Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced gastric or gastroesophageal junction cancer from JAVELIN solid tumor phase Ib trial: Analysis of safety and clinical activity.

Abstract

4009 Background: Avelumab (proposed INN) is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab as a first-line maintenance (Mn) or second-line (2L) therapy in patients (pts) with advanced gastric or gastroesophageal junction cancer (GC/GEJ; NCT01772004), including activity associated with PD-L1 expression. Methods: Pts with GC/GEJ received avelumab at 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Response was 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 IHC. Results: As of Oct 23 2015, 151 pts were treated with avelumab (62 pts, 2L; 89 pts, Mn) and followed for median of 49 wks (range 9-84). Treatment-related adverse events (TRAEs) of any grade occurred in 89 pts (58.9%); most common ( > 10%) were infusion-related reaction (19 [12.6%]) and fatigue (16 [10.6%]). Grade ≥ 3 TRAEs were reported in 15 pts (9.9%); fatigue, asthenia, increased GGT, thrombocytopenia, and anemia occurred in > 1 pt (2 each; 1.3%). There was 1 treatment-related death (hepatic failure/autoimmune hepatitis). Fourteen pts had an unconfirmed response: 2L 6/62 (9.7%), all PRs; Mn 8/89 (9.0%), 2 CRs, 6 PRs. In 2L and Mn pts, disease control rate was 29.0% and 57.3%, and median PFS was 6.0 wks (95% CI: 5.7, 6.4) and 12.0 wks (95% CI: 9.9, 17.6), respectively. PD-L1 expression was evaluable in 74 pts (22/62 2L, 52/89 Mn). Activity based on a ≥ 1% cutoff for tumor cell staining is shown in the table. Conclusions: Single-agent avelumab had an acceptable safety profile and promising clinical activity in unselected pts with GC/GEJ treated in Mn and 2L settings. These data represent the largest study of anti-PD-(L)1 agents in GC/GEJ. Two randomized phase III trials of avelumab in GC are open. Clinical trial information: NCT01772004. 2L (n = 22) Mn (n = 52) PD-L1+ (n = 11) PD-L1− (n = 11) PD-L1+ (n = 20) PD-L1− (n = 32) ORR, % (95% CI) 18.2 (2.3, 51.8) 9.1 (0.2, 41.3) 10.0 (1.2, 31.7) 3.1 (0.1, 16.2) Median PFS, wks (95% CI) 6.3 (5.4, 18.0) 10.4 (4.1, 21.9) 17.6 (6.0, 24.1) 11.6 (5.7, 14.1)