, 1 (3%) minimal response, 18 (46%) stable disease, and 16 (41%) progressive disease. FcRH5 was confirmed to be expressed and occupied by antibody post-treatment and thus remains a valid myeloma target. Nevertheless, this MMAE-based antibody-drug-conjugate targeting FcRH5 was unsuccessful for myeloma.

Aim: This retrospective analysis evaluated chemotherapy-induced nausea and vomiting (CINV)-related hydration needs with palonosetron or granisetron extended-release subcutaneous (GERSC), approved in 2016 for CINV prevention. Materials & methods: At a community practice, CINV-related hydration per chemotherapy cycle was determined following highly (HEC) or moderately emetogenic chemotherapy (MEC) and a guideline-recommended antiemetic regimen: NK-1 receptor antagonist, dexamethasone and either palonosetron only, GERSC only, or palonosetron switched to GERSC. Results: Palonosetron-only patients (n = 93) had a significantly higher mean (standard deviation) hydration rate (0.9 [1.1]) than GERSC-only patients (n = 91; 0.3 [0.6]; p [Formula: see text]

BACKGROUND A phase 3 trial in patients with cancer who received chemotherapy has shown that subcutaneous (SC) APF530, a sustained-delivery formulation of granisetron, is noninferior to palonosetron in preventing acute (0-24 hours) and delayed (>24-120 hours) chemotherapy-induced nausea and vomiting (CINV). OBJECTIVES To investigate the sustainability of APF530 antiemetic responses during multiple chemotherapy cycles. METHODS 1,395 patients receiving moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) were randomized either to APF530 250 or 500 mg SC (containing granisetron 5 or 10 mg, respectively) or palonosetron 0.25 mg intravenously before cycle 1 of chemotherapy. Patients who received palonosetron in cycle 1 were rerandomized in cycles 2-4 to APF530 250 or 500 mg; those who received APF530 in cycle 1 continued their APF530 dose. Between-group response rates were compared using the Fisher exact test. RESULTS Complete response (CR; no emesis, no rescue medication) for APF530 500 mg with HEC increased from 81.3% to 87.8% over 4 cycles in the acute phase of CINV, and from 67.1% to 83.1% in the delayed phase. Rates were slightly lower with MEC. Within-cycle CR rates between APF530 doses showed no significant differences. With HEC, APF530 500 mg provided sustained CRs through 4 cycles of chemotherapy in 68.4% of patients in the acute phase and in 57.9% in the delayed phase; with MEC, corresponding CRs were 56.5% and 41.3%. Nausea prevention was nearly as effective as emesis prevention. LIMITATIONS Chemotherapy emetogenicity was classified according to Hesketh criteria during the time of this study. However, subsequent post hoc analyses indicate that reclassification according to newer ASCO emetogenicity guidelines did not alter the original study noninferiority conclusions. CONCLUSIONS CR rates with APF530 during the acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles.

Objectives The combination of pemetrexed and carboplatin is a standard first-line treatment for patients with advanced NSCLC. In this pilot phase II trial, we evaluated the feasibility of using pemetrexed and carboplatin as neoadjuvant therapy, prior to definitive surgical resection, for patients with localized NSCLC. Patients and methods Patients with potentially resectable, previously untreated, clinical stage IB-III, nonsquamous NSCLC were eligible for this trial. All patients received 4 cycles of pemetrexed (500 mg/m2) and carboplatin (AUC 6.0) administered at 21 day intervals. Three to 6 weeks after completion of chemotherapy, definitive surgical resection was attempted. The primary endpoint of this trial was the 3-year survival rate. Results Forty-six patients began protocol treatment, and 40 completed 4 courses of pemetrexed/carboplatin. Surgical resection was performed in 27 patients (59%); all had pathologic partial responses. The estimated 3-year survival rate for the entire group was 46%. Toxicity of neoadjuvant therapy was consistent with toxicity previously reported with pemetrexed/carboplatin. Conclusions Administration of 4 courses of pemetrexed/carboplatin was feasible. The efficacy was similar to neoadjuvant regimens previously investigated. A significant number of patients 19 of 46 (41%) in this trial did not have surgical resection after neoadjuvant therapy. Further investigation of the role of neoadjuvant pemetrexed/carboplatin requires a larger, randomized clinical trial.

BACKGROUND The prognosis of patients with higher risk myelodysplastic syndromes (MDS) remains poor despite available therapies. Histone deacetylase inhibitors have demonstrated activity in patients with MDS and in vitro synergy with azacitidine. METHODS A phase 2 randomized, placebo-controlled clinical trial of azacitidine and pracinostat was conducted in patients who had International Prognostic Scoring System intermediate-2–risk or high-risk MDS. The primary endpoint was the complete response (CR) rate by cycle 6 of therapy. RESULTS Of 102 randomized patients, there were 51 in the pracinostat group and 51 in the placebo group. The median age was 69 years. The CR rate by cycle 6 of therapy was 18% and 33% (P = .07) in the pracinostat and placebo groups, respectively. No significant differences in overall survival (median, 16 vs 19 months, respectively; hazard ratio, 1.21; 95% confidence interval, 0.66-2.23) or progression-free survival (11 vs 9 months, respectively; hazard ratio, 0.82; 95% confidence interval, 0.546-1.46) were observed between groups. Grade ≥3 adverse events occurred more frequently in the pracinostat group (98% vs 74%), leading to more treatment discontinuations (20% vs 10%). CONCLUSIONS The combination of azacitidine with pracinostat did not improve outcomes in patients with higher risk MDS. Higher rates of treatment discontinuation may partially explain these results, suggesting alternative dosing and schedules to improve tolerability may be required to determine the potential of the combination. Cancer 2017. © 2017 American Cancer Society.

Purpose Subcutaneous APF530 provides controlled sustained release of granisetron to prevent acute (0–24 h) and delayed (24–120 h) chemotherapy-induced nausea and vomiting (CINV). This randomized, double-blind phase 3 trial compared APF530 and palonosetron in preventing acute and delayed CINV after moderately (MEC) or highly emetogenic chemotherapy (HEC). Methods Patients receiving single-day MEC or HEC received single-dose APF530 250 or 500 mg subcutaneously (SC) (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg. Primary objectives were to establish APF530 noninferiority to palonosetron for preventing acute CINV following MEC or HEC and delayed CINV following MEC and to determine APF530 superiority to palonosetron for preventing delayed CINV following HEC. The primary efficacy end point was complete response (CR [using CI difference for APF530 − palonosetron]). A lower confidence bound greater than −15 % indicated noninferiority. Results In the modified intent-to-treat population (MEC = 634; HEC = 707), both APF530 doses were noninferior to palonosetron in preventing acute CINV after MEC (CRs 74.8 % [−9.8, 9.3] and 76.9 % [−7.5, 11.4], respectively, vs. 75.0 % palonosetron) and after HEC (CRs 77.7 % [−11.5, 5.5] and 81.3 % [-7.7, 8.7], respectively, vs. 80.7 % palonosetron). APF530 500 mg was noninferior to palonosetron in preventing delayed CINV after MEC (CR 58.5 % [−9.5, 12.1] vs. 57.2 % palonosetron) but not superior in preventing delayed CINV after HEC. Adverse events were generally mild and unrelated to treatment, the most common (excluding injection-site reactions) being constipation. Conclusions A single subcutaneous APF530 injection offers a convenient alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC.