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PURPOSE CheckMate 568 is an open-label phase II trial that evaluated the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line treatment of advanced/metastatic non–small-cell lung cancer (NSCLC). We assessed the association of efficacy with programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB). PATIENTS AND METHODS Two hundred eighty-eight patients with previously untreated, recurrent stage IIIB/IV NSCLC received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary end point was objective response rate (ORR) in patients with 1% or more and less than 1% tumor PD-L1 expression. Efficacy on the basis of TMB (FoundationOne CDx assay) was a secondary end point. RESULTS Of treated patients with tumor available for testing, 252 patients (88%) of 288 were evaluable for PD-L1 expression and 98 patients (82%) of 120 for TMB. ORR was 30% overall and 41% and 15% in patients with 1% or greater and less than 1% tumor PD-L1 expression, respectively. ORR increased with higher TMB, plateauing at 10 or more mutations/megabase (mut/Mb). Regardless of PD-L1 expression, ORRs were higher in patients with TMB of 10 or more mut/Mb (n = 48: PD-L1, ≥ 1%, 48%; PD-L1, < 1%, 47%) versus TMB of fewer than 10 mut/Mb (n = 50: PD-L1, ≥ 1%, 18%; PD-L1, < 1%, 5%), and progression-free survival was longer in patients with TMB of 10 or more mut/Mb versus TMB of fewer than 10 mut/Mb (median, 7.1 v 2.6 months). Grade 3 to 4 treatment-related adverse events occurred in 29% of patients. CONCLUSION Nivolumab plus low-dose ipilimumab was effective and tolerable as a first-line treatment of advanced/metastatic NSCLC. TMB of 10 or more mut/Mb was associated with improved response and prolonged progression-free survival in both tumor PD-L1 expression 1% or greater and less than 1% subgroups and was thus identified as a potentially relevant cutoff in the assessment of TMB as a biomarker for first-line nivolumab plus ipilimumab. more...

Purpose Concurrent chemoradiotherapy is standard treatment for patients with stage III non–small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute–supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non–small-cell lung cancer from 1990 to 2012. Overall survival (OS), progression-free survival, and AEs were compared between patients age ≥ 70 (elderly) and those younger than 70 years (younger). Unadjusted and adjusted hazard ratios (HRs) for survival time and CIs were estimated by single-predictor and multivariable frailty Cox models. Unadjusted and adjusted odds ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable generalized linear mixed-effect models. Results A total of 2,768 patients were classified as younger and 832 as elderly. In unadjusted and multivariable models, elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95% CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly and younger patients had similar progression-free survival (HR, 1.01; 95% CI, 0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients had a higher rate of grade ≥ 3 AEs in unadjusted and multivariable models (OR, 1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively). Grade 5 AEs were significantly higher in elderly compared with younger patients (9% v 4%; P < .01). Fewer elderly compared with younger patients completed treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs (20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had a higher rate of death during treatment than younger patients. more...

9560 Background: In Part 1 of the phase II CheckMate 568 study (NCT02659059), NIVO + IPI was active and tolerable in patients (pts) with advanced NSCLC. The addition of chemo to dual immune checkpoint inhibitor therapy may further improve initial disease control. We report results from Part 2 of CheckMate 568, which evaluates NIVO + IPI combined with 2 cycles of chemo in pts with advanced treatment-naive NSCLC. Methods: Adult pts with untreated stage IV NSCLC received NIVO 360 mg Q3W + IPI 1 mg/kg Q6W combined with 2 cycles of histology-based platinum-doublet chemo, followed by NIVO + IPI without chemo until disease progression/unacceptable toxicity for ≤ 2 years. The primary endpoints were dose-limiting toxicity (DLT) within the first 9 weeks and safety/tolerability. Treatment was considered safe if ≤ 25% of at least 22 evaluable pts had a DLT. DLTs included but were not limited to: uncontrolled grade 3 non-skin treatment-related adverse events (TRAEs), grade 4 TRAEs, grade 2 treatment-related pneumonitis not resolved within 14 days, and treatment-related hepatic function abnormalities. Results: In total, 36 pts received treatment; 97% of pts completed 2 cycles of chemo combined with NIVO + IPI. Three pts discontinued IPI while continuing NIVO. Minimum follow-up was 14.9 months. Only 1 (3%) pt experienced a DLT (transient, asymptomatic grade 3 AST and ALT elevation) within the first 9 weeks. The elevation occurred on cycle 1, day 21 and resolved 2 weeks later with discontinuation of IPI, delay of NIVO, and treatment with prednisone; chemo was continued throughout and NIVO was restarted thereafter without recurrent toxicity. Grade 3–4 TRAEs occurred in 21 (58%) pts. Eight (22%) pts experienced a TRAE leading to discontinuation, most commonly colitis, encephalopathy, pneumonitis, and arthralgia (each in 2 [6%] pts); these events occurred outside of the 9-week window for DLT assessment. The most common select TRAEs (defined as AEs of potential immunologic causes) were skin related (18 [50%] pts); the most common grade 3–4 select TRAEs were endocrine (3 [8%] pts), skin related, gastrointestinal, and pulmonary (each in 2 [6%] pts). No treatment-related deaths occurred. Updated safety in addition to efficacy data will be presented. Conclusions: In pts with untreated advanced NSCLC, the addition of 2 cycles of platinum-doublet chemo to NIVO + tumor-optimized IPI was tolerable. No unexpected safety signals were observed. Clinical trial information: NCT02659059 . more...

