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The National Center for Advancing Translational Science (NCATS) seeks to improve upon the translational process to advance research and treatment across all diseases and conditions and bring these interventions to all who need them. Addressing the racial/ethnic health disparities and health inequities that persist in screening, diagnosis, treatment, and health outcomes (e.g., morbidity, mortality) is central to NCATS’ mission to deliver more interventions to all people more quickly. Working toward this goal will require enhancing diversity, equity, inclusion, and accessibility (DEIA) in the translational workforce and in research conducted across the translational continuum, to support health equity. This paper discusses how aspects of DEIA are integral to the mission of translational science (TS). It describes recent NIH and NCATS efforts to advance DEIA in the TS workforce and in the research we support. Additionally, NCATS is developing approaches to apply a lens of DEIA in its activities and research – with relevance to the activities of the TS community – and will elucidate these approaches through related examples of NCATS-led, partnered, and supported activities, working toward the Center’s goal of bringing more treatments to all people more quickly.

This chapter grapples with the question: How do Buddhist Vietnamese American home altar practices organize domestic life? In the following analysis, domestic altars materialize as shifting positions in the realms of the diasporic, the political, and the civic. First, the author argues that Vietnamese American home altar practices are organic, material spaces that practitioners manipulate to invoke the intersections between the homeland and a new home. Second, domestic altars enact an individualized moral or spiritual orientation and also express a complex and politically engaged imaginary through the particular positioning of objects and imagery. And third, they can reveal a creative, adaptable, and civically engaged Vietnamese American spirituality and subjectivity. In sum, home altar practices organize and manifest religious embodiment, political and civic proclivities, and an appeal to diasporic and national belonging.

Background aims Autologous cell therapy (AuCT) is an emerging therapeutic treatment that is undergoing transformation from laboratory- to industry-scale manufacturing with recent regulatory approvals. Various challenges facing the complex AuCT manufacturing and supply chain process hinder the scale out and broader application of this highly potent treatment. Methods We present a multiscale logistics simulation framework, AuCT-Sim, that integrates novel supply chain system modeling algorithms, methods, and tools. AuCT-Sim includes a single facility model and a system-wide network model. Unique challenges of the AuCT industry are analyzed and addressed in AuCT-Sim. Decision-supporting tools can be developed based on this framework to explore “what-if” manufacturing and supply chain scenarios of importance to various cell therapy stakeholder groups. Results Two case studies demonstrate the decision-supporting capability of AuCT-Sim where one investigates the optimal reagent base stocking level, and the other one simulates a reagent supply disruption event. These case studies serve as guidelines for designing computational experiments with AuCT-Sim to solve specific problems in AuCT manufacturing and supply chain. Discussion This simulation framework will be useful in understanding the impact of possible manufacturing and supply chain strategies, policies, regulations, and standards informing strategies to increase patient access to AuCT.

This phase 1-2 study evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2 to 4. In part 3, both study drugs were dosed, same day, for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (ORR; N = 91) was 85%, with 67% achieving a complete response (CR). At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI], 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow-up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns. This trial was registered at www.clinicaltrials.gov as #NCT02572167.

