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. Electronic supplementary material The online version of this article (10.1007/s10120-018-0903-1) contains supplementary material, which is available to authorized users.

Changing Body Weight–Based Dosing to a Flat Dose for Avelumab in Metastatic Merkel Cell and Advanced Urothelial Carcinoma

“…Thus, the exposures expected with flat dosing of avelumab are within the exposure range of a weight‐based dose that has shown clinical activity and an acceptable safety profile. In addition, simulated exposure with the 800 mg dose was markedly lower than that observed with a 20 mg/kg dose, which has shown acceptable safety and tolerability in 2 phase I trials …”

“…In the initial dose‐escalation part, patients received avelumab at 3, 10, or 20 mg/kg q2w. In the dose‐expansion part, patients with advanced/metastatic gastric or gastroesophageal cancer received avelumab at 10 mg/kg q2w …”

“…The first phase I trials of avelumab as monotherapy were JAVELIN Solid Tumor (NCT01772004), a large, global study, and JAVELIN Solid Tumor JPN (NCT01943461), performed in Japan . Both studies included an initial dose‐escalation part.…”

“…The approval of avelumab 10 mg/kg in patients with mMCC was based on results from JAVELIN Merkel 200 (NCT02155647, a separate single‐arm phase II study that included a cohort of 88 patients with stage IV chemotherapy‐refractory mMCC who received avelumab 10 mg/kg every 2 weeks (q2w)) . Single‐dose PK for avelumab was reported from the dose‐escalation parts of JAVELIN Solid Tumor and JAVELIN Solid Tumor JPN . Population PK models have been developed that show a modest effect of body weight on CL and a potential shallow exposure‐response relationship in some tumor types …”

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

“…Avelumab showed a manageable safety profile in Japanese patients with advanced solid tumors and clinical activity in patients with advanced gastric cancer/gastroesophageal junction cancer that had progressed after chemotherapy in the phase 1 JAVELIN Solid Tumor JPN trial. 10 Avelumab was also approved for curatively unresectable Merkel cell carcinoma in Japan in September 2017.…”