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Introduction: Prognosis remains poor for patients (pts) with R/R cHL who relapse after or are ineligible for autologous stem cell transplant (ASCT). Programmed death 1 (PD-1) inhibitors are an effective therapeutic option for such pts. Previous analyses from the phase 2 KEYNOTE-087 (NCT02453594) trial demonstrated that monotherapy with the PD-1 inhibitor pembrolizumab (pembro) had effective antitumor activity and acceptable safety in pts with R/R cHL, leading to FDA approval for adult and pediatric pts with R/R cHL who relapsed after ≥3 prior lines of therapy. However, durability of response after pembro, its relationship with response depth, and safety of treatment discontinuation for pts achieving complete response (CR) remain salient clinical questions. We present efficacy and safety from KEYNOTE-087 after ~5 y of follow-up. Methods: Pts with R/R cHL that progressed after ASCT and subsequent brentuximab vedotin (BV, cohort 1), progressive disease (PD) after salvage chemotherapy and BV therapy without ASCT (cohort 2), or PD after ASCT without subsequent BV therapy (cohort 3) received pembro 200 mg every 3 wks for up to 2 y. Pts who discontinued treatment after initial CR and relapsed were eligible to receive up to 17 additional cycles (~1 y) of pembro (2nd course). Primary end points: ORR per blinded independent central review (BICR), and safety. Additional end points: ORR per Lugano classification, DOR, and PFS by BICR; OS and 2nd-course ORR per investigator. DOR, PFS, and OS were estimated by Kaplan-Meier (K/M) method. Data cutoff was March 15, 2021. Results: At data cutoff, median time from first dose to date of death or data cutoff was 62.9 mo (range, 1.0-68.7). In the total population (N=210), 46 pts completed 2 y of treatment and 164 pts discontinued (primarily due to progressive disease [n=86]). ORR was 71.0% (95% CI, 64.8-77.4; CR, 27.6%; partial response [PR, 43.8%]); results were similar per Lugano classification (ORR, 73.3% [95% CI, 66.8-79.2]; CR, 32.9%; PR, 40.5%). ORR was 84.1% (CR, 36.2%; PR, 47.8%) in cohort 1 (n=69), 67.9% (CR, 28.4%; PR, 39.5%) in cohort 2 (n=81), and 68.3% (CR, 35.0%; PR, 33.3%) in cohort 3 (n=60). In the total population, median DOR was 16.6 mo (95% CI, 11.8-27.1). Four pts (24.8% per K/M method; cohort 1, n=1; cohort 2, n=0; cohort 3, n=3) had response ≥60 mo. In the total population, median PFS was 13.7 mo (95% CI, 11.1-19.4) and the 5-y PFS rate was 14.2%: 16.4 mo (95% CI, 11.3-27.6) in cohort 1, 11.1 mo (95% CI, 7.5-13.7) in cohort 2, and 19.7 mo (95% CI, 10.8-27.3) in cohort 3. In the total population, median OS was not reached (NR) and the 5-y OS rate was 70.7%: 71.3% in cohort 1, 69.2% in cohort 2, and 71.5% in cohort 3. Of 58 pts in the total population who achieved CR (Table), median DOR was NR (95% CI, 16.1-NR) and 4 pts (51.6% per K/M method; cohort 1, n=1; cohort 2, n=0; cohort 3, n=3) had a response ≥60 mo. Median PFS was 56.5 mo (95% CI, 21.7-NR) and 5-y PFS rate was 44.3%; median OS was NR and 5-y OS rate was 82.8%. Ten pts with CR received allogeneic stem cell transplant (allo-SCT) and 48 pts with CR did not undergo allo-SCT. Of 20 pts who received 2nd-course treatment (cohort 1, n=10; cohort 2, n=7; cohort 3, n=3), 10 pts (cohort 1, n=2; cohort 2, n=6; cohort 3, n=2) completed 17 additional cycles of treatment; 1 pt each from cohort 1 and cohort 3 were mid-treatment. ORR based on 19 evaluable pts from cohorts 1-3 was 73.7% (95% CI, 48.8-90.9). Median DOR for 2nd course was 15.2 mo (95% CI, 3.9-32.9), and 1 pt (13.7%) had a second response ≥36 mo. Treatment-related adverse events (AEs) of any grade occurred in 72.9% of pts; most common (>10%) were hypothyroidism (14.3%), pyrexia (11.4%), and fatigue (11.0%). Grade 3-4 treatment-related AEs occurred in 12.9% of pts; neutropenia (n=5), diarrhea and pericarditis (n=2, each) occurred in ≥2 pts. All-cause grade 5 AEs (n=3) were due to acute graft-versus-host disease, infection, and septic shock; these AEs were not considered treatment related. Conclusions: With median of follow-up >5 y, pembro monotherapy demonstrated sustained antitumor activity in pts with R/R cHL. ORRs were high and responses durable in the overall population and in those with varied treatment histories. Pts with CR had especially durable responses, and in those relapsing from CR, 2nd-course pembro frequently re-induced sustained response. Safety was manageable with no new signals. Figure 1 Figure 1. Disclosures Armand: Merck & Co., Inc.: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Celgene: Consultancy; Morphosys: Consultancy; Daiichi Sankyo: Consultancy; Miltenyi: Consultancy; Tessa: Consultancy; GenMab: Consultancy; C4: Consultancy; Enterome: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding; Otsuka: Research Funding; Sigma Tau: Research Funding; IGM: Research Funding; Kite: Research Funding. Zinzani: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lee: Oncternal: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Seagen: Research Funding; Century Therapeutics: Consultancy; Guidepoint: Honoraria; Aptitude Health: Honoraria; BMS: Honoraria, Research Funding; Janssen: Honoraria; Pharmacyclics: Research Funding. Johnson: AbbVie: Consultancy, Research Funding; Merck: Consultancy; Roche: Consultancy, Honoraria; BMS: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy. Brice: MSD: Research Funding; Amgen: Other: Travel/accommodations/expenses; Takeda: Research Funding; Roche: Other: Travel/accommodations/expenses. Radford: Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Current holder of individual stocks in a privately-held company; ADC Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Honoraria, Speakers Bureau; BMS: Honoraria. Ribrag: Roche: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Molin: Roche: Honoraria; MSD: Honoraria; BMS: Honoraria; Takeda: Honoraria. Vassilakopoulos: AbbVie: Consultancy, Honoraria; GlaxoSmithKline: Honoraria, Other: Travel; Amgen: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Merck: Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria, Other: Travel; Roche: Consultancy, Honoraria, Other: Travel; Takeda: Consultancy, Honoraria, Other: Travel, Research Funding; Integris: Honoraria; AstraZeneca: Honoraria; Pfizer: Research Funding; Dr. Reddy's: Research Funding; Karyopharm: Research Funding. Tomita: Kyowa Kirin: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria, Research Funding; Astellas Pharma: Honoraria, Research Funding; Nippon Shinyaku: Consultancy, Honoraria, Research Funding; Janssen Pharmaceutical: Honoraria; Zenyaku Kogyo: Honoraria; AbbVie GK: Honoraria; Bristol Myers Squibb: Honoraria; SymBio Pharmaceutical: Consultancy, Honoraria; Otsuka Pharmaceutical: Research Funding; Ono Pharmaceutical: Research Funding; Shionogi: Research Funding; Suitomo Dainippon Pharma: Research Funding; Taiho Pharmaceutical: Research Funding; Teijin: Research Funding; Pfizer Japan: Research Funding; Mochida Pharmaceutical: Research Funding; Yakult Honsya: Research Funding; Perseus Proteomics: Research Funding. von Tresckow: Pentixafarm: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; AstraZeneca: Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Kite-Gilead: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; AbbVie: Other: congress and travel support. Shipp: Bristol Myers Squibb: Research Funding; Merck: Research Funding; AstraZeneca: Consultancy, Research Funding; Immunitas Therapeutics: Consultancy; Abbvie: Other: Institution: Research Grant/Funding; Bayer: Other: Institution: Research Grant/Funding. Herrera: Genentech: Consultancy, Research Funding; Karyopharm: Consultancy; Seagen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Takeda: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Kite, a Gilead Company: Research Funding; Gilead Sciences: Research Funding; Merck: Consultancy, Research Funding; Tubulis: Consultancy. Lin: Merck (MSD): Current Employment. Kim: Merck: Current Employment, Other: Current Stockholder. Chakraborty: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Moskowitz: Merck & Co., Inc.: Research Funding.