Background Brentuximab vedotin (BV) is an antibody-drug conjugate (ADC) composed of a CD30-directed monoclonal antibody, a protease-cleavable linker, and the microtubule-disrupting agent, monomethyl auristatin E (MMAE). Direct cytotoxicity, driven by MMAE, is at the heart of the multifaceted anticancer activity of BV (Sutherland 2006). BV was the first ADC to be approved in multiple cancer types, including treatment-naïve Stage III or IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) (Connors 2017). Nivolumab is a fully humanized monoclonal antibody that targets programmed cell death protein 1 and is approved for the treatment of adults with relapsed/refractory (R/R) cHL. Both agents have been well tolerated with encouraging activity when combined with multi-agent chemotherapy. BV plus nivolumab was evaluated as a frontline treatment option for patients with cHL who are ≥60 years of age and ineligible for, or declined, conventional combination chemotherapy. The ongoing study reported an objective response rate (ORR) of 82% in 11 evaluable patients, and BV appears to be well tolerated in this population (Friedberg 2018). The combination of BV and nivolumab produced a 67% complete response (CR) rate and an estimated 3-year progression-free survival (PFS) rate of 77% in 93 patients with R/R cHL treated in the first-line salvage setting (Advani 2021). BV plus doxorubicin and dacarbazine (AD) without radiation therapy was evaluated in 34 patients with non-bulky Stage I or II cHL. BV-AD treatment resulted in interim and end of treatment (EOT) CR rates of 94% and 97%, respectively. The 4-year PFS and overall survival (OS) estimates were 91% and 100%, respectively. Peripheral sensory neuropathy (PSN) was low grade and only 1 patient had persistent PSN at the last follow-up (Abramson 2021). Part C of this study will evaluate BV, nivolumab, doxorubicin, and dacarbazine (AN+AD) in patients with Stage I or II cHL without bulky disease, a patient population similar to that studied in Abramson 2021. Based on the results of the trials summarized above, it is reasonable to expect that the combination of AN+AD will result in high response rates and be well tolerated, with potentially less toxicity compared with A+AVD. Study Design and Methods SGN35-027 (NCT03646123) is an open-label, multiple part, multicenter, phase 2 clinical trial of BV in patients with Stage III or IV cHL evaluating the efficacy and safety of A+AVD when administered with growth factor prophylaxis (Part A). Part B will evaluate the combination of AN+AD in patients with Stage I or II cHL with bulky mediastinal disease or Stage III or IV cHL. Part C will evaluate the efficacy and tolerability of AN+AD in patients with Stage I or II cHL without bulky disease. The primary objective of Parts B and C is to estimate the CR rate at EOT in patients with treatment-naïve cHL. Approximately 240 patients will be enrolled in this study: 40 in Part A, 50 in Part B, and 150 in Part C. Parts A and B have completed enrollment. Patients in Part C must have histologically confirmed cHL and have an ECOG performance status of ≤2. Patients with nodular lymphocyte-predominant HL or prior treatment with immune checkpoint inhibitors will be ineligible for enrollment. Patients in Part C will be treated with BV 1.2 mg/kg, nivolumab 240 mg, doxorubicin 25 mg/m 2, and dacarbazine 375 mg/m 2, administered separately by intravenous infusion on Days 1 and 15 of each 28-day cycle. Patients in Part C will receive 4 cycles of treatment. The primary efficacy endpoint is the CR rate at EOT with AN+AD in patients with previously untreated cHL. Duration of response, duration of complete response, event-free survival, PFS, ORR, and safety and tolerability of AN+AD will be evaluated as secondary endpoints. Efficacy will be assessed by PET/CT scans at Cycle 2 and EOT; disease response and progression for Part C will be assessed using the LYRIC modification of the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014). Patients will be followed for disease progression and OS for 5 years. Safety and efficacy endpoints will be summarized with descriptive statistics. The CR rate at EOT and its two-sided 95% confidence interval will be presented (Clopper 1934). Time-to-event endpoints will be analyzed using Kaplan-Meier methodology. Enrollment for Part C is ongoing in the US, with plans for global expansion. Disclosures Flinn: MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Friedman: Seagen Inc.: Research Funding. Ho: Seagen Inc.: Current Employment, Current equity holder in publicly-traded company.

