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Programmed cell death protein 1 (PD-1) and PD-ligand 1 (PD-L1) expression is upregulated in cluster of differentiation 34 (CD34)+ bone marrow cells from patients with myelodysplastic syndromes (MDS). Hypomethylating agent (HMA) treatment results in further increased expression of these immune checkpoints. We hypothesised that combining an anti-PD-1 antibody with HMAs may have efficacy in patients with MDS. To test this concept, we designed a phase II trial of the combination of azacitidine and pembrolizumab with two cohorts. In the 17 previously untreated patients, the overall response rate (ORR) was 76%, with a complete response (CR) rate of 18% and median overall survival (mOS) not reached after a median follow-up of 12·8 months. For the HMA-failure cohort (n = 20), the ORR was 25% and CR rate was 5%; with a median follow-up of 6·0 months, the mOS was 5·8 months. The most observed toxicities were pneumonia (32%), arthralgias (24%) and constipation (24%). Immune-related adverse events requiring corticosteroids were required in 43%. Overall, this phase II trial suggests that azacitidine and pembrolizumab is safe with manageable toxicities in patients with higher-risk MDS. This combined therapy may have anti-tumour activity in a subset of patients and merits further studies in the front-line setting.

Background: Hypomethylating agents (HMAs) are the standard of care in patients with higher-risk myelodysplastic syndrome (MDS). However, the expression of PD-1 and PD-L1 was found to be increased in CD34 positive cells from patients with MDS (Yang H, Leukemia 2014). Pembrolizumab is a humanized monoclonal antibody targeting PD-1, thus blocking its interaction with its ligands PD-L1 and PD-L2. A phase 1b, multicohort study of pembrolizumab in advanced hematologic malignancies revealed that a small number of patients with higher-risk MDS had long-term survival and no immune-mediated adverse events (Garcia-Manero G, Blood 2016). We report updated results from a phase II clinical trial evaluating the safety and clinical activity of the combination of azacitidine and pembrolizumab in previously-untreated patients with higher-risk MDS. Methods: Adult patients with untreated intermediate-1- or higher-risk disease by the International Prognostic Scoring System (IPSS) with adequate renal and hepatic function and no prior stem cell transplantation, active autoimmune disease, or immunodeficiencies were eligible for the study. Patients received azacitidine 75 mg/m2 intravenously (IV) or subcutaneously daily for 7 days every 28-day cycle and pembrolizumab 200 mg IV starting on cycle 1 day 1 and every 21 days thereafter independent of the azacitidine dosing schedule. The endpoints were overall response rate, survival, and safety. The criteria for early trial termination included an overall response rate (ORR) < 20%, incidence of grade 3-4 adverse events (AEs) > 30%, poor adherence to protocol and regulatory requirements, severe and adverse drug reactions, and plans to modify or discontinue development of the study drug. Clinical trial information: NCT03094637. Results: At data cut-off (July 2020), 17 therapy-naïve patients have been enrolled and treated with frontline combination azacitidine and pembrolizumab with a median follow-up time of 13.8 months and 5 patients continuing on treatment in cycles 4-28. The median age of patients treated is 71 years (range 36-82), and additional patient characteristics are depicted in Figure A. The overall response rate is 80%, with 3 patients reaching complete remission (CR), 4 patients attaining marrow CR (mCR), 4 patients exhibiting mCR with either hematologic improvement of platelets (HI-P) or erythrocytes (HI-E), and 1 patient demonstrating HI-E. Out of the 12 responders, 7 patients have normal cytogenetics, 1 has del(7q), 1 has del(5q), and 1 has complex karyotype. The most frequently observed mutations in these individuals are TET2 in 5 patients, ASXL1 and SRSF2 in 4 patients each, and RUNX1 and TP53 in 3 patients each. Overall survival was not reached in the frontline HMA + immunotherapy cohort (Figure B). Treatment was overall well-tolerated. The most common treatment-related adverse events (all grades) observed were arthralgias (40%), pneumonia (33%), nausea (27%), and skin rash (27%). One patient died in the first 60 days while receiving treatment from the unrelated cause of ventricular fibrillation. Conclusions: In this phase II trial, preliminary data suggest that combining azacitidine and pembrolizumab was relatively safe and well-tolerated in patients who had never received prior therapy. Though overall survival was not yet reached with the current follow-up time, combination therapy may have antitumor activity in these patients. Figure 1 Disclosures Borthakur: Abbvie: Research Funding; Jannsen: Research Funding; Novartis: Research Funding; Incyte: Research Funding; PTC Therapeutics: Research Funding; Treadwell Therapeutics: Consultancy; Cyclacel: Research Funding; Curio Science LLC: Consultancy; Xbiotech USA: Research Funding; Oncoceutics: Research Funding; BioLine Rx: Research Funding; Polaris: Research Funding; BMS: Research Funding; AstraZeneca: Research Funding; BioLine Rx: Consultancy; PTC Therapeutics: Consultancy; Argenx: Consultancy; FTC Therapeutics: Consultancy; BioTherix: Consultancy; Nkarta Therapeutics: Consultancy; GSK: Research Funding. Daver:Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; 