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Clinical Trial
. 2019 Mar 1;5(3):351-357.
doi: 10.1001/jamaoncol.2018.5428.

Efficacy and Safety of Avelumab Treatment in Patients With Advanced Unresectable Mesothelioma: Phase 1b Results From the JAVELIN Solid Tumor Trial

Raffit Hassan  1 , Anish Thomas  2 , John J Nemunaitis  3 , Manish R Patel  4 , Jaafar Bennouna  5 , Franklin L Chen  6 , Jean-Pierre Delord  7 , Afshin Dowlati  8 , Samith T Kochuparambil  9 , Matthew H Taylor  10 , John D Powderly  11 , Ulka N Vaishampayan  12 , Claire Verschraegen  13 , Hans Juergen Grote  14 , Anja von Heydebreck  14 , Kevin Chin  15 , James L Gulley  16   17
Affiliations
Clinical Trial

Efficacy and Safety of Avelumab Treatment in Patients With Advanced Unresectable Mesothelioma: Phase 1b Results From the JAVELIN Solid Tumor Trial

Raffit Hassan et al. JAMA Oncol. .

Abstract

Importance: Patients 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.

Objective: To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma.

Design, setting, and participants: Phase 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.

Interventions: Participants received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study.

Main outcomes and measures: Prespecified 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.

Results: Of 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 relevance: Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma.

Trial registration: ClinicalTrials.gov identifier: NCT01772004.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hassan reported receiving research funding from Aduro Biotech, Bayer, and Morphotek. Dr Nemunaitis reported receiving consulting, advisory, and speaking fees from Amgen, AstraZeneca, and Symvivo; being a founder and member of the board of directors at Gradalis and serving as the Director of the phase 1 research program for US Oncology (USON); receiving compensation for expert testimony from Foundation Medicine; serving in a leadership role for Symvivo; receiving speaking fees from Amgen and AstraZeneca; receiving research funding, having stock or other ownership, patents, royalties, and other intellectual property from Gradalis; and receiving travel, accommodation, and expenses from Symvivo, Gradalis, Amgen, and AstraZeneca. Dr Patel reported receiving speaking fees from Celgene, Exelixis, Genentech/Roche, and Taiho Pharmaceutical. Dr Bennouna reported receiving consulting and advisory fees, honoraria, and speaking fees from AstraZeneca, Bristol-Meyers Squibb, Boehringer, Merck, and Roche; research funding from AstraZeneca and Merck KGaA; and travel, accommodation, and expenses from AstraZeneca and Roche. Dr Chen reported receiving honoraria from Celgene. Dr Dowlati reported receiving fees for consulting and advisory roles for AbbVie/Stemcentrx and ARIAD and research funding from Amgen, Bristol-Meyer Squibb, EMD Serono, Lilly/ImClone, MedImmune, and OncoMed. Dr Taylor reported receiving consulting and advisory fees and honoraria from Blueprint, Bristol-Myers Squibb, Eisai, Loxo, and Novartis; speaking fees from Bristol-Myers Squibb and Eisai; and travel, accommodation, and expenses from Blueprint, Bristol-Myers Squibb, Eisai, and Loxo. Dr Powderly reported receiving consulting and advisory fees from AstraZeneca/MedImmune, Bristol-Myers Squibb, Curis, Genentech/Roche, and TopAlliance BioSciences; serving in leadership roles for BioCytics and Carolina BioOncology Instititute; receiving speaking fees from Bristol-Myers Squibb, Dendreon, Genentech/Roche, and Merck; patents, royalties, and other intellectual property from Biocytics; stocks and other ownership interests in BioCytics, Bluebird Bio, Carolina BioOncology Institute, Juno Therapeutics, Kite Pharma, Lion Biotechnologies, and ZIOPHARM Oncology; and research funding from AbbVie, AstraZeneca, Bristol-Myers Squibb, Corvus Pharmaceuticals, Curis, EMD Serono, Genentech/Roche, Incyte, Lilly/ImClone, Macrogenics, Seattle Genetics, and TopAlliance BioSciences. Dr Vaishampayan reported receiving consulting and advisory fees from Astellas Pharma, Bayer, Bristol-Myers Squibb, Exelixis, Genentech/Roche, and Pfizer; honoraria from Bayer, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Janssen, Novartis, Pfizer, and Sanofi; speaking fees from Bayer, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Pfizer, and Sanofi; and research funding from Astellas Pharma, Bristol-Myers Squibb, Exelixis, Novartis, and Pfizer. Dr Gulley reported receiving research funding from Astellas Medivation, Bavarian Nordic, Celgene, EMD Serono, and Pfizer. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Profile
Figure 2.
Figure 2.. Kaplan-Meier Estimates of Progression-Free Survival (PFS) and Overall Survival (OS)
A, Progression-free survival (n = 53). B, Overall survival (n = 53).
See this image and copyright information in PMC

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