Introduction Brentuximab vedotin (BV) and nivolumab are both active and well tolerated in patients (pts) with classical Hodgkin lymphoma (cHL) and were previously studied in first salvage (overall response rate [ORR] 85%; complete response [CR] 67%) (Advani 2021) and as firstline therapy in older adults (ORR 95%; CR 79%) (Yasenchak 2019). BV is approved for the treatment of adults with treatment-naïve Stage III or IV cHL in combination with doxorubicin, vinblastine, and dacarbazine (AVD) (Connors 2017) and targets CD30, a receptor expressed on the Reed-Sternberg cells. Nivolumab is approved for treatment of adults with relapsed/refractory cHL and restores antitumor immunity by blocking the PD-1 receptor on activated T-cells. The combination of BV plus nivolumab demonstrated promising activity that supports this combination when evaluated as a frontline treatment option for pts over 60 years of age with cHL (Friedberg 2018). Additionally, in pts with non-bulky Stage I or II cHL, treatment with BV plus doxorubicin and dacarbazine (AD) resulted in a CR rate of 97% at end of treatment (EOT), as well as a promising 4-year progression-free survival (PFS) estimate of 91%. Importantly, there were no cases of ≥Grade 3 peripheral neuropathy and only 9% were Grade 2 (Abramson 2021). Herein, we present preliminary safety results from Part B of this phase 2 study, where combination treatment with AN+AD (BV, nivolumab, doxorubicin, and dacarbazine) was well tolerated without excessive dose modifications or discontinuations and is consistent with the known safety profiles of the individual components of this treatment regimen. Methods SGN35-027 (NCT03646123) is an open-label, multiple part, multicenter, phase 2 clinical trial. Part B of this study enrolled pts with Ann Arbor Stage I or II cHL with bulky mediastinal disease (defined as ≥ 10 cm) or Stage III or IV cHL. Pts received up to 6 cycles of AN+AD (consisting of BV 1.2 mg/kg, nivolumab 240 mg, doxorubicin 25 mg/m 2, and dacarbazine 375 mg/m 2). All study drugs were administered by IV infusion on Days 1 and 15 of each 28-day cycle. The primary endpoint was CR rate at EOT. Secondary endpoints included safety, tolerability, overall response rate, and PFS. Disease response and progression was assessed by investigators using the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin Lymphomas (Cheson 2014) and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Cheson 2016) at Cycle 2 and EOT. Results In Part B, the majority of the 58 pts enrolled were white (86%), not of Hispanic or Latino/a or Spanish origins (79%), and less than 65 years old (95%). Median age was 35 years (range: 19-78 years). Twenty-nine percent of pts had Stage II cHL with bulky mediastinal disease, while the remainder had Stage III (17%) or Stage IV (50%) cHL. Of the 58 pts enrolled, 57 received at least one dose of study treatment. Of the 57 pts who received at least one dose of study treatment, 1 pt discontinued treatment (all study drugs) by the end of Cycle 2 due to treatment-emergent adverse events (TEAEs). By end of Cycle 2, the majority of TEAEs were Grades 1 and 2; 16% of pts experienced ≥Grade 3 TEAEs. Nausea, fatigue, and alopecia were the most frequently reported treatment-related TEAEs (51%, 33%, and 26% of pts, respectively). No febrile neutropenia was observed, and there were no Grade 5 adverse events. Two pts (4%) experienced treatment-related treatment-emergent serious adverse events; 1 pt (2%) experienced hypophysitis and aseptic meningitis, and discontinued treatment, and 1 pt (2%) experienced pneumonitis. Preliminary efficacy results are anticipated for presentation. Conclusions Preliminary results demonstrate that AN+AD is well-tolerated, and no new safety signals were observed. The omission of bleomycin and vinblastine may have contributed to the absence of certain AEs, such as febrile neutropenia. This study of AN+AD is ongoing, and updated safety and efficacy results will be presented at the meeting. Disclosures Lee: BMS: Honoraria, Research Funding; Aptitude Health: Honoraria; Century Therapeutics: Consultancy; Pharmacyclics: Research Funding; Guidepoint: Honoraria; Oncternal: Research Funding; Seagen: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Honoraria. Flinn: Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Melear: Astrazeneca: Speakers Bureau; TG Therapeutics: Speakers Bureau; Janssen: Speakers Bureau. Ramchandren: curis: Research Funding; MERCK: Consultancy, Research Funding; pharmacyclics: Consultancy, Research Funding; seattle genetics: Consultancy, Research Funding; BMS: Consultancy; Trillium: Research Funding. Friedman: Seagen Inc.: Research Funding. Burke: MorphoSys: Consultancy; Beigene: Consultancy, Speakers Bureau; AbbVie: Consultancy; Epizyme: Consultancy; Adaptive Biotechnologies: Consultancy; Bristol Myers Squibb: Consultancy; Kymera: Consultancy; AstraZeneca: Consultancy; Verastem: Consultancy; Kura: Consultancy; X4 Pharmaceuticals: Consultancy; SeaGen: Consultancy, Speakers Bureau; Roche/Genentech: Consultancy. Linhares: Seagen Inc.: Research Funding. Peterson: Seagen Inc.: Research Funding. Raval: Abbvie Pharmaceuticals: Speakers Bureau; Adaptive Biotechnologies: Consultancy; ADCT Therapeutics: Consultancy, Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau; Amgen Biotechnology Company: Research Funding; Astellas Pharmaceuticals: Speakers Bureau; Astrazeneca Pharmaceuticals: Consultancy, Speakers Bureau; Beigene Pharmaceuticals: Speakers Bureau; Bristol Meyers Squibb Pharmaceuticals: Consultancy; Epizyme Pharmaceuticals: Consultancy, Speakers