• Raffit Hassan, Anish Thomas, John J Nemunaitis, Manish R Patel, Jaafar Bennouna, Franklin L Chen, Jean-Pierre Delord, Afshin Dowlati, Samith T Kochuparambil, Matthew H Taylor, John D Powderly, Ulka N Vaishampayan, Claire Verschraegen, Hans Juergen Grote, Anja von Heydebreck, Kevin Chin, and James L Gulley.
• Thoracic and GI Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
• JAMA Oncol. 2019 Mar 1; 5 (3): 351-357.

ImportancePatients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti-programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti-programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma.ObjectiveTo assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma.Design, Setting, And ParticipantsPhase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015.InterventionsParticipants received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study.Main Outcomes And MeasuresPrespecified end points included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression-based analyses; and safety.ResultsOf 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60%) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38%) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9% (5 patients; 95% CI, 3.1%-20.7%), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95% CI, 11.1 to not estimable months) and occurred in patients with PD-L1-positive tumors (3 of 16; ORR, 19%; 95% CI, 4.0%-45.6%) and PD-L1-negative tumors (2 of 27; ORR, 7%; 95% CI, 0.9%-24.3%) based on a 5% or greater PD-L1 cutoff. Disease control rate was 58% (31 patients). Median PFS was 4.1 (95% CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4% (95% CI, 7.7%-30.4%). Median OS was 10.7 (95% CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8% (95% CI, 29.8%-57.0%). Five patients (9%) had a grade 3 or 4 treatment-related adverse event, and 3 (6%) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths.Conclusions And RelevanceAvelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma.Trial RegistrationClinicalTrials.gov identifier: NCT01772004.

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