Phase 1b Study Of Avelumab In Advanced Previously Treated Mesothelioma: Long-Term Follow-Up From Javelin Solid Tumor.

8563 Background: Avelumab, a human anti-PD-L1 IgG1 antibody, is approved for treatment of metastatic Merkel cell carcinoma in various countries and advanced urothelial carcinoma progressed on platinum therapy in the US. We report updated results with avelumab in a phase 1b cohort of patients (pts) with mesothelioma. Methods: Pts with unresectable pleural or peritoneal mesothelioma progressed after platinum and pemetrexed therapy received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). A post-hoc landmark analysis was performed using a Cox regression model. Results: At data cutoff on Dec 31, 2016, 53 pts were treated and followed for a median of 24.8 mo (range 16.8–27.8). Pts had received a median of 2 prior lines of therapy (range 1–8). Confirmed ORR was 9.4% (95% CI 3.1–20.7) including complete response (CR) in 1.9% and partial response (PR) in 7.5%. Median duration of response was 15.2 mo (95% CI 11.1–not estimable). 26 pts (49.1%) had stable disease (SD) as best response and the disease control rate was 58.5%. Median PFS was 4.1 mo (95% CI 1.4–6.2) and the 6-mo PFS rate was 38.0% (95% CI 24.2–51.7). Median OS was 10.9 mo (95% CI 7.5–21.0) and the 12-mo OS rate was 45.9% (95% CI 31.9–58.8). In a landmark analysis of pts still on treatment at 3 mo, duration of OS beyond 3 mo was longer in patients who had achieved CR/PR (HR < 0.01; 95% CI 0–inf.) or SD (HR 0.43; 95% CI 0.20–0.89) vs other pts. In evaluable pts with PD-L1+ (n = 16) or PD-L1− (n = 27) tumors (≥5% tumor cell cutoff), ORR was 18.8% (95% CI 4.0–45.6) and 7.4% (95% CI 0.9–24.3), respectively. Treatment-related (TR)AEs occurred in 43 pts (81.1%), including infusion-related reaction (35.8%; all grade 1/2), chills (15.1%), fatigue (15.1%), and pyrexia (11.3%) in > 10%. 5 pts (9.4%) had a grade ≥3 TRAE. 12 pts (22.6%) had an immune-related TRAE, which was grade ≥3 in 3 pts (5.7%; pneumonitis, colitis, and type 1 diabetes mellitus). No treatment-related deaths occurred. Conclusions: Updated data confirm the clinical activity and acceptable safety of avelumab in pts with previously treated mesothelioma. Clinical trial information: NCT01772004.