Background: Immunotherapeutic strategies targeting the PD-1/PD-L1 pathway have become part of standard of care for patients with classical Hodgkin lymphoma (cHL). Recent studies have investigated combinations of anti-PD-1 antibodies with conventional chemotherapy and demonstrated significant clinical benefits in the first-line setting. A phase 2 trial demonstrated that induction with pembrolizumab monotherapy followed by chemotherapy was highly effective and safe in patients with newly diagnosed, early unfavorable, or advanced-stage cHL (Allen PB et al. Blood. 2020;137[10]:1318-1326). The KEYNOTE-C11 open-label phase 2 study will build on this concept by evaluating the safety and efficacy of sequential pembrolizumab monotherapy and chemotherapy followed by pembrolizumab consolidation in adult patients with newly diagnosed, early unfavorable, or advanced-stage cHL. Study Design and Methods: Patients must have newly diagnosed, histologically confirmed, untreated (no prior chemotherapy, immunotherapy, or other systemic therapy for cHL), early unfavorable cHL (Ann Arbor stage I/II plus ≥1 National Comprehensive Cancer Network unfavorable risk factor) or advanced-stage cHL (Ann Arbor stage III/IV) and measurable disease per Lugano 2014 classification. Approximately 140 patients will be enrolled. All patients will receive pembrolizumab 200 mg IV every 3 weeks (Q3W) for 3 cycles followed by PET to determine response to pembrolizumab monotherapy. After pembrolizumab induction, all patients will receive 2 cycles of AVD (day 1 and day 15 Q4W) and undergo another assessment by PET (PET 3) to determine the next treatment course. Patients with negative findings on PET 3 (≤3 on the Deauville 5-point scale) will receive 2-4 additional cycles of AVD, depending on stage and bulk of disease; those with nonbulky early unfavorable disease will receive 2 cycles, and all others will proceed to 4 cycles of AVD chemotherapy. Patients who are PET 3+ (≥4 on the FDG-PEG 5-point scale) and aged Disclosures Winter: Epizyme: Other: Husband: Data and Safety Monitoring Board; Agios: Other: Husband: Consultancy; Gilead: Other: Husband: Consultancy; Janssen: Other: Husband: Consultancy; Actinium Pharma: Consultancy; BMS: Other: Husband: Data and Safety Monitoring Board; Ariad/Takeda: Other: Husband: Data and Safety Monitoring Board; Merck: Consultancy, Honoraria, Research Funding; Novartis: Other: Husband: Consultancy, Data and Safety Monitoring Board; Karyopharm (Curio Science): Honoraria. Nahar: Merck: Current Employment. Kim: Merck: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder.

Background: The T-cell immunoglobulin and ITIM domain (TIGIT) is highly coexpressed with programmed cell death 1 (PD-1) on both CD4 and CD8 T cells in cancers. Blockade of TIGIT with vibostolimab (MK-7684) has demonstrated antitumor activity in multiple preclinical tumor models. Inhibition of the PD-1 pathway with pembrolizumab has demonstrated efficacy and safety in several hematologic malignancies. Enhanced antitumor activity with anti-TIGIT and anti-PD-L1 combination therapy has been seen in a preclinical model. A multicohort, open-label, phase 2 study will evaluate the safety and efficacy of MK-7684A, a coformulation of vibostolimab and pembrolizumab, in patients with relapsed or refractory (r/r) hematologic malignancies. Study Design and Methods: This two-part phase 2 study includes a signal-finding phase (part 1) with the option for a dose-expansion phase (part 2), depending on the observed risk-benefit profile from part 1. Patients must have confirmed diagnosis of r/r disease, including classical Hodgkin lymphoma (cHL; cohort A or B), primary mediastinal B-cell lymphoma (PMBCL; cohort A or B), follicular lymphoma (FL; cohort C), diffuse large B-cell lymphoma (DLBCL; cohort D), multiple myeloma (MM; cohort E), or non-Hodgkin lymphoma (NHL; cohort F) (Table 1). Three hundred thirty participants are expected to enroll in part 1 (signal finding) and part 2 (cohort expansion). In part 1, patients in cohorts A-F will receive MK-7684A (vibostolimab 200 mg + pembrolizumab 200 mg) by IV infusion every 3 weeks (Q3W) for up to 35 cycles. Patients will continue treatment until investigator-determined PD, start of new anticancer treatment, documented complete response, or completion of maximum 35 cycles of treatment. Safety data from the first 12 treated patients from any cohort will be collected. Dose-limiting toxicities (DLTs) will be monitored for the first 6 weeks of continuous treatment. If ≥5 of the 12 patients experience DLTs during this period, enrollment may be discontinued. After the DLT review period, safety data will be collected every 6 months for all enrolled patients. Efficacy assessments will be performed Q3W, with the initial tumor imaging performed ≤28 days after enrollment and repeated at 12 weeks (cohorts A-D, F) or 4 weeks (cohort E) after enrollment. Adverse events (AEs) will be monitored throughout the study, and severity will be graded according to the guidelines outlined in NCI CTCAE version 5.0. Each patient will be monitored for AEs and serious AEs for 30 day and 90 days, respectively, after discontinuation of study intervention. The primary end point for part 1 is the number and proportion of patients with DLTs, AEs, and discontinuations from study treatment due to AEs. Safety and tolerability will be assessed by clinical review. Secondary end points include investigator-assessed objective response rate, investigator-assessed duration of response, disease control rate, and pharmacokinetic end points. Overall survival, progress-free survival, health-related quality of life assessments, and molecular assessments will be exploratory. In the part 2 dose-expansion phase, the plan is to enroll approximately 120 patients from cohorts B-E to receive up to 35 cycles of MK-7684A Q3W; 30 additional patients may be enrolled in a cohort expansion (cohort G) to receive vibostolimab monotherapy Q3W for up to 35 cycles. Cohort G will include patients with cHL or PMBCL with PD after ≥2 or ≥3 prior therapies, FL after ≥2 prior therapies, DLBCL after ≥2 prior therapies, and/or MM after ≥3 prior therapies. Figure 1 Figure 1. Disclosures Yusuf: Merck & Co., Inc.: Current Employment. Jemielita: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder.

Introduction: Similar to classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma (PMBCL) expresses high level of the programmed cell death 1 (PD-1) ligands: PD-L1 and PD-L2. Prior analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated that monotherapy with the PD-1 inhibitor pembrolizumab had effective antitumor activity and acceptable safety in relapsed/refractory (R/R) PMBCL, leading to FDA approval for adult patients with R/R PMBCL after ≥2 prior therapies. Long-term durability of response with PD-1 blockade in patients with PMBCL, especially those who achieve complete remission (CR), remains a critical clinical question. Here we present updated efficacy and safety of patients with R/R PMBCL in KEYNOTE-170 after ~4 years of follow-up. Methods: Patients with R/R PMBCL who progressed after or were ineligible for autologous stem cell transplant and received ≥2 prior therapies received pembrolizumab 200 mg every 3 weeks (Q3W) for up to 35 cycles (~2 years). Response assessments were Q12W per 2007 Revised Response Criteria for Malignant Lymphomas. End points included overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR) by investigator assessment; as well as overall survival (OS) and safety. Data cutoff date was October 23, 2020. Results: At data cutoff, the median duration of follow-up was 48.7 months (range,41.2-56.2). Baseline characteristics of the patients have been previously described (Armand P, et al. J Clin Oncol. 2019; 37(34): 3291-3299). Among all treated patients (N=53), 13 completed 2 years of treatment and 40 patients discontinued, primarily due to progressive disease (n=18). ORR per investigator assessment was 41.5% (95% CI, 30.0-53.7), with 20.8% complete response rate and 20.8% partial response rate. Median DOR was not reached (NR) and 80.6% of patients had a response ≥48 months. Median PFS was 4.3 months (95% CI, 2.8-13.8) and the 48-month PFS rate was 33.0%. Median OS was 22.3 months (95% CI, 7.3-NR) and the 48-month OS rate was 45.3%. At data cutoff, treatment-related adverse events (AEs) of any grade occurred in 30 patients (56.6%); the most commonly reported (incidence >5%) were neutropenia (18.9%), asthenia (9.4%), hypothyroidism (7.5%), and fatigue and pyrexia (5.7% each). Grade 3-4 treatment-related AEs occurred in 22.6% of patients; only neutropenia (n=7) occurred in ≥2 patients. No grade 5 treatment-related AEs occurred. Conclusions: With 48.7 months of follow-up in heavily pretreated participants with R/R PMBCL, treatment with pembrolizumab monotherapy continued to demonstrate sustained antitumor activity. PFS and OS demonstrated promising trends for long-term survival with no new safety signals identified. Disclosures Zinzani: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Thieblemont: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Bouabdallah: Sandoz: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Abbvie: Honoraria; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Waleswski: Roche: Consultancy, Honoraria, Other: Institution: Research Grant/Funding; Takeda: Consultancy, Honoraria; Servier: Honoraria; Gilead: Consultancy, Honoraria; Amgen: Honoraria; Novartis: Consultancy, Honoraria; GSK/Novartis: Other: Institution: Research Grant/Funding; Abbvie: Consultancy, Honoraria. Fogliatto: AstraZeneca: Speakers Bureau. Martin Garcia-Sancho: Celgene: Honoraria, Other: travel; Celgene/BMS: Consultancy; Janssen: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Gilead: Consultancy, Honoraria; Morphosys: Consultancy; Kyowa Kirin: Consultancy; Clinigen: Consultancy; Eusa Pharma: Consultancy; Novartis: Consultancy; Takeda: Honoraria; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Incyte: Consultancy; Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Christian: Celgene/BMS: Other: Institution: Research Grant/Funding; Acerta: Other: Institution: Research Grant/Funding; Seattle Genetics: Consultancy, Other: Institution: Research Grant/Funding; Genentech: Consultancy, Other: Institution: Research Grant/Funding; AstraZeneca: Consultancy; VeraStem: Consultancy; Morphosys: Consultancy, Other: Institution: Research Grant/Funding; Triphase: Other: Institution: Research Grant/Funding; Millenium: Other: Institution: Research Grant/Funding; Immunomedics: Other: Institution: Research Grant/Funding; Merck: Other: Institution: Research Grant/Funding. Özcan: Amgen: Honoraria, Other: Travel/Accommodations/Expenses; Janssen: Other: Travel/Accommodations/Expenses, Research Funding; Celgene: Research Funding; Archigen: Research Funding; Roche: Other: Travel/Accommodations/Expenses, Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Takeda: Honoraria, Other: Travel/Accommodations/Expenses, Research Funding; Pfizer: Research Funding; BMS: Other: Travel/Accommodations/Expenses; Abbvie: Other: Travel/Accommodations/Expenses, Research Funding; Jazz: Other: Travel/Accommodations/Expenses; Abdi Ibrahim: Other: Travel/Accommodations/Expenses; Sanofi: Other: Travel/Accommodations/Expenses; MSD: Research Funding. Perini: Takeda: Speakers Bureau; Roche: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Abbvie: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau. Salles: Debiopharm: Consultancy; Incyte: Consultancy; Morphosys: Consultancy, Honoraria; Janssen: Consultancy; Epizyme: Consultancy, Honoraria; Rapt: Consultancy; Loxo: Consultancy; Ipsen: Consultancy; Miltneiy: Consultancy; Regeneron: Consultancy, Honoraria; Allogene: Consultancy; Velosbio: Consultancy; Takeda: Consultancy; Genmab: Consultancy; Genentech/Roche: Consultancy; Kite/Gilead: Consultancy; Novartis: Consultancy; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria. Shipp: Bayer: Other: Institution: Research Grant/Funding; AstraZeneca: Consultancy, Research Funding; Abbvie: Other: Institution: Research Grant/Funding; Immunitas Therapeutics: Consultancy; Merck: Research Funding; Bristol Myers Squibb: Research Funding. Thompson: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Chakraborty: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Armand: Merck: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Celgene: Consultancy; Morphosys: Consultancy; Daiichi Sankyo: Consultancy; Miltenyi: Consultancy; Tessa: Consultancy; GenMab: Consultancy; C4: Consultancy; Enterome: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding; Otsuka: Research Funding; Sigma Tau: Research Funding; IGM: Research Funding; Kite: Research Funding.

Introduction: Allogeneic stem cell transplant (allo-SCT) and checkpoint blockade both have efficacy in some lymphoid malignancies. However, the safety of allo-SCT after programmed cell death 1 (PD-1) blockade in these patients (pts) remains a question of high clinical interest. We present data from an analysis from 4 KEYNOTE phase 1-3 studies to assess the incidence and severity of complications in pts who received allo-SCT following pembrolizumab therapy. Methods: The analysis included pts with a known transplant date who received an allo-SCT within 2 years of the last dose of study pembrolizumab from the KEYNOTE-013 (NCT01953692, n=20), KEYNOTE-087 (NCT02453594, n=31), KEYNOTE-170 (NCT02576990, n=5), and KEYNOTE-204 (NCT02684292, n=14) trials. Descriptive statistics were used for prespecified complications of interest following allo-SCT. The cumulative incidence of acute grade 2-4 graft versus host disease (GVHD), acute grade 3-4 GVHD, and chronic GVHD was estimated. The corresponding competing risk events were death without acute grade 2-4 GVHD, death without acute grade 3-4 GVHD, and death without chronic GVHD, respectively. In addition, the cumulative incidence of transplant related mortality (TRM) post-allo-SCT was estimated with relapse as a competing risk. The Kaplan-Meier method was used for estimation of progression-free survival (PFS) and overall survival (OS). Results: Seventy patients were evaluable for this analysis. Median age was 30 y (range, 18-65), 57 (81.4%) had classical Hodgkin lymphoma, and the rest had non-Hodgkin lymphoma. Sixty-nine pts (98.6%) received pembrolizumab monotherapy and the remainder received pembrolizumab in combination with lenalidomide. Median duration on study treatment was 5.34 months (range, 0.72-29.60) and median time from last pembrolizumab dose to first allo-SCT was 4.6 months (range, 1-20). Post-pembrolizumab and before allo-SCT, 49 pts (70.0%) had intervening anticancer regimen; 34 (48.6%) had active disease, 31 pts (44.3%) were in remission at time of transplant, and 5 pts (7.1%) had unknown disease status. Forty-four pts (62.9%) received reduced-intensity conditioning, 25 pts (35.7%) received full-intensity conditioning, and 1 pt (1.4%) had missing data. In terms of donor source, 31.4% were haploidentical, 25.7% matched sibling, 31.4% matched unrelated. A total of 55 pts (78.6%) developed GVHD, 54.3% with acute GVHD and 24.3% with chronic GVHD. The estimated cumulative incidence was 0.41 (95% CI, 0.30-0.53) for grade 2-4 acute GVHD and 0.20 (95% CI, 0.12-0.30) for grade 3-4 acute GVHD, both at 6 months post-allo-SCT and was 0.21 (95% CI, 0.12-0.31) for chronic GVHD at 1 year post-allo-SCT. Common sites affected by chronic GVHD were skin, liver, and oral mucosa. Other predetermined complications, including critical illness, immune-mediated adverse events, pulmonary complications, and venoocclusive liver disease, occurred in 32 pts (45.7%). With a median follow-up, defined as the time from allo-SCT to data cutoff or death, of 30.9 months (range, 0.85-71.2) , the post-allo-SCT median PFS was not reached (NR) (95% CI, 14.5-NR) and the 30-month post-allo-SCT PFS rate was 56.8% (95% CI, 42.9-68.5) (Figure A); median overall survival (OS) was NR (95% CI, NR-NR) and the OS rate at 12 months was 82.2% (Figure B). The estimated cumulative incidence for TRM at 18-month post-allo-SCT was 0.11 (95% CI, 0.05-0.21). Conclusions: The incidence of acute and chronic GVHD in this population seems similar to that from historical data (40%-72% and 30%-70%, respectively), although the incidence of severe acute GVHD may be higher than a typical modern allo-SCT series. Despite this, the TRM was low. Furthermore, PFS in the subgroup of pts with cHL was favorable compared to historical series of pts without prior PD-1 blockade, which is consistent with other studies in this population. Altogether, this analysis provides reassurance that allo-SCT is feasible for pts after PD-1 blockade, with PFS and OS outcomes that may in fact be better than historical benchmarks. Figure 1 Figure 1. Disclosures Armand: Merck: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Celgene: Consultancy; Morphosys: Consultancy; Daiichi Sankyo: Consultancy; Miltenyi: Consultancy; Tessa: Consultancy; GenMab: Consultancy; C4: Consultancy; Enterome: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding; Otsuka: Research Funding; Sigma Tau: Research Funding; IGM: Research Funding; Kite: Research Funding. Kuruvilla: Incyte: Honoraria; Gilead: Honoraria; Novartis: Honoraria; AbbVie: Honoraria; TG Therapeutics: Honoraria; Seattle Genetics: Honoraria; Roche: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Janssen: Honoraria, Research Funding; Merck: Honoraria; Karyopharm: Honoraria, Other: Data and Safety Monitoring Board; AstraZeneca: Honoraria, Research Funding; Antengene: Honoraria; Medison Ventures: Honoraria. Herrera: ADC Therapeutics: Consultancy, Research Funding; Kite, a Gilead Company: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Gilead Sciences: Research Funding; Seagen: Consultancy, Research Funding; Tubulis: Consultancy; Takeda: Consultancy; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Karyopharm: Consultancy. Ribrag: Argen-X: Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; GSK: Research Funding; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Brice: Takeda: Research Funding; Amgen: Other: Travel/accommodations/expenses; Roche: Other: Travel/accommodations/expenses; MSD: Research Funding. Thieblemont: Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Von Tresckow: Pentixafarm: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Congress and travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; AstraZeneca: Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding. Kim: Merck: Current Employment, Other: Current Stockholder. Orlowski: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Chakraborty: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Zinzani: Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction: The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a transmembrane protein that is overexpressed in multiple cancers, including hematological malignancies. Zilovertamab vedotin (MK-2140) is an antibody -drug conjugate comprising a humanized IgG1 monoclonal antibody, a proteolytically cleavable linker, and the antimicrotubule cytotoxic agent monomethyl auristatin E (MMAE). Preclinical evidence demonstrated the cytotoxicity of zilovertamab vedotin in hematologic cell lines. This first human phase 1 dose escalation study (NCT03833180) evaluated the safety and efficacy of zilovertamab vedotin at various doses in patients with relapsed/refractory hematologic malignancies. Methods: Eligible patients aged ≥18 years with an Eastern Cooperative Oncology Group Performance Status of 0-2 and histological diagnosis of chronic lymphocytic leukemia/small lymphocytic leukemia, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, acute lymphoid leukemia, acute myeloid leukemia, or non-Hodgkin lymphoma (NHL; mantle cell lymphoma [MCL], follicular lymphoma, marginal zone lymphoma, diffuse large B-cell lymphoma [DLBCL], Richter transformation, Burkitt lymphoma, and T-cell-NHL) were enrolled. Participants received zilovertamab vedotin intravenously at starting doses of 0.50 mg/kg (up to 2.5 mg/kg) on day 1 every 3 weeks (Q3W) (Schedule 1), 1.0 mg/kg (planned up to 2.25 mg/kg) on day 1 and 8 Q3W (Schedule 2), or 1.0 mg/kg (planned up to 2.25 mg/kg) on days 1, 8, and 15 Q4W (Schedule 3) using an accelerated plus 3+3 dose escalation design. The primary end point was determination of the maximum tolerated dose (MTD). Secondary end points included safety, objective response rate (ORR), and duration of response (DOR). We present data for participants with NHL enrolled in Schedule 1. Results: A total of 51 patients were enrolled in Schedule 1 (starting dose 0.5 [n=1], 1.00 [n=3], 1.50 [n=3], 2.00 [n=3], 2.25 [n=11], or 2.50 [n=30] mg/kg) as of the data cutoff of May 18, 2021. Median (range) age of patients was 70 (44-91) years, 54.9% of patients were male, 49.0% had an ECOG PS of 0, and 41/51 (80%) were diagnosed with NHL; 13/51 (25.5%) were diagnosed with DLBCL and 17/51 (33.3%) were diagnosed with MCL. Enrollment in Schedules 2 and 3 is currently ongoing. The MTD for Schedule 1 was determined to be 2.5 mg/kg. Any-cause adverse events (AEs) occurred in 48 patients (94.1%), most commonly (≥30%) nausea (45.1%), fatigue (45.1%), peripheral neuropathy (41.2%), diarrhea (37.3%), dizziness (35.3%), and neutrophil count decrease (33.3%). Grade ≥3 AEs occurred in 33 (64.7%) patients, most commonly (≥5%) neutrophil count decrease (29.4%), hemoglobin decrease (15.7%), febrile neutropenia (7.8%), peripheral neuropathy (7.8%), platelet count decrease (7.8%), diarrhea (5.9%), lipase increase (5.9%), and pneumonia (5.9%). One patient died due to acute respiratory failure; however, it was not considered treatment-related by the investigator. A total of 7 (13.7%) patients permanently discontinued due to an AE and 18 (35.3%) had treatment interrupted or reduced due to an AE. Treatment-related AEs occurred in 36 patients (70.6%), most commonly (≥20%) peripheral neuropathy (41.2%), fatigue (37.3%), neutrophil count decrease (29.4%), nausea (27.5%), and diarrhea (21.6%); 24 patients (47.1%) experienced a grade ≥3 treatment-related AE. For Schedule 1, ORR was 36.6% (15/41 [95% CI: 22.1%-53.1%]) among all participants with NHL, with 5 having a complete response (CR) and 10 having a partial response (PR). ORR was 38.5% (95% CI: 13.9%-68.4%) for the 13 patients in the NHL group who had DLBCL; 3 patients had a CR and 2 patients had a PR. ORR was 52.9% (95% CI: 27.8%-77.0%) for the 17 patients in the NHL group who had MCL; 2 patients had a CR and 7 patients had a PR. Median (range) DOR was 7.8 months (2.1-17.6+ months) among all participants in Schedule 1 with NHL who achieved a response. Conclusion: These data suggest that targeting the ROR1 pathway with zilovertamab vedotin is associated with a tolerable safety profile and promising antitumor activity in patients with relapsed/refractory NHL. Disclosures Wang: Anticancer Association: Honoraria; Dava Oncology: Honoraria; BioInvent: Research Funding; Bayer Healthcare: Consultancy; Hebei Cancer Prevention Federation: Honoraria; Lilly: Research Funding; Scripps: Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Research Funding; CAHON: Honoraria; InnoCare: Consultancy, Research Funding; Molecular Templates: Research Funding; Pharmacyclics: Consultancy, Research Funding; Oncternal: Consultancy, Research Funding; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Genentech: Consultancy; Newbridge Pharmaceuticals: Honoraria; VelosBio: Consultancy, Research Funding; Celgene: Research Funding; Physicians Education Resources (PER): Honoraria; The First Afflicted Hospital of Zhejiang University: Honoraria; OMI: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Loxo Oncology: Consultancy, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; Chinese Medical Association: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Clinical Care Options: Honoraria; Mumbai Hematology Group: Honoraria; Moffit Cancer Center: Honoraria; BGICS: Honoraria; CStone: Consultancy; Imedex: Honoraria; Epizyme: Consultancy, Honoraria; Acerta Pharma: Consultancy, Honoraria, Research Funding. Mei: Janssen: Honoraria; EUSA: Honoraria; Sanofi-Genzyme: Honoraria; Morphosys: Honoraria; TG Therapeutics: Other: Institution: Research Grant/Funding; Epizyme: Other: Institution: Research Grant/Funding; BMS: Other: Institution: Research Grant/Funding; Beigene: Other: Institution: Research Grant/Funding; Incyte: Other: Institution: Research Grant/Funding. Barr: Beigene: Consultancy; Gilead: Consultancy; Morphosys: Consultancy; TG Therapeutics: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy; Janssen: Consultancy; Abbvie/Pharmacyclics: Consultancy; Bristol Meyers Squibb: Consultancy; Seattle Genetics: Consultancy. Furman: Acerta/AstraZeneca: Consultancy; Janssen: Consultancy, Honoraria; Beigene: Consultancy; Genentech: Consultancy; Incyte: Consultancy; Loxo Oncology: Consultancy; Abbvie: Consultancy, Honoraria, Other: Expert testimony; AstraZeneca: Honoraria; Sunesis: Consultancy; Oncotracker: Consultancy; Pharmacyclics: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy; Morphosys: Consultancy; Sanofi: Consultancy; X4 Pharmaceuticals: Consultancy. Patel: TG Therapeutics: Consultancy, Speakers Bureau; Abbvie: Consultancy; Sunesis Pharmaceuticals: Research Funding; Juno Pharmaceuticals: Consultancy; MEI Pharma: Consultancy, Research Funding; Kite: Consultancy, Research Funding, Speakers Bureau; Millenium/Takeda: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding, Speakers Bureau; Morphosys: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau; Trillium Therapeutics: Research Funding; BeiGene: Consultancy; Aptevo Therapeutics: Research Funding; Fate Therapeutics: Research Funding; Xencor: Research Funding; Velos Bio: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Curis, Inc: Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau. Thompson: AbbVie: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding; Genentech: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding; Adaptive Biotechnologies: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding, Expert Testimony; Pharmacyclics: Other: Institution: Advisory/Consultancy, Honoraria, Research Grant/Funding; Janssen: Consultancy, Honoraria; Gilead: Other: Institution: Advisory/Consultancy, Honoraria; Amgen: Other: Institution: Honoraria, Research Grant/Funding. Choi: Abbvie: Other: Institution: Research Grant/Funding; Pharmacyclics: Other: Institution: Research Grant/Funding; Oncternal: Other: Institution: Research Grant/Funding; Velosbio: Other: Institution: Research Grant/Funding; Merck: Other: Institution: Research Grant/Funding; Geron: Other: Institution: Research Grant/Funding. Zhu: Merck & Co., Inc.: Current Employment. Chakraborty: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Spurgeon: Ionis: Other: Institution: Research Grant/Funding; Gilead Sciences: Other: Institution: Research Grant/Funding; Bristol Myers Squibb: Other: Institution: Research Grant/Funding; BeiGene: Other: Institution: Research Grant/Funding; AstraZeneca: Other: Institution: Research Grant/Funding; Acerta Pharma: Other: Institution: Research Grant/Funding; Pharmacyclics: Consultancy; Janssen: Consultancy, Other: Institution: Research Grant/Funding; Genentech: Consultancy, Other: Institution: Research Grant/Funding; Karyopharm: Consultancy; Velos Bio: Consultancy, Other: Institution: Research Grant/Funding; Merck & Co., Inc.: Other: Institution: Research Grant/Funding; Fred Hutchinson Cancer Research Center: Other: Data Safety Monitoring Board.