Bureau; Genetech Biotechnology Company: Research Funding; GlaxoSmithKline Pharmaceuticals: Consultancy; Incyte Pharmaceuticals Corporation: Speakers Bureau; Jazz Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy; Morphosys Biotech Company: Speakers Bureau; Sanofi Genzyme: Consultancy; Seagen Biotechnology Company: Research Funding; Takeda Pharmaceuticals: Consultancy, Speakers Bureau. Chintapatla: Seagen Inc.: Research Funding. Feldman: Alexion, AstraZeneca Rare Disease: Honoraria, Other: Study investigator. Yimer: Janssen: Speakers Bureau; Beigene: Speakers Bureau; Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau; GSK: Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Pharmacyclics: Speakers Bureau; Texas Oncology: Current Employment. Islas-Ohlmayer: Seagen Inc.: Research Funding. Dean: Seagen Inc.: Research Funding. Rana: Seagen Inc.: Research Funding. Gandhi: GlaxoSmithKline: Honoraria; Karyopharm Therapeutics: Honoraria; TG Therapeutics: Honoraria. Renshaw: Amgen: Speakers Bureau; SeaGen: Consultancy; Jazz Pharmaceuticals: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Texas Oncology: Current Employment. Gillespie-Twardy: Seagen Inc.: Research Funding. Ho: Seagen Inc.: Current Employment, Current equity holder in publicly-traded company. Fanale: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Guo: Seagen Inc.: Current Employment, Current equity holder in publicly-traded company. Yasenchak: Seagen Inc.: Research Funding.

Background: Human papillomavirus (HPV) testing from clinician-collected cervical and self-collected cervico-vaginal samples is more sensitive for detecting CIN2+/CIN3+ than cytology-based screening, stimulating interest in HPV testing from urine. The objective was to determine the performance of the Trovagene HPV test for the detection of CIN2+ from urine and PreservCyt cervical samples. Methods: Women referred for colposcopy at St Mary's Hospital (London, United Kingdom), following abnormal cytology, were recruited to this diagnostic accuracy study by convenience sampling (September 2011 to April 2013). A total of 501 paired urine and cervical samples were collected. Primary outcomes were sensitivity for CIN2+/CIN3+ and specificity for Results: Trovagene HPV test sensitivity and specificity from PreservCyt were similar to well-established tests [sensitivity for CIN3+ (n = 145) 96.3% (95% confidence interval (CI), 89.6–99.2); CIN2+ (n = 81) 94.5% (95% CI, 89.4–97.6); specificity for Conclusions: Trovagene HPV test's performance on PreservCyt cervical samples was comparable with established HPV tests. Sensitivity in urine, although slightly lower, may nevertheless be adequate for self-sampling. This referral population's higher HPV positivity rate affects specificity, warranting further studies in a screening population. Impact: This may prove useful for women not attending for cervical screening. Cancer Epidemiol Biomarkers Prev; 26(7); 1053–9. ©2017 AACR.

TPS8068 Background: Brentuximab vedotin (BV, ADCETRIS) is approved for the treatment of adults with treatment-naïve Stage III or IV cHL in combination with AVD (Connors 2017). Nivolumab is approved for treatment of adults with relapsed/refractory cHL. Both agents have been well tolerated with promising activity when combined with multi-agent chemotherapy. The combination of BV plus nivolumab was evaluated as a frontline treatment option for patients (pts) with cHL who are over 60 years and ineligible for or declined conventional combination chemotherapy (Friedberg, 2018). The ongoing study reported an ORR of 82% in 11 pts and appears well tolerated in this population. In another trial in 93 patients in the first salvage setting, the combination produced a 67% CR rate (Herrera 2018, Moskowitz 2019) and the majority of patients were able to undergo subsequent stem cell transplant. It is reasonable to expect that the combination of BV, nivolumab, A, and D (AN + AD) will result in high response rates and be well tolerated, with potentially less toxicity. Methods: SGN35-027 (NCT03646123) is a phase 2 study designed to evaluate the efficacy and safety of A+AVD when administered with growth factor prophylaxis in pts with stage III/IV cHL (Part A). Part B will evaluate the combination of AN + AD in a similar patient population. The primary objective of Part B is to estimate the CR rate at EOT in pts with treatment-naïve advanced cHL. Patients in Part B will have Ann Arbor Stage IIB/III/IV cHL or Stage IIA cHL with bulky mediastinal disease. Enrollment is ongoing in both parts of the study. Approximately 50 pts will be enrolled in Part B. All pts will be treated with BV 1.2 mg/kg, nivolumab 240 mg, doxorubicin 25 mg/m2, and dacarbazine 375 mg/m2, administered separately by IV infusion on Days 1 and 15 of each 28-day cycle for up to 6 cycles. Efficacy will be assessed by PET/CT scans at C2 and EOT. Disease assessments will be performed periodically during follow up. Disease response and progression will be assessed using Lugano with the incorporation of LYRIC (Cheson 2016). Clinical trial information: NCT03646123 .

