Safety, PD-L1 expression, and clinical activity of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with advanced gastric or gastroesophageal junction cancer.

Abstract

167 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report safety and clinical activity of avelumab in patients (pts) with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) based on level of PD-L1 expression. This phase Ib JAVELIN study (NCT01772004) enrolled pts who had progressed on prior therapy ( ≥ 2L) and pts who had received 1L chemotherapy but had not yet progressed (switch-maintenance [Mn]) Methods: Pts received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumours were assessed every 6 wks (RECIST 1.1). Best overall response and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry using various cutoff criteria Results: As of Feb 13, 2015, 75 pts with GC/GEJ were treated with avelumab (20 pts, 2L; 55 pts, Mn). Treatment-related treatment-emergent AEs (TR-TEAEs) of any grade occurred in 47 pts (62.7%); the most common ( > 10%) was infusion-related reaction (12 [16.0%], all grade 1/2). Nine pts (12.0%) reported a grade ≥ 3 TR-TEAE, including fatigue (2), thrombocytopenia (2), and anemia (2; each 2.7%). There was 1 treatment-related death (hepatic failure/autoimmune hepatitis). Responses were observed in 7 pts (3/20 2L, all PRs; 4/55 Mn, 1 CR, 3 PRs). PD-L1 expression was evaluable in 55 pts (12/20 2L, 43/55 Mn), including in 3 pts with a response. Median PFS in 2L group was 36.0 wks (95% CI: 6.0, 36.0) for PD-L1+ and 11.6 wks (2.1, 21.9) for PD-L1− ( ≥ 1% cutoff). In Mn group, median PFS for PD-L1+ and PD-L1− status was 17.6 wks (5.9, 18.0) and 11.6 wks (5.7, 17.7), respectively ( ≥ 1% cutoff). Conclusions: Single agent avelumab showed an acceptable safety profile and clinical activity in GC/GEJ pts. Objective responses and disease stabilization were observed in both groups. Median PFS was longer in PD-L1+ pts. Phase III trials in 1L and 3L GC/GEJ are underway.*Proposed INN Clinical trial information: NCT01772004.