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).
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).
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).
Avelumab showed acceptable safety and clinical activity in Japanese pts with advanced GC/GEJC progressed after chemotherapy.
Clinical trial identification
EMR 100070-002 (NCT01943461).
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Merck KGaA, Darmstadt, Germany and Pfizer.
Medical writing support was provided by Clinical Thinking Inc, Hamilton, NJ, USA.
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.