Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced unresectable mesothelioma from the JAVELIN solid tumor phase Ib trial: Safety, clinical activity, and PD-L1 expression.

8503 Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab in patients (pts) with unresectable mesothelioma (NCT01772004). Methods: Pts with unresectable pleural or peritoneal mesothelioma, progressed after a platinum-pemetrexed-containing regimen and unselected for PD-L1 expression, were treated with avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1). Objective response rate (ORR) 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, 53 pts were treated with avelumab and followed for a median of 46 wks (range 11-59). Median age was 66 y (range 32-84), ECOG PS was 0 (26.4%) or 1 (73.6%), median number of prior treatments was 1.5 (range 0-7). Histology was epithelial (81.1%), mixed (11.3%), sarcomatoid (3.8%), or unknown (3.8%). Treatment-related (TR) AEs occurred in 41 pts (77.4%); most common (>10%) were infusion-related reaction (20 [37.7%]), fatigue (8 [15.1%]), chills (8 [15.1%]), and pyrexia (6 [11.3%]), all of grade 1/2. Grade ≥3 TRAEs occurred in 4 pts (7.5%; colitis, decreased lymphocytes, and increased GGT or CPK [each 1 event]); there were no treatment-related deaths. Unconfirmed ORR was 9.4% (5 PRs; 95% CI: 3.1, 20.7); 4 were ongoing. Stable disease was observed in 25 pts (47.2%); disease control rate was 56.6%. Median PFS was 17.1 wks (95% CI: 6.1, 30.1), and PFS rate at 24 wks was 38.4% (95% CI: 23.3, 53.4). Using a ≥5% cutoff for tumor cell staining, 14/39 evaluable (35.9%) were PD-L1+, ORR was 14.3% in PD-L1+ (2/14) vs 8.0% in PD-L1– pts (2/25), and median PFS was 17.1 wks (95% CI: 5.4, ne) in PD-L1+ vs 7.4 wks (95% CI: 6.0, 30.1) in PD-L1− pts. Conclusions: Avelumab showed an acceptable safety profile and clinical activity in PD-L1+ and PD-L1− pts with advanced unresectable mesothelioma, a dataset representing the largest study to date of an all-comer population in this tumor type treated with anti-PD-(L)1. *Proposed INN. Clinical trial information: NCT01772004.