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; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: 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; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cortes:Arog: Research Funding; Amphivena Therapeutics: Research Funding; Astellas: Research Funding; Telios: Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sun Pharma: Research Funding; Takeda: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; BiolineRx: Consultancy, Research Funding; Merus: Research Funding; Immunogen: Research Funding. DiNardo:MedImmune: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Novartis: Consultancy; Notable Labs: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Calithera: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; ImmuneOnc: Honoraria; Syros: Honoraria; Agios: Consultancy, Honoraria, Research Funding. Jabbour:Pfizer: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding. Alvarado:BerGenBio ASA: Research Funding; Tolero Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Daiichi-Sankyo: Research Funding; MEI Pharma: Research Funding; Astex Pharmaceuticals: Research Funding; FibroGen: Research Funding; Sun Pharma: Research Funding. Andreeff:Daiichi-Sankyo; Breast Cancer Research Foundation; CPRIT; NIH/NCI; Amgen; AstraZeneca: Research Funding; Centre for Drug Research & Development; Cancer UK; NCI-CTEP; German Research Council; Leukemia Lymphoma Foundation (LLS); NCI-RDCRN (Rare Disease Clin Network); CLL Founcdation; BioLineRx; SentiBio; Aptose Biosciences, Inc: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo; Jazz Pharmaceuticals; Celgene; Amgen; AstraZeneca; 6 Dimensions Capital: Consultancy; Amgen: Research Funding. Bose:Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene Corporation: Honoraria, Research Funding; Promedior, Inc.: Research Funding; CTI BioPharma: Honoraria, Research Funding; Constellation Pharmaceuticals: Research Funding; Kartos Therapeutics: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; NS Pharma: Research Funding; Pfizer, Inc.: Research Funding; Blueprint Medicines Corporation: Honoraria, Research Funding. Jain:Pfizer: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; BMS: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aprea Therapeutics: Research Funding; Incyte: Research Funding; ADC Therapeutics: Research Funding; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kantarjian:Pfizer: Honoraria, Research Funding; Sanofi: Research Funding; Ascentage: Research Funding; Amgen: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive biotechnologies: Honoraria; Aptitute Health: Honoraria; BioAscend: Honoraria; Delta Fly: Honoraria; Immunogen: Research Funding; Janssen: Honoraria; Oxford Biomedical: Honoraria; Abbvie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz: Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; BMS: Research Funding. Garcia-Manero:Amphivena Therapeutics: Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Jazz Pharmaceuticals: Consultancy; Acceleron Pharmaceuticals: Consultancy, Honoraria; H3 Biomedicine: Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Onconova: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding.

Background: Hypomethylating agents (HMAs) are the standard of care in patients with higher-risk myelodysplastic syndrome (MDS), but the survival of patients after failure of HMA therapy is poor at approximately 4 to 6 months. Expression of PD-1 and PD-L1 was increased in CD34 positive cells from patients with MDS with further upregulation following HMA therapy and HMA failure (Yang H, Leukemia 2014). Pembrolizumab is a humanized monoclonal antibody targeting PD-1, thus blocking its interaction with ligands PD-L1 and PD-L2. A phase 1b, multicohort study of pembrolizumab in advanced hematologic malignancies showed a small number of patients with long-term survival and no immune-mediated adverse events in the higher-risk MDS cohort (Garcia-Manero G, Blood 2016). We report final results from a phase II clinical trial evaluating the safety and clinical activity of azacitidine and pembrolizumab in patients with higher-risk MDS after failure of hypomethylating agent therapy. Methods: Adult patients with intermediate-1- or higher-risk disease by the International Prognostic Scoring System (IPSS) with adequate renal and hepatic function and no prior stem cell transplantation, active autoimmune disease, or immunodeficiencies were eligible for the study. For this HMA failure cohort, patients had to not respond to, progress on, or relapse after at least 6 cycles of HMA therapy. Patients received azacitidine 75 mg/m2 intravenously (IV) or subcutaneously daily for 7 days every 28-day cycle and pembrolizumab 200 mg IV starting on cycle 1 day 1 and every 21 days thereafter independent of the azacitidine dosing schedule. The endpoints were overall response rate, survival, and safety. The criteria for early trial termination included an overall response rate (ORR) < 20%, incidence of grade 3-4 adverse events (AEs) > 30%, poor adherence to protocol and regulatory requirements, severe and adverse drug reactions, and plans to modify or discontinue development of the study drug. Clinical trial information: NCT03094637. Results: At data cut-off (July 2020), 20 patients with HMA failure have been enrolled and treated with combination azacitidine and pembrolizumab with 2 patients continuing on treatment in cycles 30 and 33. The median age of patients treated is 74.5 years, and