Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN Solid Tumor JPN trial

Abstract

Background: Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in several advanced cancers. We report results from JAVELIN Solid Tumor JPN, a phase 1 trial of avelumab in Japanese patients with advanced solid tumors with expansion in patients with advanced gastric cancer/gastroesophageal junction cancer.

Methods: In the dose-escalation part, eligible patients had various previously treated metastatic or advanced solid tumors. In the dose-expansion part, patients had stage IV gastric cancer/gastroesophageal junction adenocarcinoma and disease progression after prior therapy that included a platinum and fluoropyrimidine agent. Patients received avelumab every 2 weeks intravenously at 3, 10, or 20 mg/kg during dose escalation and 10 mg/kg during dose expansion.

Results: Among 17 patients who received avelumab in the dose-escalation part, no dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. 40 patients were enrolled in the dose-expansion part, of whom 21 (52.5%) had received ≥ 3 prior lines of therapy for advanced disease. In these patients, the objective response rate was 10.0% (95% CI, 2.8-23.7%) and median overall survival was 9.1 months (95% CI, 7.2-11.2 months). Three of 40 patients (7.5%) had a grade 3 treatment-related adverse event (alanine aminotransferase increase, anemia, and hyponatremia), and no grade ≥ 4 treatment-related adverse events occurred. Five patients (12.5%) had an immune-related adverse event (all grade 1/2).

Conclusions: Avelumab showed acceptable safety in Japanese patients with advanced solid tumors and clinical activity in patients with advanced gastric cancer/gastroesophageal junction cancer and disease progression after chemotherapy.

Keywords: Avelumab; Gastric cancer; Japan; PD-L1; Phase 1.

Conflict of interest statement

TD has received research funding from AbbVie, Astellas Pharma, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai Pharma, Daiichi Sankyo, IQVIA, Janssen, Kyowa Hakko Kirin, Lilly Japan, MSD, Merck Serono, Novartis, Pfizer, Sumitomo Group Takeda, and Taiho Pharmaceutical, and reports consulting roles for Amgen, Chugai Pharma, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly Japan, MSD, Sumitomo Dainippon, and Taiho Pharmaceutical. SI reports honoraria from Chugai Pharma and Takeda, and has received research funding from AbbVie, AstraZeneca, Astellas, Bayer, Chugai Pharma, Daiichi Sankyo, Eisai, Lilly, Merck Serono, Nano Carrier, Novartis, Ono Pharmaceutical, Otsuka, Sanofi, Sumitomo Dainippon, Taiho Pharmaceutical, and Teijin. KM reports honoraria from Chugai Pharma, Merck Serono, Takeda, Taiho Pharmaceutical, and Yakult. TS reports honoraria and consulting or advisory roles for Bristol-Myers Squibb, Chugai Pharma, and Merck Serono; TS also reports consulting or advisory roles for Lilly and has received research funding from Chugai Pharma and Yakult. SH reports honoraria from Novartis, Taiho Pharmaceutical, Takeda, and Yakult, and reports consulting or advisory roles for Lilly and Yakult. TE has received research funding from Merck Serono. TN reports honoraria from Merck Serono. HH reports honoraria from Chugai Pharma, Lilly, Merck Serono, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, and Yakult, and reports consulting or advisory roles from Chugai Pharma, MSD, Merck Serono, and Ono Pharmaceutical. HH has received research funding from AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Eisai, Incyte, Lilly, LSK BioPharma, MSD, Merck Serono, Ono Pharmaceutical, Pfizer, Sumitomo Dainippon, Taiho Pharmaceutical, and Takeda. NM and SO have no disclosures to report. YK reports honoraria and speaker services for Bayer, Novartis, and Pfizer; YK also reports speaker services for Chugai Pharma, Lilly, Merck Serono, and Taiho Pharmaceutical, and research funding from Bayer, Chugai Pharma, Lilly, MSD, Novartis, Ono Pharmaceutical, Taiho, and Yakult. YS reports honoraria from Bayer Yakuhin, Chugai Pharma, Daiichi Sankyo, Lilly, Merck Serono, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, and Yakult; YS has also received research funding from Chugai Pharma, Lilly, Merck Serono, MSD, and Taiho Pharmaceutical. SS and MW are employees of Merck Serono.

Figures

Fig. 1

Antitumor activity of avelumab in patients with GC/GEJC in the dose-expansion cohort (N = 40). a Time to and duration of response in responding patients (n = 4). b Best change in target lesions from baseline by PD-L1 status (≥ 1% cutoff; n = 38 evaluable). c Change in target lesions from baseline over time by PD-L1 status (≥ 1% cutoff; n = 38 evaluable)

Fig. 2

Kaplan–Meier estimates of a progression-free survival and b overall survival in patients with GC/GEJC in the dose-expansion cohort (n = 40)