e24110 Background: Palliative care (PC) improves symptom burden, patient and family distress and quality of life of patients with advanced illnesses. Previous evidence has shown that non-physician providers (NPP) can be effective in delivering care with minimal physician support. NPP-led PC interventions could potentially address gaps in the workforce and provide access to PC services. The overall objective of this systematic review is to evaluate the effectiveness of NPP-led PC interventions in the management of adults with cancer. Methods: We searched ten electronic databases up to October 2018 for randomized or cluster control trials that evaluated NPP-led interventions in both adults receiving end of life care for advanced malignancies and/or their caregivers. NPPs included nurses, advanced practitioners, social workers or case-worker. Interventions included symptom management, hospice care, advance care planning (ACP) or decision support. We recorded the following outcomes: quality of life, patient symptoms (anxiety, depression, pain or distress), satisfaction with care and ACP. Study quality was assessed using the Cochrane risk of bias tool version 2.0. Results: Overall 5,241 publications were screened, resulting in 207 publications that underwent full text review. 13 studies (n = 2,007 participants) included only patients with diagnoses of cancer and an additional 2 studies (n = 396 participants) focused on mixed diagnoses of advanced illness, including cancer. Only 2 studies focused on both caregivers and patients. A nurse was the lead provider in 13 studies, and an advance practitioner in 2 studies. The NPP-led interventions were mostly psychosocial with four also providing symptom management. Interventions mostly consisted of education, care coordination information and support. A total of 3 studies focused solely on ACP, while 2 additional studies addressed this as part of the planned intervention. Nine studies reported quality of life outcomes and seven studies reported on anxiety and depression. There was considerable heterogeneity among the studies with respect to the nature of the intervention and the diagnoses of the study participants. All but one of the studies examined had high risk of bias, mostly due to issues related to missing outcome data or measurement of the outcome. Conclusions: In the setting of changing models of population health care delivery, the results of this systematic review could provide evidence for implementation of non-physician-led palliative care services outside of clinical trials. more...

e21683 Background: Combination chemo-immunotherapy is a well-established frontline therapeutic option for treatment naïve NSCLC. Dual immune checkpoint blockade (ICB) with nivolumab (nivo) and ipilimumab (ipi) has demonstrated improved clinical outcomes compared with chemotherapy alone in this setting. Combination dual ICB with low-dose chemotherapy may have advantages of preventing early disease progression and potentiating immunogenic response to treatment. Methods: We are conducting a single arm phase II clinical trial of nivo 360 mg IV Q3 weeks, ipi 1 mg/kg IV Q6 weeks, and weekly paclitaxel 80 mg/m2 IV on d1 and d8 of a 21 day cycle in ECOG 0-1 patients (pts) with treatment naïve NSCLC. Paclitaxel is stopped after a total of 4-6 cycles. The primary endpoint of the trial is progression free survival (PFS) with secondary endpoints of safety and objective response rate (ORR) by independent radiologic review. Interim results are presented from the first 23 evaluable pts, of a planned sample size of 49. Results: 23 pts were enrolled and evaluable with a mean age 63.8 years, 56.5% ECOG 0, 87% current/previous smoking history, and 70% adenocarcinoma. PDL1 score for < 1%, 1-49%, ³ 50% was seen in 9 (39.1%), 4 (17.4%), and 10 (43.5%) pts, respectively. Median time of follow up was 6.5 months (range 1.4–15.0). Partial response was observed in 14 pts, stable disease was seen in 8 pts, and 1 pt progressed during cycle 1, resulting in an ORR of 61%. Grade 3 or higher toxicity at least possibly attributed to study treatment was seen in 47.8% of 23 AE evaluable patients, of which included 4 cases of secondary adrenal insufficiency. Other toxicity rates were as expected for the respective agents. Conclusions: This is the first trial to evaluate weekly paclitaxel with nivo plus ipi in pts with untreated NSCLC. This regimen has demonstrated highly encouraging clinical activity with a manageable toxicity profile. The study is ongoing and updated results will be presented at the annual meeting. Clinical trial information: NCT03573947. more...