additional patient characteristics are shown in Figure A. The overall response rate is 25%, with 1 patient achieving complete remission (CR), 2 patients attaining marrow CR (mCR), and 2 patients showing hematological improvement of platelets (HI-P). One of the responders has normal cytogenetics, 1 has del(20q), 1 has del(5q), and 1 has complex karyotype. The most frequently observed mutations in the 5 responding patients are ASXL1 and SETBP1 in 2 patients each. Interestingly, the patient on treatment in cycle 33 has 2 separate TP53 mutations and continues to have stable disease with sustained transfusion independence. With a median follow-up time of 27.9 months, the overall survival is 6.1 months (Figure B). Treatment is overall well-tolerated. The most common treatment-related adverse events (all grades) observed are neutropenia (40%), pneumonia (35%), constipation (30%), and febrile neutropenia (25%). Two patients died in the first 60 days while receiving treatment from the unrelated causes of septic shock and fungal pneumonia. Conclusions: This phase II trial suggests that the combination of azacitidine and pembrolizumab was relatively safe and well-tolerated in patients who had previously failed HMA therapy. Though no significant improvement in overall survival was observed, combination therapy may have antitumor activity in certain HMA failure patients, resulting in sustained responses in some high-risk individuals. Figure Disclosures Borthakur: PTC Therapeutics: Consultancy; GSK: Research Funding; Jannsen: Research Funding; Abbvie: Research Funding; BioLine Rx: Consultancy; BioTherix: Consultancy; Nkarta Therapeutics: Consultancy; Treadwell Therapeutics: Consultancy; Incyte: Research Funding; AstraZeneca: Research Funding; Argenx: Consultancy; FTC Therapeutics: Consultancy; Curio Science LLC: Consultancy; Oncoceutics: Research Funding; Xbiotech USA: Research Funding; Polaris: Research Funding; BioLine Rx: Research Funding; Cyclacel: Research Funding; BMS: Research Funding; Novartis: Research Funding; PTC Therapeutics: Research Funding. Daver:Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: 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; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: 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; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cortes:Immunogen: Research Funding; Merus: Research Funding; Arog: Research Funding; Amphivena Therapeutics: Research Funding; Astellas: Research Funding; Telios: Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sun Pharma: Research Funding; Takeda: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; BiolineRx: Consultancy, Research Funding. DiNardo:MedImmune: Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Syros: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Notable Labs: Membership on an entity's Board of Directors or advisory committees; ImmuneOnc: Honoraria; Calithera: Research Funding; Novartis: Consultancy; Jazz: Honoraria; Takeda: Honoraria. Jabbour:Amgen: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding. Alvarado:FibroGen: Research Funding; BerGenBio ASA: Research Funding; MEI Pharma: Research Funding; Daiichi-Sankyo: Research Funding; Tolero Pharmaceuticals: Research Funding; Sun Pharma: Research Funding; Jazz Pharmaceuticals: Research Funding; Astex Pharmaceuticals: Research Funding. Andreeff:Daiichi-Sankyo; Jazz Pharmaceuticals; Celgene; Amgen; AstraZeneca; 6 Dimensions Capital: Consultancy; Centre for Drug Research & Development; Cancer UK; NCI-CTEP; German Research Council; Leukemia Lymphoma Foundation (LLS); NCI-RDCRN (Rare Disease Clin Network); CLL Founcdation; BioLineRx; SentiBio; Aptose Biosciences, Inc: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Daiichi-Sankyo; Breast Cancer Research Foundation; CPRIT; NIH/NCI; Amgen; AstraZeneca: Research Funding. Bose:Kartos Therapeutics: Honoraria, Research Funding; CTI BioPharma: Honoraria, Research Funding; NS Pharma: Research Funding; Astellas Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Celgene Corporation: Honoraria, Research Funding; Promedior, Inc.: Research Funding; Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer, Inc.: Research Funding; Blueprint Medicines Corporation: Honoraria, Research Funding. Jain:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Incyte: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: 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, Research Funding; BMS: Research Funding; Cellectis: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; Aprea Therapeutics: Research Funding; ADC Therapeutics: Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kantarjian:Pfizer: Honoraria, Research Funding; Sanofi: Research Funding; Abbvie: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Adaptive biotechnologies: Honoraria; Aptitute Health: Honoraria; BioAscend: Honoraria; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Research Funding; Jazz: Research Funding; Immunogen: Research Funding; Delta Fly: Honoraria; Janssen: Honoraria; Oxford Biomedical: Honoraria; Ascentage: Research Funding; BMS: Research Funding; Amgen: Honoraria, Research Funding. Garcia-Manero:Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy; Novartis: Research Funding; H3 Biomedicine: Research Funding; AbbVie: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amphivena Therapeutics: Research Funding; Merck: Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onconova: Research Funding.