Introduction: The open-label, international, randomized, phase 3 KEYNOTE-204 (NCT02684292) study showed that in pts with R/R cHL, the PD-1 inhibitor pembro was superior to BV and demonstrated statistically significant, clinically meaningful improvement in PFS, with safety consistent with previous reports. This post hoc exploratory analysis of KEYNOTE-204 evaluated pembro vs BV by number of prior lines of therapy. Methods: Eligible pts were aged ≥18 y, had measurable disease and ECOG PS 0 or 1, and were post−autologous stem cell transplant (auto-SCT) or ineligible for auto-SCT. Pts who were BV-naive or BV-exposed were also eligible. Pts were randomized 1:1 to pembro 200 mg IV Q3W or BV 1.8 mg/kg IV Q3W. Randomization was stratified by status after 1L therapy (primary refractory vs relapsed Results: Of 304 randomized pts, 55 (pembro, 27; BV, 28) received 1 prior therapy and 249 (pembro, 124; BV, 125) received ≥2 prior therapies. For pts with 1 prior therapy, median (range) age was 49 y (22-84) and 22 pts (40.0%) were aged ≥65 y. No pts received prior auto-SCT and 18 (32.7%) had primary refractory disease. Auto-SCT ineligibility was due to chemorefractory disease for 21 pts (38.2%) and reasons not related to chemorefractory disease (eg, age, comorbidities) for 34 pts (61.8%). 23 pts (85.2%) and 25 pts (92.6%) in the pembro and BV groups, respectively, discontinued treatment; the most common reason was progressive disease. Median (range) time from randomization to data cutoff was 24.0 mo (18.7-34.8) for pembro and 23.6 mo (18.2-34.6) for BV. For the primary PFS analysis, median PFS was 16.4 mo for pembro and 8.4 mo for BV (HR 0.70; 95% CI 0.031-1.59); 12 mo PFS rates were 58.9% and 37.4%, respectively. For the secondary PFS analysis, median PFS was 11.7 mo for pembro and 8.3 mo for BV (HR 0.62; 95% CI 0.28-1.40). ORR was 66.7% for pembro and 53.6% for BV. Median (range) DOR for pembro was 20.7 mo (2.8-20.7) and 14.1 mo (0.0+ to 21.9) for BV. 7 pts (25.9%) and 9 pts (33.3%) in the pembro and BV groups, respectively, received subsequent auto-SCT; 1 pt in the BV group received subsequent allo-SCT. 21 pts (77.8%) on pembro and 20 (74.1%) on BV experienced a treatment-related adverse event (TRAE); most common were hyperthyroidism (22.2%) for pembro and peripheral neuropathy (22.2%) for BV. 1 (3.7%) and 8 (29.6%) of pts on pembro and BV, respectively, experienced grade 3-5 TRAEs. For pts with ≥2 prior therapies median (range) age was 34 y (18-83) and 27 (10.8%) pts were aged ≥65 y. 112 pts (45.0%) received prior auto-SCT and 105 (42.2%) had primary refractory disease. Median (range) time from randomization to data cutoff was 27.1 mo (18.8-42.0) for pembro and 27.6 (18.2-42.3) for BV. 87 (71.9%) and 121 (96.8%) in the pembro and BV groups discontinued; most common reason was progressive disease. For the primary PFS analysis, median PFS was 12.6 mo for pembro and 8.2 mo for BV (HR 0.66; 95% CI 0.47-0.92); 12-mo PFS rates were 52.8% and 35.3%, respectively. For the secondary PFS analysis, median PFS was 12.6 mo for pembro and 8.2 mo for BV (HR 0.63; 95% CI 0.45-0.88). ORR for pembro was 65.3% and 54.4% for BV. Median (range) DOR for pembro was 20.5 mo (0.0+ to 33.2+) and 11.2 mo (0.0+ to 33.9+) for BV. 23 (19.0%) and 25 (20.0%) pts in the pembro and BV groups, respectively, received subsequent auto-SCT; 14 (11.6 %) and 12 (9.6%) received subsequent allo-SCT. 89 pts (73.6%) on pembro and 97 (77.6%) on BV experienced a TRAE; most common were hypothyroidism (14.9%) for pembro and peripheral neuropathy (17.6%) for BV. 23.1% and 24.0% of pts on pembro and BV, respectively, experienced grade 3-5 TRAEs. Conclusion: In pts with R/R cHL, pembro monotherapy resulted in an improvement in PFS and ORR vs BV in pts regardless of number of prior therapies. In particular, these data suggest that pembro monotherapy may be a promising option as 2L+ therapy for pts with R/R cHL ineligible for auto-SCT. Disclosures Kuruvilla: Bristol-Myers Squibb Company: Consultancy; TG Therapeutics: Honoraria; Pfizer: Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy; Karyopharm: Consultancy, Honoraria; AstraZeneca Pharmaceuticals LP: Honoraria, Research Funding; Novartis: Honoraria; Antengene: Honoraria; Merck: Consultancy, Honoraria; Celgene Corporation: Honoraria; Amgen: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria. Ramchandren:Seattle Genetics, Sandoz-Novartis, Pharmacyclics, an AbbVie Company, Janssen, Bristol-Myers Squibb: Consultancy; Merck, Seattle Genetics, Janssen, Genentech: Research Funding. Santoro:Arqule, Sanofi: Consultancy; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau. Paszkiewicz-Kozik:Roche, Takeda, Celgene: Other: Travel, accommodations, expenses. Gasiorowski:MSD, Takeda, Novartis, AbbVie: Honoraria. Johnson:Roche/Genentech, Merck: Honoraria; Roche/Genentech, Merck, Bristol-Myers Squibb, AbbVie: Consultancy; AbbVie: Research Funding. Goncalves:Janssen, Takeda, Amgen, Bayer, Novartis, Merck, Bayer, Celgene, GSK, BMS: Research Funding; Janssen: Consultancy, Speakers Bureau. Perini:Janssen, Takeda: Honoraria; AbbVie, Janssen: Speakers Bureau. Goldschmidt:Abbvie Inc: Consultancy, Research Funding. Kryachok:Janssen, Bayer, Karyopharm, MSD, AbbVie, Acerta, Debiopharm: Research Funding; Takeda, Janssen: Consultancy; Takeda, MSD, AbbVie, Roche: Other: Travel, accommodations, expenses. Sekiguchi:Ono, A2 Healthcare, Astellas, Janssen, Merck Sharp & Dohme, Otsuka, Pfizer, PPD-SNBL, Sumitomo Dainippon, Daiichi Sankyo, and Bristol-Myers Squibb: Research Funding. Lin:Merck & Co., Inc.: Current Employment. Nahar:Merck Sharp & Dohme, Corp., a subsididary of Merck & Co., Inc., Kenlworth, NJ, USA: Current Employment. Marinello:Merck & Co., Inc.: Other: Travel, accommodations, expenses; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Current Employment; Merck & Co., Inc., Kenilworth, NJ, USA: Other: Stock ownership. Zinzani:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction: Standard of care for patients (pts) with relapsed or refractory classic Hodgkin lymphoma (R/R cHL) remains salvage chemotherapy with subsequent autologous stem cell transplantation (ASCT), which leads to long-term remission in about half of pts. Prognosis is poor for pts who relapse or progress after ASCT, particularly among pts who relapse after prior treatment with brentuximab vedotin (BV). Programmed death 1 (PD-1) inhibitors are an effective therapeutic option. Previous analyses of the multicohort phase 2 KEYNOTE-087 (NCT02453594) study showed that PD-1 pathway inhibition with pembrolizumab (pembro) led to effective antitumor activity and acceptable safety in pts with R/R cHL. KEYNOTE-087 results led to FDA approval of pembro for adult and pediatric pts with R/R cHL who relapsed after ≥3 prior lines of therapy. Long-term durability of response is a key clinical question for pts receiving immunotherapy. We present efficacy and safety of patients in KEYNOTE-087 who received 3 y of follow-up and evaluate antitumor activity in pts who were re-treated after disease progression. Methods: Pts with R/R cHL who progressed after ASCT and subsequent BV therapy (cohort 1), underwent salvage chemotherapy and BV and were ineligible for ASCT (cohort 2), or progressed after ASCT but were not treated with BV after ASCT (cohort 3) were enrolled and received pembro 200 mg IV Q3W. Pts who discontinued pembro after initial confirmed CR after ≥6 mo of treatment and then experienced disease progression were eligible to receive an additional ≤17 cycles (~1 y) of pembro (second course). Response was assessed Q12W per 2007 Revised Response Criteria for Malignant Lymphomas. Primary end points were safety and overall response rate (ORR) per blinded independent central review in all pts in each cohort. Secondary end points included complete remission (CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results : At data cutoff, median follow-up was 39.5 mo (range, 1.0-44.8). In the total population (N=210), 46 pts completed 2 y of treatment, 164 pts discontinued (primary reason, progressive disease [n=86]). ORR was 71.0% (95% CI, 64.3-77.0) with 58 CRs (27.6%) and 91 PRs (43.3%). ORR was 78.3% (CR, n=18; PR, n=36) in cohort 1 (n=69), 64.2% (CR, n=21; PR, n=31) in cohort 2 (n=81), and 71.7% (CR, n=19; PR, n=24) in cohort 3 (n=60). Overall median DOR was 16.6 mo (95% CI, 0.0+ to 39.1+). 45.1% of pts had a response duration ≥24 mo; 26.9% had a response duration ≥36 mo. 19/149 (12.8%) pts had an ongoing response. Median DOR was 25.0 mo in cohort 1, 11.1 mo in cohort 2, and 16.8 mo in cohort 3. In the total population, median PFS was 13.6 mo (95% CI, 11.1-16.7) and the 36-mo PFS rate was 18.8%. Median PFS was 16.4 mo (95% CI, 11.3-27.6) in cohort 1, 11.1 mo (95% CI, 7.3-13.5) in cohort 2, and 19.4 mo (95% CI, 8.4-22.1) in cohort 3. Median OS was not reached in the total population or in the cohorts; 36-mo OS rate was 86.4% in the total population, 86.3% in cohort 1, 85.7% in cohort 2, and 87.6% in cohort 3. 17 pts entered the second-course phase, of whom 16 were evaluable for response (8 in cohort 1, 6 in cohort 2, 2 in cohort 3). 