11028 Background: Previous research has indicated challenges integrating new immuno-oncology agents (IOAs) and predictive immune biomarkers into practice. Barriers, clinical gaps and underlying causalities explaining these challenges, however, are poorly understood. Methods: A mixed-methods educational needs assessment was conducted with physicians from 6 specialties (oncology, interventional radiology, pathology, pulmonology, emergency medicine and rheumatology), clinical pharmacists, physician assistants and advanced nurse practitioners involved in the care of cancer patients in the United States. Semi-structured interviews and discussion groups were thematically analyzed to identify challenges, barriers and underlying causalities. Qualitative findings subsequently informed the development of online surveys, which served to quantify findings. The following findings pertain to oncologists. Results: A total of 660 health care providers participated in the study, in which 17 interviews and 88 surveys were completed with oncologists. Seventy-two percent reported sub-optimal knowledge of the interactions between IOAs and the tumor’s micro-environment, while 62% reported sub-optimal skills determining which IOA to select based on this information. Oncologists reported sub-optimal knowledge of best practices for using IOAs to treat cancer in presence of an autoimmune disease (74%-80% depending on condition), and sub-optimal skills weighing the risks and benefits of prescribing IOAs for these profiles (66%-77%). In addition, 50% of oncologists reported feeling overwhelmed by the volume of new IOAs being made available. Many oncologists expressed doubts regarding the clinical benefit (59%) and innovative nature (43%) of emerging IOAs. Finally, 46% reported limited skills identifying viable treatment options based on pharmacodiagnostic test reports. Barriers to having predictive biomarkers inform treatment decisions included sub-optimal communication between specialists regarding specimen requirements and desired biomarker information. Conclusions: This study demonstrates the need to further support healthcare professionals as they face challenges integrating new IOAs and predictive immune biomarkers into practice. Given the wide array of IOAs becoming available each year, addressing the knowledge, skills, confidence and attitude gaps identified in this study could help improve health care delivery and potentially optimize outcomes for cancer patients. more...

e18193 Background: Steroids and Intravenous immunoglobulin (IVIG) are considered as the first line of therapy in immune thrombocytopenia (ITP) when treatment is indicated. Approximately 5% of patients with untreated CLL and 25-30% of patients with previously treated CLL have thrombocytopenia. There is limited data about ITP treatment patterns and therapeutic responses in patients with CLL. Methods: This is a retrospective cohort study using the 2016 National Inpatient Sample of adults ( > 18 years) hospitalized for ITP as the admitting diagnosis and CLL as a secondary diagnosis based on ICD-10 codes. Primary outcomes were rate of administration of IVIG, splenectomy, platelet transfusion and packed red blood cell transfusion during same admission. Length of hospitalization was a secondary outcome. Multivariate linear regression was used to adjust for cofounders of age, gender, race and Charlson comorbidity Index. STATA 15 was used for analysis. Results: 14,490 patients were admitted for ITP (56% females, mean age 46), of which 255 had CLL (95 females, mean age was 72.4). On multivariate linear regression there was a significant increase in the use of IVIG among ITP patients with CLL (OR: 2.11; 95%-CI 1.05-4.23, P = 0.03). While there was no difference in terms of splenectomy rate ( OR: 0.35, 95% CI 0.05 to 2.52, p = 0.28 ) or rate of platelet transfusion (Odds ratio 1.15, 95% CI 0.63 to 2.08, p = 0.65) and packed red blood cell transfusion (Odds ratio 1.03, 95% CI 0.44 to 2.39, p = 0.94) between patients who have ITP with CLL and patients admitted with ITP without CLL. No statistical difference was found in hospitalization length. Conclusions: Patients hospitalized for ITP with CLL were more likely to require IVIGs. This could be explained by several theories including the need for a more rapid increase in platelet count as thrombocytopenia may be more severe due to bone marrow infiltration by CLL, immune dysfunction and/or treatment induced thrombocytopenia. Additionally, CLL patients can have hypogammaglobinemia making them more likely to get IVIG as a treatment of choice for ITP and as an immune replacement. Also ITP patients with CLL may have less response to steroids, as was noted in a previous study. Fear of atypical infections due to steroids in CLL patients may result in increased IVIG use. Further research of the microenvironment of ITP in CLL patients might explain the difference in treatment pattern and therapeutic response in this population. more...