Background: The survival of patients with myelodysplastic syndrome (MDS) after hypomethylating agent (HMA) failure is poor at about 4 to 6 months. The exposure of CD34 positive cells from patients with MDS to HMA has been shown to result in increased expression of PD-1 and PD-L1, with a sequential increase in the expression of PD-1 and PD-L1 particularly in patients that have failed HMA (Yang H, Leukemia 2014). Pembrolizumab is a humanized monoclonal antibody targeting PD-1, thus blocking its interaction with ligands PD-L1 and PD-L2, that has been FDA-approved for certain solid tumors. Consequently, we designed an ongoing phase II clinical trial to evaluate the safety and clinical activity of the combination of azacitidine and pembrolizumab in patients with higher-risk MDS. Methods: Adult patients with intermediate-1 or higher disease by the International Prognostic Scoring System (IPSS) were eligible for the study. Patients were divided into two cohorts: those who had not received prior therapy and those who had not responded to, progressed on, or relapsed after HMA therapy, with a goal enrollment of 20 patients per cohort. Patients received azacitidine 75 mg/m2 IV or SQ daily for 7 days on a 28-day cycle and pembrolizumab 200 mg IV starting on cycle 1 day 1 and every 3 weeks thereafter independent of azacitidine dosing schedule. The endpoints were overall response rate and safety. Patients were discontinued from the clinical trial if there was disease progression, unacceptable adverse experiences, intercurrent illness preventing further administration of study treatment, confirmed positive serum pregnancy test, noncompliance, loss to follow-up, completion of 24 months of uninterrupted treatment with pembrolizumab or 35 administrations of the study medication (whichever occurred later), lack of efficacy, or any other reason leading to the investigator's decision for withdrawal. Clinical trial information: NCT03094637. Results: At data cut-off (July 2018), 18 patients have been treated with azacitidine and pembrolizumab with a median follow-up time of 16 weeks and 9 patients continuing on treatment in cycles 1-6. Twelve patients were enrolled in the HMA failure cohort and 6 patients in the previously untreated MDS cohort. Of the 12 patients evaluable for response, 7 were in the HMA failure cohort and 5 in the previously untreated MDS cohort. In the HMA failure cohort, 1 patient achieved CR, 1 patient demonstrated hematological improvement with mCR or CRi, and 5 patients progressed. In the previously untreated MDS cohort, 1 patient attained CR, 2 patients exhibited hematological improvement, 1 patient showed progression, and 1 patient died due to treatment-unrelated causes. The most frequently observed mutations in the 5 responding patients were TET2 in 3 patients and ASXL1, DNMT3A, and RUNX1 in 2 patients each. Three of the responders had diploid cytogenetics, 1 had del(10), and 1 had complex karyotype. Treatment was overall well-tolerated. Most common treatment-related adverse events (all grades) were neutropenia (22%); elevated ALT, elevated AST, anemia, and injection site reactions (17%); and constipation, joint pain, anorexia, pneumonitis, and pneumonia (11%). Conclusions: In this ongoing phase II trial, preliminary data suggest that azacitidine and pembrolizumab was relatively safe and may have antitumor activity in patients who failed HMA. Disclosures Cortes: Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Arog: Research Funding. DiNardo:Karyopharm: Honoraria; Medimmune: Honoraria; Agios: Consultancy; Bayer: Honoraria; Celgene: Honoraria; Abbvie: Honoraria. Daver:Sunesis: Research Funding; ARIAD: Research Funding; BMS: Research Funding; Karyopharm: Research Funding; Incyte: Consultancy; Pfizer: Consultancy; Sunesis: Consultancy; Otsuka: Consultancy; Kiromic: Research Funding; Daiichi-Sankyo: Research Funding; Karyopharm: Consultancy; Novartis: Consultancy; Incyte: Research Funding; Alexion: Consultancy; Novartis: Research Funding; ImmunoGen: Consultancy; Pfizer: Research Funding. Jain:Adaptive Biotechnologioes: Research Funding; Pfizer: Research Funding; Astra Zeneca: Research Funding; Genentech: Research Funding; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Celgene: Research Funding; BMS: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Research Funding; Incyte: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity: Research Funding; Pharmacyclics: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Cellectis: Research Funding; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Research Funding; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding; Genentech: Research Funding; Infinity: Research Funding; Seattle Genetics: Research Funding; ADC Therapeutics: Research Funding; Verastem: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologioes: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees.