P-282 JAVELIN Gastric 300: Phase 3 trial of avelumab (anti-PD-L1 antibody) + best supportive care (BSC) vs BSC ± chemotherapy as third-line treatment for advanced gastric or gastroesophageal junction cancer

Abstract

Introduction: In patients with gastric cancer that progressed following second-line chemotherapy, there is currently no standard of care. Single-agent chemotherapy is used, but has not demonstrated a survival advantage over best supportive care (BSC). Prognosis is poor and toxicity from chemotherapy may contribute to the limited benefit and cumulative risk for these late-line patients. Programmed death-1 receptor ligand (PD-L1) is a key therapeutic target in the reactivation of the immune response against multiple cancers. Avelumab∗ (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody that has shown promising efficacy and an acceptable safety profile in patients with various tumor types. In two phase 1 trials (JAVELIN Solid Tumor and JAVELIN Solid Tumor JPN), avelumab 10 mg/kg administered every 2 weeks (Q2W) showed antitumor activity in patients with advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC) as maintenance therapy in non-progressing patients after first-line chemotherapy and as second-line treatment. This randomized phase 3 trial, JAVELIN Gastric 300 (NCT02625623), compares avelumab + BSC vs BSC ± chemotherapy as third-line treatment for patients with GC/GEJC. Methods: JAVELIN Gastric 300 is an open-label, global, multicenter trial. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, best overall response, quality of life (assessed via EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-STO22 questionnaires), and safety. Additional endpoints include duration of response, time to response, and association between PD-L1 expression in tumor cells or immune cells within the tumor microenvironment (measured by immunohistochemistry) and clinical responses. Responses are evaluated according to RECIST 1.1 every 6 weeks and adjudicated by a blinded independent review committee. Adverse events are assessed throughout the trial. Key eligibility criteria are: histologically confirmed, unresectable, locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction; age ≥18 years; ECOG performance status score of 0 or 1; progression after two prior lines of systemic treatment, no prior therapy with any drug targeting T cell coregulatory proteins, and no concurrent anticancer treatment or immunosuppressive agents. Fresh or archival tumor tissue for PD-L1 expression assessment is required for all patients, but patients are not preselected based on PD-L1 expression. Approximately 330 patients stratified by region (Asia vs non- Asia) will be randomized in a 1:1 ratio to receive either BSC + avelumab 10 mg/kg as a 1-hour intravenous infusion Q2W, or BSC + chemotherapy if eligible (physician's choice of irinotecan 150 mg/m2 Q2W or paclitaxel 80 mg/m2 weekly for 3 out of 4 weeks, in a 4-week treatment cycle); patients not eligible for chemotherapy will receive BSC only. Treatment is given until disease progression, unacceptable toxicity, or consent withdrawal. Trial enrollment began in December 2015. ∗Proposed INN.