8516 Background: Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting DLL3, a Notch ligand expressed in SCLC but not normal tissue. Nivo ± Ipi has activity in 2L+ SCLC. Preliminary data suggest Rova-T may result in immunogenic cell death, complementing effects of Nivo ± Ipi. Methods: Eligibility: DLL3 expression (DLT phase only), progression after ≥1 line of therapy including a platinum-based regimen; ECOG 0-1; no prior immunotherapy. All pts received 0.3 mg/kg Rova-T IV on Day 1 of two 6-wk cycles. Cohort 1 (C1) also received two 3-wk cycles of 360 mg Nivo beginning on wk 4. Cohort 2 (C2) received four 3-wk cycles of 1 mg/kg Nivo and 1 mg/kg Ipi beginning on wk 4. Both cohorts then received 480 mg Nivo q4wks until PD. Primary objective: safety. Secondary: antitumor activity by RECISTv1.1, OS. Exploratory: PK. Results: As of Sep 7, 2018, 30 pts were dosed in C1 and 12 in C2. 55% were DLL3 high (≥75% DLL3 expression). 28 (67%) completed 2 planned cycles of Rova-T. 4 pts (1 in C1, 3 in C2) experienced DLTs including rash (3), pneumonitis (1) and colitis (1). C1 completed recruitment, and C2 enrollment was stopped after DLT evaluation phase. Preliminary PK showed Nivo±Ipi had no substantial effect on Rova-T exposure. Clinical trial information: NCT03026166. Conclusions: Despite activity in 2L+ ED-SCLC, Rova-T with Nivo/Ipi is not appropriate due to DLTs. Rova-T/Nivo demonstrated some durable responses; however, the safety data suggest that optimization of dose and schedule is warranted. NCT03026166.[Table: see text] more...

8507Background: Small cell lung cancer (SCLC) accounts for ~15% of lung cancer with no approved therapies in ≥ 3rd line (3L) patients (pts). In 3L pts, historical data demonstrate a median overall survival (mOS) of 4.7 mo and a best overall response of 18%; no historical data exist for objective response rate (ORR). Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting Delta-like 3 protein (DLL3), an atypical Notch ligand that is highly expressed in SCLC but not normal tissue. A Ph1 study showed that Rova-T has antitumor activity in pts with recurrent SCLC and high DLL3 expression, and a manageable safety profile. Methods: TRINITY was an open-label, single-arm, Ph2 study of Rova-T in adult pts with DLL3-expressing SCLC (NCT02674568). Eligibility: ≥ 2 prior systemic regimens including ≥ 1 platinum-based regimen; ECOG 0-1; stable CNS disease. Pts received 0.3 mg/kg Rova-T intravenously on Day 1 of a 6-week cycle for 2 cycles. DLL3-high (hi) pts had ≥ 75% tumor cells positive by immunohis... more...

e21222Background: Data describing therapeutic outcomes in patients with non-small-cell lung cancers (NSCLC) harboring BRAF alterations remains limited. Methods: A retrospective cohort study was con... more...