4 pts completed 17 cycles of treatment; 7 pts have ongoing treatment. Second-course ORR was 68.8% with 5 CRs (31.3%) and 6 PRs (37.5%); 4 pts (25.0%) had stable disease. ORR for cohorts 1, 2, and 3 was 75.0% (CR, n=1; PR, n=5), 83.3% (CR, n=4; PR, n=1), and 0.0%, respectively. Both pts in cohort 3 had stable disease; 1 completed 17 cycles of pembro and the other is still receiving treatment. Treatment-related adverse events (AEs) of any grade occurred in 72.9% of pts; the most commonly reported were hypothyroidism (14.3%), pyrexia (11.4%), fatigue (11.0%), and rash (11.0%). Grade 3-4 treatment-related AEs occurred in 11.9% of pts; only neutropenia (n=5) and diarrhea (n=2) occurred in ≥2 pts. No grade 5 treatment-related AEs occurred. Conclusions: With a median of 39.5 mo of follow-up, pembro continued to demonstrate clinically important antitumor activity in pts with R/R cHL. In the total population and in pts with different treatment histories, ORRs were high and responses were durable. Second-course pembro was able to re-induce remission in most patients who previously reached CR. Safety was manageable, and no unexpected AEs occurred. Disclosures Zinzani: VERASTEM: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; IMMUNE DESIGN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PORTOLA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANOFI: Consultancy. Armand:Sigma-Tau: Research Funding; Otsuka: Research Funding; Pfizer Inc: Research Funding; Merck & Co.: Employment, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; Affimed: Research Funding; Serventa: Research Funding; Bristol Myers Squibb Pharmaceuticals: Employment, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; Infinity Pharmaceuticals: Employment, Membership on an entity's Board of Directors or advisory committees; Dana-Farber Cancer Institute: Employment; Roche: Research Funding. Johnson:Lundbeck: Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; BD Biosciences: Other: Provided a significant proportion of the antibodies used in this project free of cost.; Seattle Genetics: Honoraria; BMS: Consultancy, Honoraria; Roche: Consultancy, Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; Abbvie: Consultancy, Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria. Brice:Millennium Takeda: Research Funding; BMS: Honoraria; Takeda France: Consultancy, Honoraria. Radford:Novartis: Consultancy, Honoraria; GSK: Equity Ownership; BMS: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; AstraZeneca: Equity Ownership, Research Funding. Ribrag:Incyte: Membership on an entity's Board of Directors or advisory committees; AZ: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses ; Infinity: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; ArgenX: Research Funding; Epizyme: Consultancy, Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel, accommodations, and expenses . Molin:Merck & Co., Inc.: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria; Roche Holding AG: Honoraria. Vassilakopoulos:Takeda Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others; Genesis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Tomita:Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Kyowa Kirin: Research Funding; Taiho Pharma: Research Funding. Von Tresckow:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; Takeda Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; Amgen: Honoraria; Celgene: Honoraria; Merck Sharp & Dohme Corp: Research Funding. Shipp:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; Merck & Co.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees. Herrera:Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Gilead Sciences: Consultancy, Research Funding. Lin:Merck & Co., Inc.: Employment. Kim:Merck & Co., Inc.: Employment, Other: Stock or other ownership. Farooqui:Merck & Co., Inc.: Employment, Other: Stock or Other Ownership. Marinello:Merck & Co., Inc.: Employment, Other: Travel fees, gifts, and others; stock or other ownership. Moskowitz:Genentech: Consultancy, Research Funding; Celgene: Consultancy; Pharmacyclics: Research Funding; ADC Therapeutics: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Merck: Consultancy, Research Funding.

Background: The prognosis is poor for most patients with lymphoma who do not respond to initial therapy, leaving an unmet need for effective therapies for this patient population. Pembrolizumab, a programmed death 1 (PD-1) inhibitor, has shown clinically meaningful antitumor activity and manageable safety in multiple tumor types, including relapsed or refractory (R/R) classic Hodgkin lymphoma (R/R cHL) and R/R primary mediastinal large B-cell lymphoma. Results of preclinical studies have shown that lymphocyte activation gene-3 (LAG-3), a cell surface immunomodulatory receptor protein, is elevated in hematologic malignancies and that blockade of LAG-3 and the PD-1/PD ligand 1 (PD-L1) axis has synergistic antitumor activity in solid tumors. MK-4280 is a humanized anti-LAG-3 monoclonal antibody that blocks the interaction between LAG-3 and its ligand. The current study will evaluate the safety and efficacy of pembrolizumab combined with MK-4280 in patients with selected hematologic malignancies. Study Design and Methods: This phase 1-2 multisite, multicohort, open-label study (NCT03598608) will have a safety lead-in phase to establish the preliminary recommended phase 2 dose (RP2D) followed by an efficacy expansion phase. In the safety lead-in phase, a modified toxicity probability interval design will be used to establish the RP2D of pembrolizumab plus MK-4280. Dose-limiting toxicities will be assessed during the first cycle. The study will enroll patients with PD-1/PD-L1 inhibitor-naive R/R cHL (cohort 1), PD-1/PD-L1 inhibitor-refractory R/R cHL (cohort 2), R/R diffuse large B-cell lymphoma (cohort 3), and R/R indolent non-Hodgkin lymphoma (cohort 4). Adult patients (age ≥18 years) with ECOG PS 0 or 1 and adequate organ function who meet the standard eligibility criteria for pembrolizumab studies, such as no prior receipt of anti-PD-1 antibody and no active infection necessitating systemic therapy, will be enrolled. Patients will receive pembrolizumab 200 mg every 3 weeks and MK-4280 for 35 cycles (~2 years) or until documented disease progression, unacceptable toxicity, intercurrent illness preventing further administration of study drug, or withdrawal from study. Tumor response will be assessed by computed tomography/positron emission tomography every 12 weeks to confirm complete response or as clinically indicated, using revised response criteria for malignant lymphoma. Patients will be monitored for adverse events (AEs) until 30 days after study treatment end (90 days for serious AEs). After confirmed disease progression or start of new anticancer therapy, patients will be contacted by telephone every 12 weeks for survival status. All-patients-as-treated (APaT), defined as all patients who received ≥1 dose of the study drug, will constitute the safety population. The full analysis set, defined as all patients with a baseline assessment who have measurable disease by investigator assessment and who were administered a dose of study intervention, regardless of dose level, will constitute the efficacy population. The primary objective is to determine the safety and tolerability of MK-4280 plus pembrolizumab and establish its RP2D. Secondary objectives are to evaluate the objective response rate of MK-4280 when combined with pembrolizumab per investigator assessment and to evaluate the pharmacokinetics of MK-4280 and pembrolizumab. Exploratory objectives are to evaluate overall survival, progression-free survival, and best overall response for MK-4280 and pembrolizumab; to assess the presence of circulating MK-4280 and anti-pembrolizumab antibodies; to assess target engagement and pharmacodynamics of MK-4280 through biomarker evaluation; and to identify molecular biomarkers associated with clinical response/resistance, safety, pharmacodynamics, and/or the mechanism of action of MK-4280 and pembrolizumab. At least 14 patients (≥3 per cohort) will be enrolled in the safety lead-in phase; approximately 120 patients (≤30 per cohort) will be enrolled in the efficacy expansion phase. Disclosures Armand: Serventa: Research Funding; Sigma-Tau: Research Funding; Otsuka: Research Funding; Merck & Co.: Employment, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; Roche: Research Funding; Pfizer Inc: Research Funding; Affimed: Research Funding; Bristol Myers Squibb Pharmaceuticals: Employment, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; Infinity Pharmaceuticals: Employment, Membership on an entity's Board of Directors or advisory committees; Dana-Farber Cancer Institute: Employment. Zinzani:PORTOLA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; SANOFI: Consultancy; CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; IMMUNE DESIGN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; VERASTEM: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Palcza:Merck & Co., Inc.: Employment, Other: Stock ownership. Healy:Merck & Co., Inc.: Employment, Other: Stock ownership. Nahar:Merck & Co., Inc.: Employment. Marinello:Merck & Co., Inc.: Employment, Other: Travel fees, gifts, and others; stock or other ownership. Gregory:Gilead: Membership on an entity's Board of Directors or advisory committees; AbbVie: Other: grant pending, Research Funding; Monash University: Research Funding; Janssen: Other: grant pending, Research Funding; Roche: Speakers Bureau; Beigene: Other: Grant pending, Research Funding; Melbourne Haematology: Consultancy, Honoraria, Other: Travel fees and conference support, Speakers Bureau; Celgene: Other: grant pending, Research Funding; MSD: Other: grant pending, Research Funding.

