Phase 1b Study Of Pembrolizumab Research Articles

PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers.

Small cell neuroendocrine cancers share biologic similarities across tissue types, including transient response to platinum-based chemotherapy with rapid progression of disease. We report a phase 1b study of pembrolizumab in combination with platinum-based chemotherapy in 15 patients with stage III-IV small cell bladder (cohort 1) or small cell/neuroendocrine prostate cancers (cohort 2). Overall response rate (ORR) is 43% with two-year overall survival (OS) rate of 86% (95% confidence interval [CI]: 0.63, 1.00) for cohort 1 and 57% (95% CI: 0.30, 1.00) for cohort 2. Treatment is tolerated well with grade 3 or higher adverse events occurring in 40% of patients with no deaths or treatment cessation secondary to toxicity. Single-cell and Tcell receptor sequencing of serial peripheral blood samples reveals clonal expansion of diverse Tcell repertoire correlating with progression-free survival. Our results demonstrate promising efficacy and safety of this treatment combination and support future investigation of this biomarker. This study was registered at ClinicalTrials.gov (NCT03582475).

Long-term follow-up results from KEYNOTE-041: Phase 1b study of pembrolizumab in Japanese patients with advanced melanoma.

Pembrolizumab demonstrated an acceptable safety profile and promising antitumor activity in Japanese patients with advanced melanoma in the phase 1b KEYNOTE-041 (Study of Pembrolizumab [MK-3475] in Participants With Advanced Melanoma) trial. To evaluate the long-term efficacy and safety of pembrolizumab in Japanese patients with advanced melanoma in KEYNOTE-041. The current analysis reports results of additional follow-up of approximately 12 months since the initial analysis. Eligible patients had locally advanced (unresectable stage III) or metastatic (stage IV) melanoma not amenable to local therapy and had received two or fewer prior systemic therapies. Pembrolizumab 2 mg/kg was given every 3 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points included safety, tolerability, and overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by independent central review. The data cutoff for this analysis was August 30, 2017. Forty-two patients were followed up for a median of 22.3 months (range, 2.63-30.82 months). The ORR was 24.3% (nine of 37 evaluable patients [95% confidence interval (CI), 11.8%-41.2%]). Two patients with partial response at the time of the initial analysis achieved complete response. The median overall survival (OS) was 25.1 months (95% CI, 13.1-not reached] and the 30-month OS rate was 46.3% (95% CI, 29.8%-61.3%). The median duration of response was not reached. Treatment-related adverse events (TRAEs) were reported in 78.6% of patients; the incidence of grade 3 to 5 TRAEs was 23.8%. No additional treatment-related deaths occurred since the initial analysis. Pembrolizumab provided durable antitumor activity and an acceptable safety profile in Japanese patients with advanced melanoma.

Pembrolizumab in combination with epigenetic therapy is safe and active in heavily treated patients with peripheral T‐cell lymphoma and cutaneous T‐cell lymphoma

Introduction: Peripheral T-cell lymphomas are uniquely sensitive to epigenetic modifiers. We have shown that decitabine and 5-azacytidine (Marchi et al.; Br. J. Haematol. 171; 2015) induce the expression of cancer testis antigens in pre-clinical models of PTCL, and that pralatrexate modulates genes involved in cytokine production, viral response and apoptosis. These data suggest a role for the incorporation of the immune-checkpoint inhibitor, pembrolizumab, to epigenetic agents. Herein we report on the clinical activity of this approach in patients with relapsed or refractory (R/R) PTCL and CTCL. Methods: This is a phase 1b study of pembrolizumab combined with pralatrexate (Arm A), pralatrexate + decitabine (Arm B), or decitabine (Arm C) in patients with R/R PTCL and CTCL. A 3+3 dose-escalation/de-escalation is applied in Arms A and C while a DLT-adapted partial order continual reassessment method for dose-finding with combinations of agents is applied in Arm B. Changes in serum cytokine levels were assessed during cycle 1 using a Luminex-based immunoassay. T-cell subpopulation profiling in peripheral blood was performed using a multi-color flow cytometry assay (Cytek® Aurora). Results: Patient characteristics, toxicity data, and response analysis are shown in table 1. Serum levels of three cytokines, TNFα, MIP-3α and IL-10, measured at day 1 pre-treatment were significantly elevated (p = 0.0001, 0.011 and 0.0017, respectively) in trial patients compared to healthy controls. Patients who responded to treatment demonstrated a more consistent decline in levels of TNFα, MIP-3α, and IL-10 during cycle 1, whereas non-responders showed stable to increased levels of these cytokines. T-cell subpopulation analysis (n = 6) showed mean CD4:CD8 ratio of 0.5 in trial patients prior to treatment compared to 1.5 for healthy age and sex-matched controls (p = 0.016). No significant change in the proportion of PD1+CD8+ central memory cells was seen in trial patients between D0 and D28 of treatment (p = 0.12), and between D0 in comparison to healthy controls (p = 0.11). The proportion of PD1+CD8+ effector T cells was lower in trial patients relative to healthy controls both before and after treatment (p = 0.04 and 0.001, respectively). There was no difference in the proportion of PD1+CD8+ effector T cells among trial patients from D0 to D28 of treatment (p = 0.19). Patients who responded to treatment (n = 3), had a lower proportion of PD1+ CD8+ effector cells at the start of treatment relative to non-responders (p = 0.002). Conclusions: These clinical data suggest that the integration of pembrolizumab on an epigenetic backbone is safe and demonstrates encouraging responses in heavily treated patients with PTCL and CTCL. These correlative data suggest that specific cytokines (TNFα, MIP-3α, and IL-10) and changes in circulating T-cell subpopulations may have predictive value as biomarkers of disease response. The research was funded by: Merck and Co. Ongoing Trial Keywords: Aggressive T-cell non-Hodgkin lymphoma, Combination Therapies, Ongoing Trials Conflicts of interests pertinent to the abstract. N. N. Benani Consultant or advisory role: Vividion Therapeutics, Kymera, Secura Bio, Affirmed GmbH, Astellas Pharma, Acrotech Biopharma LLC M. E. Williams Consultant or advisory role: Astra Zeneca, Gilead, Janssen, Kite Pharma, Kymera, TG Therapeutics Honoraria: International Oncology Network, Research to Practice Research funding: Janssen, Kymera, Pharmacyclics J. S. Manavalan Research funding: Astex O. A. O'Connor Employment or leadership position: TG Therapeutics Stock ownership: TG Therapeutics E. Marchi Employment or leadership position: Myeloid Therapeutics Consultant or advisory role: Myeloid Therapeutics Honoraria: Kyowa Kirin Research funding: Merck and Co., Celgene/BMS, Astex, NomoCan Pharmaceuticals Other remuneration: University of Virginia (Patents & Royalties: 3062/170 PROV), Daiichi Sankyo (advisory board)

Promising Safety and Efficacy Results from an Ongoing Phase 1b Study of Pembrolizumab Combined with Decitabine in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