9092 Background: Platinum-based chemo is a standard first-line (1L) therapy for NSCLC lacking actionable gene alterations. Preclinical evidence suggests that chemo can play an immunomodulatory role and induce tumor antigen release, supporting combining chemo with immunotherapy. Atezo is a humanized and Fc-region-modified monoclonal anti-programmed death-ligand-1 (PD-L1) antibody that blocks interaction with PD1 or B7.1. The GP28328 study (NCT01633970) assessed safety and efficacy of atezo plus 1L chemo regimens in multiple tumor types. Methods: In this multicenter, multi-arm study, patients (pts) with locally advanced or metastatic NSCLC with no prior chemo for advanced disease received 15 mg/kg atezo IV q3w with standard doses of chemo (Arm C: carboplatin [carbo]+paclitaxel q3w; Arm D: carbo+pemetrexed q3w; Arm E: carbo+nab-paclitaxel qw) all for ≤6 cycles followed by atezo maintenance until loss of clinical benefit (+ pemetrexed maintenance until progression, Arm D). The primary endpoint was safety; secondary endpoints were overall response rate (ORR), PFS, and OS. Results: By the 30 Aug 2016 cut-off, 76 NSCLC pts were evaluable (n = 25, 25, 26 for Arms C, D, E, respectively). At this cut-off, the most common treatment-related grade 3–4 adverse events (AEs) were neutropenia (36% C, 36% D, 42% E) and anemia (16% C, 16% D, 31% E). Three potentially related grade 5 AEs were seen (arm C: pneumonia; arm D: systemic candida; arm E: autoimmune hepatitis). Confirmed ORRs were 36%, 64%, 46% for Arms C, D (1 CR), and E (4 CR). Median PFS (95% CI) was 7.1 months (4.2–8.3) for C, 8.4 months (4.7–11) for D, and 5.7 months (4.4–14.8) for E. Median OS (95% CI) was 12.9 months (8.8–not evaluable) for C, 19.3 months (14.7–27.4) for D, and 14.8 months (12.7–not evaluable) for E. Conclusions: Atezo was well tolerated when combined with various chemo regimens for advanced NSCLC. Clinical activity in terms of ORR was favorable supporting potential synergy between atezo and chemo. PFS and OS data show promising benefits, but are limited by small numbers and wide confidence intervals. Phase III studies that include chemotherapy and atezolizumab are currently ongoing. Clinical trial information: NCT01633970. more...

9093 Background: The fully human anti–PD-1 antibody N offers long-term OS benefit in patients (pts) with previously treated adv NSCLC. Adding I (anti–CTLA-4 antibody) to N has been shown to improve clinical activity vs either agent alone in multiple tumor types. We present long-term data for 1L N+I treatment of pts with adv NSCLC from CheckMate 012. Methods: In two cohorts in this phase 1 study, pts with recurrent stage IIIb/IV, chemotherapy-naive NSCLC and ECOG PS 0–1 received N 3 mg/kg Q2W combined with I 1 mg/kg Q12W (n=38) or Q6W (n=39) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was safety and tolerability. Secondary endpoints included investigator-assessed ORR (RECIST v1.1) and PFS. Exploratory endpoints included OS and efficacy by tumor PD-L1 expression. Results: In the N+I Q12W and N+I Q6W cohorts, respectively, 42% and 31% of pts experienced grade 3–4 treatment-related (TR) AEs; 18% in each cohort discontinued due to any-grade TRAEs. The most frequently reported any-grade TRAEs were pruritus (26%) and diarrhea (21%) with N+I Q12W, and fatigue (26%) and diarrhea (23%) with N+I Q6W. There were no TR deaths. N+I showed promising efficacy (table). While efficacy was enhanced with increasing PD-L1 expression, activity was noted in pts with more...

