BackgroundAdenoid cystic carcinoma (ACC) is a rare tumor of secretory glands. In this study, recent advances in molecular characterization and in therapeutics are reviewed.MethodsA search of articles in PubMed and of abstracts from national meetings was performed regarding ACC.ResultsRecent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published that may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare.ConclusionACCs have a characteristic chromosomal translocation, but also frequently pick up additional mutations. Clinical research is limited by the rarity and slow growth of ACC. Several ongoing trials are testing agents that inhibit fibroblast growth factor receptor signaling or other signaling pathways. Novel treatments based on the recently sequenced tumor genome are under development. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. 38: 620–627, 2016

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.

Altered endometrial morphology and increased receptor levels in DUB patients suggest that unopposed estrogen effect could have an important role in the pathogenesis of DUB. Cases of DUB, which showed atypical hyperplasia, may have a down-regulation of these receptors and could be a precursor lesion to carcinoma and thus do not respond to medical therapy by hormones.

329 Background: Surgical therapy remains the only curative modality for pancreatic cancer, though survival remains quite poor even for patients with resected early stage disease. Better (neo) adjuvant therapies are needed to improve resectability rates for patients with borderline resectable pancreatic cancer and to prevent recurrence following resection. We undertook this pilot study to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in such patients. Methods: Eligible patients have histologically confirmed borderline resectable adenocarcinoma of the pancreas as defined by the MD Anderson categories of vascular involvement, indeterminate metastatic disease, borderline performance status; normal organ function; and no prior therapy for pancreatic cancer. Radiation is given as external beam radiation therapy to a dose of 50 Gy delivered in 20, 2.5 Gy fractions Mon-Fri using IMRT. If insurance denied IMRT, 3D conformal techniques with daily image guidance is permitted. Capecitabine is delivered as 825mg/m2 BID on radiation days. The primary outcome is to determine the frequency of treatment-related adverse events (AE). Planned enrollment is 40 pts. Results: 10 pts have enrolled to date. 8/10 received IMRT. This regimen has been exceedingly tolerable. Lymphopenia is the most common AE (n=10), grade 3-4 n=6. Other common toxicities were hyponatremia (n=6), fatigue (n=5). Grade 3 AE occurred in 8 pts, grade 4 in 3 patients. One pt had hemorrhage from a radiation induced gastric ulcer complicated by an MI. 5/10 pts had stable disease and were resected and 4/5 had an R0 resection. In the remaining 5/10 patients, disease progressed outside the pancreas and they are receiving palliative therapy. Conclusions: The combination of AFRT and capecitabine was well tolerated. Xenograft models derived from these patients’ tumors are being used to study molecular mechanisms of treatment resistance that could be targeted in a follow up phase II study building on this platform.

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: 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.

No abstract

No abstract