BACKGROUND: For AML patients (pts) deemed ineligible for intensive cytotoxic chemotherapy, hypomethylating agents (HMA) have been established as standard treatment. Decitabine 20 mg/m2 on days 1-10 per 28 day cycle has demonstrated single agent efficacy with 15% complete remission (CR)/CR with incomplete hematologic recovery (CRi) in R/R AML (Khan et al. Leuk Lymphoma 2017). In a phase 2 trial, 10-day decitabine with venetoclax demonstrated overall response rate (ORR) of 62% in R/R AML (Dinardo C et al. Lancet Haematol 2020). However, aberrant upregulation of PDL1 and PD-L2 has been observed in 25% and 33% of CD34+ samples from AML pts respectively (Plass C et al. Semin Oncol 2008). Pts resistant to epigenetic therapy had relative higher increments in gene expression of PD-L1, PD-L2 and CTLA4 compared with pts who achieved response, suggesting that PD-1 signaling may be involved in resistance mechanisms to HMA. In a prior phase 2 trial evaluating pembrolizumab and azacitidine in R/R AML, responses among 29 evaluable pts demonstrated ORR 17.2% (Gojo I et al. Blood 2019). In this phase 1b trial, we set out to test the combination of pembrolizumab and decitabine (NCT03969446). METHODS: Pts [≥18 years old (yo); ECOG ≤1] with R/R AML not eligible for allogeneic hematopoietic cell transplantation (alloHCT), received decitabine 20 mg/m2 on days 1-10. If in CR/CRi, decitabine was reduced to days 1-5 of cycles 3+. Pembrolizumab was given on days 1 and 22 in all cycles. Cycle length was 42 days. This phase 1b study has two arms, AML and myelodysplastic syndromes (MDS) with primary objectives of safety, tolerability, recommended phase 2 dose (RP2D) and to obtain preliminary estimates of CR/CRi rate using the "3+3" design. Here, we provide interim safety and efficacy data for the first 6 pts on the AML arm. RESULTS: As of July 1, 2022, 6 pts were enrolled to the AML arm cohort 1. The six treated and evaluable pts received a median of 2 (range: 1-7) cycles of treatment. At baseline, the median age was 78 yo (range: 72-81) with median 2 (range: 1-4) prior lines of regimens, and median 35% (7-65) bone marrow blasts. All pts had previously progressed on decitabine and venetoclax. All-non-hematologic grade 3 toxicities were reversible. No dose limiting toxicity, ≥ gr4 non-hematologic toxicity, or treatment related deaths were seen. Most common Grade (Gr) 3-4 treatment-related hematologic toxicities were: anemia (100%), febrile neutropenia (83%), lymphopenia (100%), and thrombocytopenia (100%). Most common infectious toxicities included Gr 3 lung infections (50%). Three pts (50%) achieved CR/CRi, 1 pt (16.7%) achieved partial remission, and 2 pts (33%) achieved stable disease. ORR was 66.7% in this cohort. The median follow-up time is 19.8 months (4.1-22.6), with 4 pts still alive at the data cut -off. One pt was able to bridge to alloHCT. CONCLUSIONS: The combination of pembrolizumab and decitabine in the AML arm cohort 1 of this study in pts with R/R AML was deemed safe with manageable side effect profile and encouraging anti-leukemic activity and offers potential for promising therapy for R/R AML that progress even after prior HMA therapy. Furthermore, this study demonstrates the effectiveness of the 10-day decitabine schedule. The study is now open for the MDS arm, with treatment of the same schedule of pembrolizumab in combination with decitabine 20 mg/m2 on days 1-5 of each cycle. The study has also been amended to include AML cohort 2 to add venetoclax to the decitabine/pembrolizumab regimen and pts are now being enrolled on this arm.

Pembrolizumab in Combination with Epigenetic Therapy Is Safe and Active in Heavily Treated Patients with Peripheral T-Cell Lymphoma (PTCL) and Cutaneous T-Cell Lymphoma (CTCL): Preliminary Results from the Embolden Trial