8503 Background: Patients (pts) with advanced SCLC after first-line platinum-based chemotherapy (PLT-CT) have a poor prognosis and limited treatment options. CheckMate 032 is a phase I/II trial evaluating multiple regimens of nivo ± ipi in solid tumors, including advanced SCLC. Tolerability and efficacy of nivo ± ipi were demonstrated in early results from the initial treatment arms (Antonia, Lancet Oncol 2016), prompting long-term follow-up and the addition of a randomized expansion cohort to further evaluate nivo ± ipi in advanced SCLC. Methods: In the initial treatment arms, pts with advanced SCLC and disease progression after prior PLT-CT were assigned to nivo (3 mg/kg Q2W; n = 98) or nivo 1 + ipi 3 (1 mg/kg and 3 mg/kg Q3W x 4, then nivo 3 Q2W; n = 61); safety/efficacy was assessed with a follow-up of ~18 mo. In the subsequent SCLC expansion cohort, pts were randomized 3:2 to nivo vs nivo 1 + ipi 3 and stratified by number of prior therapies. The primary endpoint was objective response rate (ORR). Results: Updated efficacy/safety results from the initial (non-randomized) nivo and nivo 1 + ipi 3 arms are summarized in the table. Responses were durable and occurred regardless of PD-L1 expression or PLT-sensitivity; safety was consistent with prior nivo ± ipi studies. In the expansion cohort, 247 pts were randomized to nivo or nivo 1 + ipi 3. The presentation will contain the first report of efficacy/safety results and subgroup analyses from this randomized expansion cohort. Conclusions: Durable responses are observed with nivo and nivo + ipi in pts with previously treated SCLC. The expansion cohort represents the first randomized evaluation of combined immune checkpoint blockade in SCLC. Clinical trial information: NCT01928394. [Table: see text] more...

26 Background: Ipilimumab (Ipi) is a humanized CTLA-4 antibody that blocks binding of CTLA-4 to B7, permitting T cell activation through CD28. Phased in Ipi added to chemotherapy (C) may enhance efficacy in NSCLC. Methods: Patients with stage 2 or 3A NSCLC received neoadjuvant carboplatin AUC6 plus paclitaxel 200 mg/m2 every 21 days for 3 cycles and Ipi (10 mg/kg) was given on day 1 for cycles 2 and 3. Blood for immune profiling of circulating T cells was collected at baseline, after chemotherapy alone, and after chemotherapy plus Ipi. Tumor infiltrating lymphocytes (TIL) were derived from 7 available tumors. Polychromatic flow cytometry (PFC) analyses were performed on peripheral blood mononuclear cells (PBMC) and TIL. Objective response rates were assessed according to RECIST 1.1 criteria. Results: Of the 24 patients enrolled on this study, objective responses after 3 cycles of neoadjuvant C plus ipi included 2 PD, 8 SD, and 14 PR. Phenotypic analyses revealed that PBMC from all 24 patients were highly activated following two cycles of Ipi (cycle 3) as evidenced by significantly increased frequencies of CD28, ICOS, HLA-DR, PD-1, and CTLA-4 expressing CD4+ cells; and ICOS, HLA-DR, and CTLA-4 expressing CD8+ cells. The frequencies of Tregs were highly variable among the 24 participants. Two of the 24 participants had levels of MDSC cells above 15%. TIL contained far greater frequencies of activated CD4+ and CD8+ cells than found in the PBMC at cycle 3. Tumor associated antigen (TAA)-specific CD4+ or CD8+ cells were detected at baseline in 4 patients (24%), but their relative frequencies remained unaltered by Ipi therapy. No patients developed detectable de novo TAA reactivities while on Ipi therapy. Conclusions: Combined neoadjuvant Ipi plus chemotherapy produced significantly increased frequencies of highly activated CD4+ and CD8+ populations in the peripheral blood and the tumor microenvironment. TAA-specific CD4+ or CD8+ cells were detected in PBMC at baseline in a subset of patients. No TAA-reactive T cells were detected among the 7 TIL samples analyzed. Analysis for predictive or pharmacodynamic biomarkers is ongoing. Clinical trial information: NCT01820754. more...

9025Background: Nivo, afully human IgG4 programmed death-1 immune checkpoint inhibitor, is approved in the US for pts with previously treated metastatic NSCLC and in the EU for pretreated locally a... more...

Poster Discussion Session: Lung Cancer-Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers: abstract 8508

LBA8505 Background: SCLC remains among the most deadly of malignancies. Rovalpituzumab tesirine is a first-in-class ADC comprised of a humanized monoclonal antibody against DLL3, a dipeptide linker, and a pyrrolobenzodiazepine (PBD) dimer toxin. DLL3 is highly expressed in neuroendocrine tumors, including approximately 80% of SCLC. The emerging results of the SCLC patients (pts) in a first-in-human study (NCT01901653) are reported here. Methods: Pts with progressive SCLC after at least 1 previous systemic therapy were eligible. Efficacy was assessed by the investigator via RECIST v1.1, and toxicity graded per CTCAE v4.03. When available, archived tumor tissue was assessed retrospectively for DLL3 expression by immunohistochemistry. Results: Seventy-four (74) pts were enrolled at dose levels ranging from 0.05 to 0.8 mg/kg at either q3w or q6w. Among evaluable pts treated at doses of 0.2-0.4 mg/kg, 15/61 (25%; 95% CI 15-37%) achieved a best response of PR or CR, and 44/61 (72%; 95% CI 59-83%) achieved clinical benefit (best response of at least SD). Among pts with available archive tissue specimens and ≥ 50% of cells expressing DLL3 (DLL3hi, an intended companion diagnostic cutoff), 12/22 (55%; 95% CI 32-76%) achieved a best response of PR or CR, and 20/22 (91%; 95% CI 71-99%) achieved clinical benefit, with a median overall survival of 8 (range 1-18+) months. In 3rd line DLL3hi pts (n = 10), where no approved therapy currently exists, the ORR and CBR were 70% and 90%, respectively, with at least 4 evaluable pts achieving OS of > 6 (8, 15, 18 and 18) months. Among responders treated at the phase 2 dose of 0.3 mg/kg, the median duration of response was 6 (range 1-8+) months. Among all SCLC pts, the most common grade 3+ toxicities considered study drug-related have included serosal effusions (14%), thrombocytopenia (12%) and skin reactions (8%). Conclusions: With manageable toxicity, rovalpituzumab tesirine demonstrates encouraging single-agent anti-tumor activity and durability in recurrent or refractory SCLC. A single-arm pivotal study in 3rd line DLL3-expressing SCLC has been initiated. Clinical trial information: NCT01901653. more...

TPS8579Background: Most SCLC pts present with ED-SCLC. Initial response rates are high, but disease often rapidly recurs or progresses. Outcomes with second-line treatment are poor. No maintenance therapy has been approved for pts who respond to first-line PT-DC. Nivo, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor, is approved for previously treated metastatic NSCLC in the US and for previously treated squamous NSCLC in the EU based on 2 phase III trials demonstrating superior survival over docetaxel. Nivo monotherapy and nivo + ipi, a fully human IgG1 cytotoxic T lymphocyte antigen-4 immune checkpoint inhibitor, are being evaluated in previously treated pts with advanced or metastatic SCLC in a phase I/II trial (CheckMate 032, SCLC cohort). Nivo (vs chemotherapy) is also being evaluated in relapsed SCLC in a phase III trial (CheckMate 331). From CheckMate 032, preliminary data of nivo and nivo + ipi has shown antitumor activity with durable tumor responses and manageable safety... more...

3001Background: Nivo + ipi is approved in adv melanoma and has demonstrated clinical activity and manageable safety in various solid tumors. CheckMate 012 is a phase I study of nivo monotherapy or ... more...

LBA109 Background: Options for advanced non-SQ NSCLC patients (pts) who progress after platinum-based doublet chemotherapy (PT-DC) are limited, with minimal improvement in overall survival (OS). We report results from a randomized, global phase III study of NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC and tyrosine kinase inhibitor, if eligible. Methods: Pts were randomized to NIVO 3 mg/kg Q2W (n=292) or DOC 75 mg/m2 Q3W (n=290) until progression or discontinuation due to toxicity/other reasons. Primary objective was OS; Secondary objectives were investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression, quality of life, and safety. Results: NIVO demonstrated superior OS (HR=0.73; 96% CI: 0.59, 0.89; P=0.00155) and improved ORR (19.2% vs 12.4%; P=0.0235). HR for PFS was 0.92 (95% CI: 0.77, 1.11; P=0.393). PD-L1 expression was associated with benefit from NIVO (Table). In PD-L1+ pts, NIVO showed improved efficacy across all endpoints at predefined 1%, 5%, and 10% cut- points. Grade 3–5 drug-related AEs occurred in 10.5% (30/287) of NIVO and 53.7% (144/268) of DOC pts. No deaths were related to NIVO vs 1 DOC-related death. After discontinuation, 42.1% of NIVO and 49.7% of DOC pts received subsequent systemic therapy. Conclusions: NIVO demonstrated superior OS vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC. The safety profile of NIVO 3 mg/kg Q2W was favorable vs DOC. NIVO demonstrated survival benefit across histologies in two randomized phase III trials. Clinical trial information: NCT01673867. [Table: see text] more...