Background Despite the advances in therapy of classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphoma (PTCL) over the years, the outcomes seen in younger patients with the disease have not been attained in patients ≥60 years of age. Studies cite 5-year progression-free survival (PFS) and freedom from treatment failure rates of 30%-45% in older patients with HL, as compared to rates of 75%-80% expected in younger patients (Evens 2008; Proctor 2009). In a recent retrospective study of patients >60 years of age diagnosed with PTCL between 2008-2014, a multivariate analysis demonstrated that a Charlson Comorbidity Index (CCI) ≥2 and high IPI score (3-5) were independent risk factors for worse overall survival (OS) and PFS (Zhao 2016). Similarly, multivariate analysis of registry data from Sweden shows that a CCI ≥2, when adjusted for age, is independently associated with worse OS and PFS outcomes (Ellin 2018). There is no standard treatment regimen for elderly patients with cHL and PTCL, and co-morbidities including depressed cardiac and renal function limit the ability to use combination chemotherapy, and represent a high unmet need. Brentuximab vedotin (BV, ADCETRIS®) is a CD30-directed antibody-drug conjugate (ADC) consisting of the chimeric IgG1 antibody cAC10, specific for human CD30; the microtubule-disrupting agent monomethyl auristatin E (MMAE); and a protease-cleavable linker that covalently attaches MMAE to cAC10. Following the binding of BV to CD30-expressing cells, the ADC-CD30 complex is internalized, and MMAE released via proteolytic cleavage. Binding of MMAE to tubulin disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptosis. Single-agent BV has demonstrated robust activity in patients with HL refractory to several lines of chemotherapy and the ECHELON-1 study (Connors 2017) established its efficacy in combination with chemotherapy for the front line treatment of HL. In a phase 2 study of single-agent BV in 27 patients aged ≥ 60 years with HL, there was an objective response rate of 92%, with 73% achieving complete remission (Forero-Torres, 2015). For CD30-expressing PTCL, single-agent BV is an active and well-tolerated treatment for patients with relapsed or refractory disease (Horwitz 2014) and the ECHELON-2 study showed that the addition of BV to combination chemotherapy in the frontline treatment improves both PFS and OS (Horwitz 2018). In the elderly patient populations who are not candidates for multi-agent chemotherapy, frontline treatment with single-agent BV may have the potential to be an active and well-tolerated treatment. Study Design Two additional cohorts have been added to the SGN35-015 phase 2 open-label study (NCT01716806) to evaluate the efficacy and tolerability of BV as monotherapy in treatment-naive patients with cHL, which excludes nodular lymphocyte-predominant HL (Part E) or treatment-naive patients with CD30-expressing PTCL (Part F). The primary objective of these cohorts is to assess objective response rates of single-agent BV as frontline therapy in patients ≥60 years of age and ineligible for conventional chemotherapy for HL (Part E) or CD30-expressing PTCL (Part F). Eligible patients in Parts E and F must be ≥75 years or ≥60 years of age and have one of the following: confirmed ejection fraction Approximately 30 evaluable patients will be enrolled in Parts E and F of the study and administered BV 1.8 mg/kg as a single intravenous infusion on Day 1 of each 21-day cycle. Patients achieving a complete remission, partial remission, or stable disease will receive up to 16 cycles of treatment. Treatment response will be assessed by spiral CT scans of the chest, abdomen, and pelvis and PET scans at Cycles 2, 6, and 11. Response assessment will be determined by blinded independent central review. Disclosures Yasenchak: BMS: Consultancy; Seattle Genetics: Consultancy. Bordoni:Phillips & Gilmore: Honoraria; Genentech: Speakers Bureau; Merck: Speakers Bureau; Seattle Genetics, Inc.: Research Funding; Practice Point Communication: Honoraria; Deciphera: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Honoraria; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Yazbeck:Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Research Funding. Patel-Donnelly:Seattle Genetics, Inc.: Research Funding. Larson:Seattle Genetics, Inc.: Research Funding. Newhook:Seattle Genetics, Inc.: Employment. Ho:Seattle Genetics, Inc.: Employment, Equity Ownership. Mei:Seattle Genetics, Inc.: Research Funding.

Background. In patients with Hodgkin lymphoma (HL) aged ≥60 years, comorbidities and treatment-related toxicities often prevent delivery of optimal intensity and/or duration of standard frontline chemotherapy. Brentuximab vedotin (BV) and nivolumab (Nivo) have two distinct mechanisms of action, tolerability of the combination has been observed in relapsed/refractory HL in a phase 1/2 study (85% objective response rate [ORR]; 62% complete remission [CR] rate) (Herrera 2017); thus, our phase 2 study was amended to evaluate this combination in a cohort of newly diagnosed HL patients aged ≥60 years (NCT01716806). Methods. Eligible subjects have treatment-naive classical HL and are ineligible for or declined initial conventional combination chemotherapy (planned N = 20). Subjects received BV 1.8 mg/kg + Nivo 3 mg/kg as well as prophylactic premedication for infusion-related reactions on Day 1 of each 3-week cycle for ≤16 cycles. CT/PET scans were performed at Cycles 2 (CT only), 4, 8, 12, and 16 (assessed per Lugano Classification Revised Staging System [Cheson 2014] and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) [Cheson 2016]). The primary objective is ORR. Results. Twenty-one subjects received BV + Nivo (median age, 72 years [range, 60-88]). The majority had an ECOG performance status of 0/1 (95%), Stage III/IV disease (77%), and presented with B symptoms at baseline (57%). In this elderly population, 48% had bulky disease and 38% had extranodal disease at the initial diagnosis. Of the 21 subjects treated, 7 remain on treatment, 2 discontinued treatment due to progressive disease, 6 completed treatment, 4 withdrew due to subject decision, 1 withdrew due to pneumocystis jiroveci pneumonia, and 1 had an unrelated Grade 3 serious adverse event of acute renal failure and sepsis, resulting in death. The most common treatment-related adverse events (TRAE) of any grade were fatigue (48%), peripheral sensory neuropathy (38%), diarrhea, infusion-related reactions, and pyrexia (24% each). No infusion-related reactions required steroid intervention. Among TRAE ≥Grade 3, the most common were elevated lipase (19%) and peripheral motor neuropathy (14%). Three subjects had immune-related AEs with a maximum severity of Grade 3. Three of the 21 subjects treated were not evaluable for efficacy, defined in the protocol as subjects who had both a baseline and at least one post-baseline disease assessment or who had documented progression of disease any time after receiving any amount of BV. Non-evaluable subjects included 1 who died from renal failure prior to assessment, 1 who withdrew consent prior to assessment, and 1 who had not been assessed at the time of the data cutoff. Based on the 18 evaluable subjects, the ORR was 100%, with a 72% CR rate and a 28% PR rate. Conclusions. Elderly HL remains an unmet clinical need. These data suggest that BV + Nivo is an active treatment with an encouraging CR rate (72%) and appears well tolerated in these patients. These results also suggest that with further follow-up and validation, treatment with BV + Nivo may improve patient outcomes. Enrollment in this cohort is complete (21 subjects), with 7 subjects continuing to receive treatment. Disclosures Yasenchak: BMS: Consultancy; Seattle Genetics: Consultancy. Bordoni:Seattle Genetics, Inc.: Research Funding; Practice Point Communication: Honoraria; Phillips & Gilmore: Honoraria; Merck: Speakers Bureau; Genentech: Speakers Bureau; Deciphera: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Honoraria; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Yazbeck:Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Patel-Donnelly:Seattle Genetics, Inc.: Research Funding. Anderson:Seattle Genetics, Inc.: Research Funding. Larson:Seattle Genetics, Inc.: Research Funding. Newhook:Seattle Genetics, Inc.: Employment. Mei:Seattle Genetics, Inc.: Research Funding. Ho:Seattle Genetics, Inc.: Employment, Equity Ownership. Friedberg:Bayer: Honoraria, Other: Data & Safety Monitoring Committee; Acerta: Other: Data & Safety Monitoring Committee.