Background: Peripheral T-cell lymphomas (PTCLs) are uniquely sensitive to epigenetic modifiers. Our group previously demonstrated that combinations of epigenetic modifiers such as histone deacetylase inhibitors (HDACi), hypomethylating agents and pralatrexate produced potent synergy in pre-clinical models of PTCL, which produced compelling activity in early phase clinical studies. We have demonstrated that epigenetic modifiers, such as decitabine and 5-azacytidine (Marchi et al; Br. J. Haematol. 171, 2015) induces the expression of cancer testis antigens and established that pralatrexate acts as an immunomodulatory agent affecting genes involved in cytokine production, viral response and apoptosis. These pre-clinical data suggest a role for the incorporation of the immune-checkpoint inhibitor, pembrolizumab, to epigenetic backbones. Herein, we report on the differential clinical activity of adding the immune checkpoint inhibitor, pembrolizumab, to decitabine, pralatrexate, or the combination and we describe the role of cytokines as a biomarker of treatment response. Trial Design & Methods: This is a phase 1b study of pembrolizumab combined with pralatrexate alone (Arm A), with pralatrexate + decitabine (Arm B), or decitabine alone (Arm C) in patients with relapsed and refractory PTCL and CTCL. A standard 3+3 dose-escalation was applied in the doublet Arms (A and C) while a DLT-adapted partial order continual reassessment method (POCRM) for dose-finding with combinations of agents was applied in the triplet Arm (Arm B). We evaluated the cytokine profile using a Luminex-based immunoassay on serum samples obtained from trial patients on days 1, 8 and 15 during cycle 1 of treatment. Quantitative changes in 25 unique cytokines were evaluated, and these changes were correlated with clinical outcomes. Results: We enrolled 15 patients with six patients in Arm A, four in Arm B, and five in Arm C. All patients that received at least one dose of drug were evaluable for toxicity. One dose limiting toxicity (DLT) was observed in Arms A and B (grade 3 thrombocytopenia and febrile neutropenia, respectively). In Arm C, three DLTs were observed including one patient with grade 3 hyponatremia and rash; one patient with grade 4 thrombocytopenia, neutropenia, and anemia; and one patient with grade 4 neutropenia. There were no treatment related deaths. Nine patients out of 15 were evaluable for response at the time of this analysis. Of these nine evaluable patients, one achieved a complete remission (Arm B), two achieved partial remission (1 in Arm A, 1 in Arm B), one had stable disease (Arm C), and five experienced disease progression (2 in Arm A, 1 in Arm B, and 2 in Arm C). Interestingly, two of the three responses were seen in patients who received the triplet of pralatrexate, decitabine, and pembrolizumab (Arm B) and one response was seen in a patient treated with pralatrexate and pembrolizumab (Arm A). The serum cytokine profile revealed significant changes in only five of the 25 cytokines surveyed. Of the five cytokines, three pro-inflammatory cytokines, TNFα, MIP-3α and IL-10, measured at day 1 pre-treatment exhibited significantly higher levels (p= 0.0001, 0.0008 and 0.003 respectively) compared to healthy controls. Trial patients who responded to treatment (PR/CR) in either Arms demonstrated a decline in serum levels of TNFα and IL-10 by day 15 of cycle 1, whereas non-responders (PD/SD) showed stable to increased levels of both TNFα (Figure 1) and IL-10. Conclusion: These preliminary data suggest that the integration of pembrolizumab into an epigenetic backbone is safe and demonstrates encouraging responses in heavily pretreated patients with PTCL and CTCL. Pharmacodynamic data suggests that certain cytokines might have predictive value as biomarkers of disease response and progression. Interestingly, patients that responded (PR/CR) to the study drugs displayed a decline in cytokine levels, highlighting the prognostic implications of these cytokines. Additional pharmacodynamic studies, including flow cytometry of peripheral blood mononuclear cells, and pharmacokinetic studies are ongoing. Clinical trial registry NCT03240211. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Integration of PD1 blockade with epigenetic therapy is highly active and safe in heavily treated patients with T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).

8049 Background: Our group has demonstrated that combinations of epigenetic modifiers produce potent synergy in pre-clinical models of PTCL and induce the expression of cancer testis antigen, suggesting a role in the addition of the immune-checkpoint inhibitor, pembrolizumab. Methods: This is a phase 1b study of pembrolizumab combined with pralatrexate alone (Arm A), with pralatrexate + decitabine (Arm B), or decitabine alone (Arm C) in patients with relapsed and refractory PTCL and CTCL. A standard 3+3 dose-escalation is applied in the triplet Arm (Arm B) while in the doublet Arms (A and C) de-escalation is applied in case of toxicity. Pharmacokinetic and pharmacodynamic studies are ongoing. Results: We treated a total of 12 patients with 4 patients in each Arm. All patients that received at least one dose of drug were evaluable for toxicity. There was a dose limiting toxicity (DLT) in each arm including prolonged grade 3 thrombocytopenia (Arm A), febrile neutropenia (Arm B), grade 3 hyponatremia, and rash (Arm C). There were no treatment-related deaths. Six patients out of 12 were evaluable for response at the time of this analysis. One patient achieved a complete remission, 2 had partial remission, 1 had stable disease, and 2 experienced progression of disease. Interestingly, all of the responses were seen in the triple combination of pralatrexate, decitabine, and pembrolizumab. Table summarizes the patient characteristics, toxicities, and response rates. Conclusions: These preliminary clinical data suggest that the integration of pembrolizumab on an epigenetic backbone is safe and demonstrates encouraging responses in patient with PTCL and CTCL. Clinical trial information: 03240211 . [Table: see text]

Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041)

PurposeThis phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma.MethodsPembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review.ResultsForty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3–5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3–5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3–43.5) for cutaneous melanoma and 25.0% (95% CI 3.2–65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma.ConclusionThe safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.

