Avelumab (anti–PD-L1) in Japanese patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC): Updated results from the phase Ib JAVELIN solid tumour JPN trial

Background: Avelumab, a human anti–PD-L1 IgG1 monoclonal antibody that can induce innate effector function against tumor cells in preclinical models, is an approved treatment for metastatic Merkel cell carcinoma in various countries and platinum-treated advanced urothelial carcinoma in the US and Canada. We report updated results from the dose-expansion part of a phase 1b trial of avelumab in Japanese patients (pts) with advanced GC/GEJC (NCT01943461). Methods: Pts had stage IV GC/GEJC adenocarcinoma and progression after 1 or 2 prior lines of chemotherapy including a platinum and fluoropyrimidine agent (initially enrolled pts) or progression after platinum/fluoropyrimidine followed by a taxane or irinotecan (later pts). Pts received avelumab 10 mg/kg Q2W by IV infusion until confirmed progression, unacceptable toxicity or withdrawal. PD-L1 expression was assessed using the Dako PD-L1 IHC 73-10 assay (≥1% tumor cell cutoff). Results: At data cutoff on Aug 10, 2016, 40 pts had received avelumab (median treatment duration 2.7 mo; range 0.5–21.4). 21 pts (52.5%) had received ≥3 prior lines of therapy for advanced disease. The objective response rate (ORR) was 10.0% (95% CI 2.8–23.7), including complete response in 1 pt and partial response in 3 pts. 17 pts had stable disease as best response and the disease control rate was 52.5%. Median progression-free survival was 2.5 mo (95% CI 1.4–2.8). Median overall survival (OS) was 9.1 mo (95% CI 7.2–11.2) and the 12-mo OS rate was 31.0% (95% CI 15.6–47.8). In evaluable pts with PD-L1 + (n = 11) or PD-L1 − (n = 27) tumors, ORR was 27.3% and 3.7%, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 32 pts (80.0%), including infusion-related reaction (27.5%; all grade 1/2), pruritus (15.0%), pyrexia (12.5%) and rash (10.0%) in ≥ 10% of pts. Grade 3 TRAEs occurred in 3 pts (7.5%; ALT increase, anemia and hyponatremia); no pt had a grade ≥4 TRAE. 5 pts had an immune-related AE (all grade 1/2); the most common were pruritus (n = 3) and maculopapular rash (n = 2). Conclusions: Avelumab showed acceptable safety and clinical activity in Japanese pts with advanced GC/GEJC progressed after chemotherapy. Clinical trial identification: EMR 100070-002 (NCT01943461). Editorial acknowledgement: Medical writing support was provided by Clinical Thinking Inc, Hamilton, NJ, USA. Legal entity responsible for the study: Merck KGaA, Darmstadt, Germany. Funding: Merck KGaA, Darmstadt, Germany and Pfizer. Disclosure: T. Doi: Consultancy (Includes expert testimony): Lilly, Japan Chugai Pharma, Kyowa, Hakko, Kirin, MSD, Daiichi Sankyo, Amgen, Sumitomo, Dainippon, Taiho Pharmaceutical; Research funding: Taiho Pharmaceutical, Novartis, Merck Serono, Astellas Pharma, MSD, Janssen, Boehringer Ingelheim, Takeda, Pfizer, Lilly, Japan Sumitomo Group, Chugai Pharma, Kyowa, Hakko, Kirin, Daiichi Sankyo, Celgene, Bristol-Myers Squibb, Abbvie, Quintiles. S. Iwasa: Honoraria: Chugai, Takeda; Research funding for institution: Otsuka, Taiho, Chugai, AstraZeneca, Novartis, Sanofi, Ono, Eli Lilly, Merck Serono, Daiichi-Sankyo, Nano Carrier, Teijin Pharma, Dainippon-Sumitomo, Astellas, Bayer, Abbvie, Eisai. K. Muro: Honoraria: Chugai, Taiho, Merck Serono, Yakult, Takeda. T. Satoh: Honoraria: Merck-Serono, Bristol-Myers Squibb, Chugai Pharmaceutical; Consulting or advisory role: Chugai Pharmaceutical, Eli Lilly, Merck Serono, Bristol-Myers Squibb; Research funding: Chugai Pharmaceutical, Yakult Honsha. S. Hironaka: Honoraria: Taiho, Yakult Honsha, Takeda, Novartis; Consulting or advisory role: Eli Lilly, Yakult Honsha. T. Esaki: Research funding: Merck Serono. T. Nishina: Honoraria: Merck Serono. H. Hara: Honoraria: Chugai Pharma; Taiho Pharmaceutical, Merck Serono, Yakult Honsha, Lilly, Ono Pharmaceutical, Takeda; Consulting or Advisory role: Ono Pharmaceutical, Chugai Pharma, Merck Serono, MSD; Research Funding for institution: AstraZeneca, Chugai Pharma, Merck Serono, MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Boehringer Ingelheim, Dainippon Sumitomo Pharma, Daiichi Sankyo, Lilly, Pfizer, LSK Biopharma, Eisai, Incyte. Y. Komatsu: Honoraria: Novartis, Pfizer, Bayer; Speakers' bureau: Taiho, Lilly, Chugai, Merck, Novartis, Pfizer, Bayer; Research funding: Taiho, Lilly, MSD, Ono, Novartis, Bayer, Chugai, Yakult. S. Shimizu: Employee: Merck Serono Co, Ltd. V. Chand: Employee: EMD Serono Research & Development Institute, Inc; Stock Shareholder: Bristol-Meyers Squibb M. Watanabe: Employee: Merck Serono Co., Ltd. All other authors have declared no conflicts of interest.

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