Introduction: Currently available therapy options for primary mediastinal large B-cell lymphoma (PMBCL) generally yield poor treatment outcomes. Like classical Hodgkin lymphoma (cHL), PMBCL frequently exhibits 9p24.1/PD-L1/PD-L2 copy number alterations and rearrangements and associated PD-L1 and/or PD-L2 overexpression, which may facilitate immune evasion. The genetics of PMBCL could thus make it susceptible to PD-1 blockade. KEYNOTE-013 (NCT01953692) is an ongoing multicenter, multicohort Phase 1b trial evaluating safety, tolerability, and antitumor activity of pembrolizumab, a humanized anti-PD-1 monoclonal antibody, in patients with hematologic malignancies. Here we report results from the first 19 patients enrolled in the PMBCL cohort of KEYNOTE-013, with a follow-up of up to 2 years. Methods: This independent cohort of KEYNOTE-013 is enrolling patients with relapsed/refractory (R/R) PMBCL who have relapsed after or are ineligible for autologous stem cell transplant (SCT). Patients received pembrolizumab IV 10 mg/kg every 2 weeks (Q2W), which was later changed by protocol amendment to a fixed dose of 200 mg every 3 weeks (Q3W), following PK/PD studies demonstrating both regimens to be equivalent. Treatment continues for up to 2 years or until unacceptable toxicity or confirmed disease progression. Treatment response is evaluated using IHP 2007 criteria by positron emission tomography and computed tomography at weeks 6 and 12, and every 9 weeks thereafter. Primary end points are safety and objective response rate (ORR). Secondary end points include complete remission (CR) rate and duration of response (DOR). The safety population consists of all patients who receive ≥1 dose of study drug and the efficacy population of all patients who progress prior to or reach the first efficacy evaluation. Whole blood was collected at predefined time points before and during pembrolizumab treatment for RNA and DNA extraction and biomarker analysis using a number of genomic-based assays, including NanoString and RNA sequencing. Results: As of the analysis cutoff date (May 27, 2016), 19 patients were enrolled in the PMBCL cohort, 18 were treated, and 16 had ≥1 post-baseline efficacy evaluation. The first 11 patients were to receive pembrolizumab IV 10 mg/kg Q2W (1 was not treated due to early progressive disease); all subsequent patients received 200 mg Q3W. Median age was 30.5 years (range, 22-62). Most patients (72%) were female. 61% of patients had ≥3 prior lines of therapy, 33% had prior autologous SCT, and 61% prior radiation. In the efficacy population, 16 patients were evaluable for response: one discontinued treatment based on clinical progression before the first response assessment (this patient was considered a nonresponder), the other had not reached the first assessment.The ORR was 41% (7/17), with 2 patients achieving a CR and 5 patients a partial response; 35% (6/17) had stable disease as best response. Overall, 81% (13/16) of evaluable patients had target lesion reductions (Figure). With a median follow-up duration of 11.3 months (range, 3.4 to 27.4 months), median DOR was not reached, and there were 6 ongoing responses at time of current data cutoff. DOR ranged from 2.4+ to 22.5+ months; DOR in the 2 patients with CR was 2.4+ and 20.5+ months. Two patients received an allogeneic SCT: one had SD, the other PD on pembrolizumab. Ten patients discontinued treatment: 5 due to progressive disease based on imaging, 4 for clinical progression, and 1 due to physician decision. Two patients reached the maximum 2 years of treatment and remain in remission. Six patients experienced serious AEs, and none discontinued due to AEs. Eleven patients (61%) experienced treatment-related adverse events (TRAEs), mostly grade 1-2. One patient experienced a TRAE of grade 3 neutropenia and another a TRAE of grade 4 venoocclusive liver disease (VOD; after allogeneic SCT during the follow-up period after pembrolizumab was discontinued), the only serious TRAE. The patient recovered from the VOD. There were no treatment-related deaths. Conclusions: These results from an on-going study in heavily pretreated R/R PMBCL patients demonstrate that PD-1 blockade with pembrolizumab has a manageable safety profile and promising antitumor activity. Due to these results, a pivotal global multi-center Phase 2 trial, KEYNOTE-170, is further evaluating single agent pembrolizumab in patients with R/R PMBCL. Figure. Figure. Disclosures Zinzani: MorphoSys: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Ribrag:Esai: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; ArgenX: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; NanoString: Membership on an entity's Board of Directors or advisory committees. Moskowitz:Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck & Co., Inc.: Consultancy, Research Funding; Celgene Corporation: Consultancy; Genentech BioOncology: Consultancy. Michot:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Kuruvilla:Merck & Co., Inc.: Consultancy, Honoraria. Balakumaran:Merck & Co.: Employment, Other: stock, stock options. Zhang:Merck & Co., Inc.: Employment, Other: stock, stock options. Marinello:Merck & Co., Inc.: Employment, Other: stock, stock options. Chlosta:Merck & Co., Inc.: Employment, Other: stock, stock options. Gustafson:Merck & Co., Inc.: Employment, Other: stock, stock options. Shipp:Merck & Co., Inc.: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding. Armand:Otsuka: Research Funding; Merck & Co., Inc.: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Infinity: Consultancy; Roche: Research Funding; Sequenta: Research Funding; Tensha: Research Funding; Sigma Tau: Research Funding.

Background: Carfilzomib (Car, 2012), pomalidomide (Pom, 2013), and panobinostat (Pano, 2015) were approved for the treatment of rrMM patients after failure of at least two prior standard therapies. There is limited real-world data on utilization of these medications, health care resource utilization (HCRU) and costs in patients with rrMM at the US population level. This study aimed to describe treatment pattern, HCRU, and costs in rrMM patients who received at least two prior therapies using a large administrative claims database. Methods: This was a retrospective database analysis using the Truven Health MarketScan Commercial and Medicare Database. Patients (pts) were included if they were diagnosed with MM between Jan 1, 2006 and May 31, 2015, were ≥18 yrs, had no claim for stem cell transplant, and had ≥6 mos continuous enrollment before and ≥1 mos after the 1st MM diagnosis (index date) and treatment initiation (TI). Only patients who had ≥6 mos continuous enrollment after TI were included in HCRU and cost evaluation. If two or more drugs started within 90 days, they were considered as 1 regimen. End of a line of therapy (LOT) was defined when a new treatment was introduced or there was a treatment gap >90 days or end of follow-up, whichever occurred first. Third line of therapy (3L) was identified following 2 prior lines of therapy. Time to next treatment (TTNT) was defined from initiation of the LOT to initiation of subsequent LOT. Duration of treatment (DOT) and TTNT were estimated based on Kaplan-Meier method. Regimens were classified into 6 mutually-exclusive categories, including bortezomib (Bor), lenalidomide (Len), Pom, Car, thalidomide (Thal), and Other based therapies. HCRU and cost (per patient per month, PPPM) were calculated. The total costs included inpatient costs, outpatient costs and pharmacy costs. Results: A total of 9,960 pts were identified with initiation of 1L therapy. Median age was 67 yrs. And 57.4% were male. During an average of 20.0 mos follow-up post TI, 3,282 (33.0%), 1,103 (11.1%) and 400 (4%) pts initiated 2L, 3L, and 4L therapies, respectively. During 3L therapy, Bor (43.5%, including 10.5% for Bor-Len) and Len based regimens (29.8%) were most commonly observed. Median DOTs ranged from Car (3.7 mos) to Len (8.1 mos) based regimens. Median TTNT from short to long was Car, Pom, Bor, Len, Other, and Thal based regimens. On average, each patient with rrMM had 4.5 outpatient visits, 0.1 inpatients visits, 0.1 ER visits and 0.004 hospice care visits per month. The average PPPM costs were $14,286, $13,377, $11,919, for Bor, Len, Thal based regimens and $25,850 and $21,180 for Pom and Car based regimens, respectively. Conclusions: Although novel agents were added to rrMM treatment, Bor and/or Len based regimens remained the most commonly used therapies in 3L setting. Compared to Bor, Len and Thal based therapies, PPPM costs were higher for Pom and Car based regimens. These data could be useful for treatment consideration and economic evaluation. Table Table. Disclosures Shao: Merck & Co., Inc.: Employment. Monberg:Merck & Co.: Employment. Cao:Merck & Co.: Employment. Zhou:Merck & Co.: Employment. Zhong:Merck & Co., Inc.: Employment. Marinello:Merck & Co., Inc.: Employment.

Background: Overexpression of PD-L1 is associated with tumor invasiveness in multiple myeloma (MM) cells and may be a mechanism of immune evasion. Pembrolizumab, a highly selective, humanized IgG4 anti-PD-1 monoclonal antibody designed to block interaction of PD-1 with PD-L1 and PD-L2, may synergize with immunomodulatory drugs (IMiDs) to enhance tumor suppression. KEYNOTE-023 (NCT02036502), an open-label, phase 1, multicenter, nonrandomized, dose-escalation trial evaluated the safety, tolerability, and efficacy of pembrolizumab in combination with lenalidomide and low-dose dexamethasone in patients with RRMM. Methods: Patients with RRMM who have failed ≥2 prior therapies including a proteasome inhibitor and an IMiD were enrolled in the study. KEYNOTE-023 uses a modified 3+3 design for dose determination followed by dose confirmation and expansion arms. During the dose determination phase, cohorts of 3-6 patients were enrolled at 2 mg/kg of pembrolizumab every 2 weeks (Q2W) in combination with 10 mg or 25 mg of lenalidomide on days 1-21 and 40 mg low-dose dexamethasone weekly, to be repeated every 28 days. After preliminary MTD/MAD was identified, additional patients were to be enrolled at a fixed dose of 200 mg of pembrolizumab in combination with lenalidomide and dexamethasone in the dose confirmation and expansion arms. Study treatment is to continue for 24 months or until confirmed disease progression or unacceptable toxicity. The primary end points are safety and antitumor activity. Response is evaluated monthly, using IMWG 2006 criteria. Other end points include complete remission (CR) rate, duration of response (DOR), and exploratory biomarker analyses. Results: As of July 2015, a total of 34 patients with RRMM have been enrolled in the study. Data from 17 patients included in the dose determination and dose confirmation phase are presented in this abstract. All available data for patients currently enrolled in the study will be presented at the upcoming meeting. In the dose determination and dose confirmation phase, 4 patients were treated with pembrolizumab 2 mg/kg and lenalidomide 10 mg and 13 patients were treated with pembrolizumab 2 mg/kg or a fixed dose of 200 mg and lenalidomide 25 mg. All patients were treated with low-dose dexamethasone. The median age was 60 (46-76) years, and 59% of patients had stage (ISS) III disease. Patients were heavily pretreated: 53% had ≥3 prior therapies, 41% had IMiDs-refractory disease, and 18% had double refractory disease. Sixteen patients (94%) experienced at least 1 adverse event (AE) of any grade related to study treatment and 10 patients (58%) experienced grade 3/4 treatment-related AEs. No death or treatment discontinuation for toxicity has been observed. The most frequent treatment-related AEs were: thrombocytopenia (47%), neutropenia (41%), fatigue (29%), and anemia, hyperglycemia, and muscle spasms (23% each). No DLTs were observed in the 10-mg lenalidomide cohort. In the 25-mg lenalidomide cohort, 3 patients (3/13) experienced a dose-limiting toxicity (DLT): neutropenia (grade 3 and grade 4), infectious pneumonia (grade 3), and tumor lysis syndrome (grade 3) with hyperuricemia (grade 4). All patients recovered from the DLTs without treatment discontinuation. Based upon these data the MTD/MAD was defined as pembrolizumab 200 mg fixed dose in combination with lenalidomide 25 mg and low-dose dexamethasone 40 mg. With a median follow-up of 287 days (48-476), 13/17 patients responded to treatment. The objective response rate (ORR) was 76%, with 4 patients achieving a very good partial response and 9 patients achieving a partial response. ORR has also been observed in patients with IMiDs-refractory and double refractory disease. Updated efficacy data, including DOR, will be presented. Conclusions: The preliminary results of KEYNOTE-023 indicate that PD-1 blockade with pembrolizumab in combination with lenalidomide and dexamethasone is associated with a tolerable safety profile and promising antimyeloma activity in heavily pretreated patients with RRMM. Disclosures San Miguel: Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees. Off Label Use: The PD-1 pathway is an important mechanism of immune evasion for many tumors. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction of PD-1 with its ligands PD-L1 and PD-L2 on the tumor cell surface and, based upon pembrolizumab's antitumor immune activity in several solid tumors, it may be an effective option for treating hematological malignancies.. Mateos:Onyx: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shah:Array: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Reece:BMS: Honoraria, Research Funding; Merck: Research Funding; Amgen: Consultancy, Honoraria; Novartis: Honoraria, Research Funding; Millennium: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Osuka: Honoraria, Research Funding. Ge:Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA: Employment, Equity Ownership. Balakumaran:Merck: Employment, Equity Ownership; Amgen: Equity Ownership. Marinello:Merck: Employment, Equity Ownership. Orlowski:Array Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acetylon Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Millennium Pharaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Research Funding; Biotheryx: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Siegel:Celgene Corporation: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Merck: Speakers Bureau.

Introduction: Like classical Hodgkin lymphoma (cHL), PMBCL frequently harbors genetic alterations of the 9p24.1 locus, leading to overexpression of the PD-1 ligands, PD-L1 and PD-L2. This provides a possible mechanism of immune evasion and suggests that PMBCL could have a genetically determined vulnerability to PD-1 blockade. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands. Pembrolizumab has already demonstrated robust antitumor activity in advanced solid tumors and in cHL. KEYNOTE-013 (NCT01953692) is a multicenter, multicohort phase 1b trial testing the safety and preliminary efficacy of pembrolizumab in patients with hematologic malignancies. Based on its genetics, PMBCL was included as an independent cohort in this trial. Here we report the preliminary results in this patient population. Methods: The PMBCL cohort of KEYNOTE-013 is enrolling patients with relapsed/refractory (R/R) disease who have relapsed after or are ineligible for autologous stem cell transplant (ASCT). Pembrolizumab is administered intravenously at a dose of 10 mg/kg every 2 weeks for up to 2 years or until confirmed disease progression or unacceptable toxicity. The primary end points are safety and antitumor activity. Response is being evaluated using computed tomography (CT) and positron emission tomography (PET) at week 12 and every 8 weeks thereafter, using IHP 2007 criteria. Other end points include complete remission (CR) rate, duration of response (DOR), and exploratory biomarker analyses. Results: As of July 23, 2015, 10 patients with R/R PMBCL with a median age of 28 (23-62) years have been enrolled in this cohort. Patients were heavily pretreated: 40% had ≥4 prior lines of therapy, and 60% had prior radiation. Six patients (60%) experienced at least 1 adverse event (AE) of any grade related to study treatment. These treatment-related AEs, all grade 1/2, were: hypothyroidism and decreased appetite (2 patients each), and diarrhea, nausea, vomiting, fatigue, edema, weight loss, and arthralgia (1 patient each). There were no grade 3-5 treatment-related AEs. Two patients experienced a serious AE (grade 3 infectious pneumonia) unrelated to study drug. No patient discontinued for toxicity. Nine patients were evaluable for response (1 discontinued treatment based on clinical progression before week 12). The objective response rate (ORR) was 44% (4/9), with 1 patient achieving a CR and 3 patients achieving a partial response. The intent-to-treat ORR was 40%. With a median follow-up of 144 days, the median DOR has not been reached (1+ to 291+) days, with all 4 responses ongoing at the time of data cutoff. Six of 10 patients have discontinued study treatment because of disease progression, and 4 patients remain on study. Conclusion: The preliminary results of KEYNOTE-013 indicate that PD-1 blockade with pembrolizumab is associated with a tolerable safety profile and a promising response rate in heavily pretreated patients with R/R PMBCL. Those patients often have a very poor outcome with conventional therapy, justifying further studies of pembrolizumab in this population. Disclosures Zinzani: Gilead: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Off Label Use: The PD-1 pathway is an important mechanism of immune evasion for many tumors. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction of PD-1 with its ligands PD-L1 and PD-L2 on the tumor cell surface and, based upon pembrolizumab's antitumor immune activity in several solid tumors, it may be an effective option for treating hematological malignancies.. Ribrag:Pharmamar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Esai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees. Moskowitz:Genentech: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Honoraria, Research Funding; Pharmacyclics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Kuruvilla:Merck: Honoraria; Bristol-Myers Squibb: Honoraria; Hoffmann LaRoche: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy; Karyopharm: Honoraria. Balakumaran:Merck: Employment, Equity Ownership; Amgen: Equity Ownership. Snyder:Merck: Employment, Equity Ownership. Marinello:Merck: Employment, Equity Ownership. Shipp:BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Armand:Infinity: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Sequenta, Inc.: Research Funding; BMS: Research Funding.