Pembrolizumab, a PD-1 Inhibitor, in Patients with Myelodysplastic Syndrome (MDS) after Failure of Hypomethylating Agent Treatment

▪Background: Upregulation of the immune checkpoint receptor PD-1 and its ligands, PD-L1 and PD-L2, has been demonstrated in peripheral blood mononuclear cells from patients with MDS (Yang H et al. Leukemia2014;28:1280-1288). This upregulation is enhanced by epigenetic modifiers, such as 5-azacitidine, and has been associated with poor survival. The PD-1 pathway thus represents an attractive target in patients with MDS that has failed first-line treatment with a hypomethylating agent. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands and can restore antitumor immune activity in solid tumors and hematologic malignancies. KEYNOTE-013 (NCT01953692) is a multicenter, multicohort phase 1b study of pembrolizumab in patients with hematologic malignancies. Results from the MDS cohort of KEYNOTE-013 are presented.Methods: Key eligibility criteria for this cohort included age ≥18 years, primary or secondary MDS with IPSS score of intermediate 1, intermediate 2, or high; and failure (defined as worsening of cytopenias, increase in percentage of bone marrow blasts, or progression to more advanced MDS FAB subtype than at pretreatment) to respond to at least 4 cycles of prior treatment with a hypomethylating agent (azacitidine or decitabine). Pembrolizumab was administered intravenously at a dose of 10 mg/kg every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Response was assessed by investigator every 6 weeks using IWG 2006 criteria (Cheson BD et al. Blood2006;108:419-425). The primary end points were safety and objective response rate; secondary objectives included overall survival, bone marrow response, and hematologic improvement. Bone marrow samples were collected at predefined time points during the study for analysis of gene expression profiles with the NanoString platform.Results: Among the 28 patients enrolled in the MDS cohort, median age was 73 years (range, 38-84 years), 64% were male, and IPSS scores were intermediate 1 in 10 patients (36%), intermediate 2 in 9 patients (32%), and high in 7 patients (25%). 54% of patients had a FAB classification of refractory anemia with excess blasts. At the time of data cutoff on May 27, 2016, the median follow-up duration was 5.6 months (range, 1-29 months). 10 patients (36%) experienced treatment-related adverse events (AEs); the most frequent were hypothyroidism in 4 patients (14%) and fatigue in 3 patients (11%). Grade 3/4 treatment-related AEs occurred in 2 patients (7%), including grade 3 gastroenteritis and grade 4 tumor lysis syndrome in 1 patient each. 2 patients discontinued because of treatment-related AEs, including grade 4 tumor lysis syndrome in 1 patient, and grade 2 arthralgia, grade 1 musculoskeletal stiffness, and grade 1 peripheral edema in 1 patient. There were no treatment-related deaths. Of the 27 patients evaluated for efficacy, there were no complete remissions (CRs), and 1 patient achieved a partial remission, for an overall response rate of 4% (90% CI, 0.2%-16%). Among the remaining patients, best overall response was marrow CR in 3 patients (11%), stable disease in 14 patients (52%), and progressive disease in 9 patients (33%). Hematologic improvement was seen in 3 patients (11%). The overall survival rate at 24 weeks was 49% across the cohort, including 89% in patients with intermediate 1 IPSS score, 22% in patients with intermediate 2 IPSS score, and 29% in patients with high IPSS score. For patients with intermediate 1 score, the 1-year overall survival rate was 89%; the 2-year overall survival rate was 57%. Biomarker data will be presented.Conclusion: PD-1 blockade with pembrolizumab was associated with a manageable safety profile and potential clinical activity in patients with MDS after failure of first-line treatment with a hypomethylating agent. Future studies in combination with azacitidine are planned. DisclosuresMartinelli:MSD: Consultancy; Amgen: Consultancy; Roche: Consultancy; ARIAD: Consultancy; Pfizer: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau; Genentech: Consultancy. Ribrag:Pharmamar: 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; ArgenX: Research Funding; Gilead: Membership on an entity’s Board of Directors or advisory committees; Infinity: Membership on an entity’s Board of Directors or advisory committees; Esai: Membership on an entity’s Board of Directors or advisory committees; Nanostring: Membership on an entity’s Board of Directors or advisory committees; Incyte: Membership on an entity’s Board of Directors or advisory committees. Balakumaran:Merck & Co.: Employment, Other: stock, stock options. Chlosta:Merck & Co., Inc.: Employment, Other: stock, stock options. Zhang:Merck & Co., Inc.: Employment, Other: stock, stock options. Smith:Celgene: Consultancy, Other: member of DSMB.

Phase 1b Study of Pembrolizumab in Patients with Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Results from the Ongoing Keynote-013 Trial

Phase 1b Study of Pembrolizumab in Patients with Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Results from the Ongoing Keynote-013 Trial

1221P - KEYNOTE-025: Phase 1b study of pembrolizumab (pembro) in Japanese patients (pts) with previously treated PD-L1+ non-small cell lung cancer (NSCLC)

1221P - KEYNOTE-025: Phase 1b study of pembrolizumab (pembro) in Japanese patients (pts) with previously treated PD-L1+ non-small cell lung cancer (NSCLC)

A Phase 1B Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Advanced Gastric Cancer

ABSTRACT Aim: The PD-1 receptor-ligand pathway can be used by tumors to evade immune surveillance, thereby allowing neoplastic growth. Pembro is a highly selective, humanized IgG4/kappa isotype monoclonal antibody designed to block PD-1 interaction with its ligands PD-L1 and PD-L2, thus reactivating the immune system to eradicate the host tumor. In a phase 1b study (Clinicaltrials.gov: NCT01848834), we assessed the safety, tolerability, and antitumor activity of pembro in gastric cancer pts. Methods: Using a prototype immunohistochemistry assay, PD-L1 expression was assessed in archival tumor samples from pts with recurrent/metastatic adenocarcinoma of the stomach or gastroesophageal junction. Eligible pts with PD-L1 staining in stroma or ≥1% of tumor cells were enrolled and treated with pembro 10 mg/kg every 2 weeks for up to 24 months or until complete response, disease progression, or unacceptable toxicity. Enrollment was designed to include an equal number of pts from Asia Pacific (AP) and the rest of the world (ROW). Adverse events (AEs) were monitored and graded per the NCI CTCAE v4.0. Radiographic imaging was performed every 8 weeks. Primary efficacy end point was overall response rate (ORR) assessed by RECIST v1.1. Results: Of the 162 pts screened, 65 (40%) were PD-L1+ and 39 enrolled: 19 from AP, 20 from ROW. Median age was 63 y, and 72% of pts were men. Pts from AP were more heavily pretreated than pts from ROW (≥2 prior therapies in 79% vs 55%). Median follow-up duration was ∼6 mo. The most common AEs deemed treatment related by investigators were hypothyroidism and fatigue (n = 5 each). Grade ≥3 AEs deemed treatment related occurred in 3 pts (n = 1 each for hypoxia, peripheral neuropathy, and pneumonitis). ORR (confirmed + unconfirmed) was 32% in AP and 30% in ROW. Responses were ongoing for 6/6 AP pts and 5/6 ROW pts (median response duration not reached; range 8+ to 20+ wk). Evidence of an association between PD-L1 expression and PFS (P = 0.032) and ORR (P = 0.071) was observed. Conclusions: Pembro was generally well tolerated by and provided antitumor activity in pts with advanced gastric cancer that expressed PD-L1. The robust antitumor activity observed supports the further development of pembro in advanced gastric cancer. Disclosure: E.J. Gonzalez: Is employee of and holds stock in Merck & Co., Inc.; J. Pulini: Is former employee of Merck & Co., Inc.; A.B. Ray, M. Dolled-Filhart, K. Emancipator, K. Pathiraja, X. Shu and M.R. Koshiji: Is an employee of Merck & Co., Inc.; J. Cheng: Is an employee of and holds stock in Merck & Co., Inc. All other authors have declared no conflicts of interest.