Background For patients with advanced classical Hodgkin lymphoma (cHL), the most common frontline regimen has historically consisted of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), which originated in 1975 (Connors 2018). However, up to 30% of patients treated with ABVD as frontline therapy will relapse or are refractory to treatment (Canellos 1992; Carde 2016; Gordon 2013). Additionally, bleomycin is associated with potentially fatal pulmonary toxicity (Canellos 2004; Martin 2004), and vinblastine is associated with neutropenia and peripheral neuropathy. Brentuximab vedotin (BV, ADCETRIS®) has been approved for the treatment of adult patients with previously untreated Stage III or IV cHL in combination with doxorubicin, vinblastine, and dacarbazine based on the results of the ECHELON-1 study (Connors 2017). Data reported from ECHELON-1 showed patients randomized to the BV + doxorubicin, vinblastine, and dacarbazine (A + AVD) treatment arm had a statistically significant 23% risk reduction in modified PFS events vs patients randomized to the ABVD arm of the study. The combination of BV plus nivolumab was reported as showing potential for the treatment of cHL. The combination was evaluated as a potential frontline treatment option for patients with cHL who are over 60 years of age and ineligible for or declining conventional combination chemotherapy (Friedberg, 2018). The ongoing study reported an ORR of 82% in 11 patients and the regimen appears well tolerated in this population. In another trial in 62 patients in the first salvage setting, the combination produced a 61% CR rate (Herrera 2018) and the patients were able to undergo subsequent stem cell transplant. BV and nivolumab have been combined separately with doxorubicin, vinblastine, and dacarbazine and shown to be active and well tolerated. Furthermore, BV has been evaluated in combination with just doxorubicin and dacarbazine, omitting vinblastine, in 34 patients with previously untreated non-bulky stage I/II cHL and showed 100% complete response rate at end of treatment (EOT) and PFS and OS rates of 100% at last follow up (median=15 months; Abramson 2018). This combination resulted in a low incidence of neutropenia and alopecia, and moderate (Grade 1 or 2) peripheral neuropathy. It is therefore reasonable to expect that the combination of BV, nivolumab, doxorubicin, and dacarbazine (AN + AD) will result in high response rates and be well tolerated, with potentially less toxicity. Study Design SGN35-027 (NCT03646123) is a phase 2 study designed to evaluate growth factor prophylaxis plus BV in combination with AVD in patients with stage III and IV cHL (Part A). A second cohort has been added to the study (Part B), which will evaluate the combination of AN + AD in this patient population. The primary objective of Part B is to estimate the CR rate at EOT with AN + AD in patients with previously untreated advanced cHL. All enrolled patients will be 12 years or older, with an ECOG performance status of ≤2. Patients in Part B will be treatment-naïve with Ann Arbor Stage IIB/III/IV cHL or Stage IIA cHL with bulky disease. Patients must have bidimensional measurable disease, as documented by radiographic technique, and qualifying baseline laboratory data. Patients will be excluded if they have nodular lymphocyte predominant HL or have symptomatic neurologic disease that compromises normal activities of daily living or requires medication. Patients with known cerebral or meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy, will also be excluded. Approximately 50 patients will be enrolled in Part B. All patients will be treated with BV 1.2 mg/kg, nivolumab 240 mg, doxorubicin 25 mg/m2, and dacarbazine 375 mg/m2. All study drugs will each be administered separately by IV infusion on Days 1 and 15 of each 28-day cycle for up to 6 cycles of treatment. Efficacy will be assessed by PET and CT scans at Cycle 2 and EOT. Disease assessments will be performed during follow-up every 3 months for the first year, every 6 months for 2 additional years, and then per institutional standard of care. Disease response and progression will be assessed by investigators using the Lymphoma Response to Immunomodulatory Therapy Criteria modification of Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2016). Disclosures Friedman: Amgen: Speakers Bureau; Celgene: Speakers Bureau; Seattle Genetics, Inc.: Research Funding. Lee:Seattle Genetics, Inc.: Research Funding. Ho:Seattle Genetics, Inc.: Employment, Equity Ownership. Flinn:AbbVie, Seattle Genetics, TG Therapeutics, Verastem: Consultancy; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Genentech, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Janssen, Karyopharm Therapeutics, Kite Pharma, Novartis, Pharmacyclics, Portola Pharmaceuticals: Research Funding.