First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study

August 10, 2021


Journal for Immunotherapy of Cancer

Publication Date

August 10, 2021


D'Angelo SP, Lebbé C, Mortier L, Brohl AS, Fazio N, Grob JJ, Prinzi N, Hanna GJ, Hassel JC, Kiecker F, Georges S, Ellers-Lenz B, Shah P, Güzel G, Nghiem P

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This study provides evidence of frequent and durable responses to avelumab (anti-PD-L1) when patients receive such immune stimulation before starting traditional chemotherapy.


Background: Avelumab (anti-programmed death ligand 1 (PD-L1)) is approved in multiple countries for the treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. We report efficacy and safety data and exploratory biomarker analyses from a cohort of patients with mMCC treated with first-line avelumab in a phase II trial.

Methods: Patients with treatment-naive mMCC received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was durable response, defined as objective response (complete or partial response; assessed by independent review) lasting ≥6 months. Additional assessments included progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses.

Results: In 116 patients treated with avelumab, median follow-up was 21.2 months (range: 14.9-36.6). Thirty-five patients had a response lasting ≥6 months, giving a durable response rate of 30.2% (95% CI: 22.0% to 39.4%). The objective response rate was 39.7% (95% CI: 30.7% to 49.2%). Median PFS was 4.1 months (95% CI: 1.4 to 6.1) and median OS was 20.3 months (95% CI: 12.4 to not estimable). Response rates were numerically higher in patients with PD-L1+ tumors, Merkel cell polyomavirus (MCPyV)-negative tumors, and tumors with increased intratumoral CD8+ T-cell density. Exploratory analyses did not identify a biomarker that could reliably predict a response to first-line treatment with avelumab; however, a novel gene expression signature to identify the presence of MCPyV+ tumors was derived. Treatment-related adverse events (any grade) occurred in 94 (81.0%) patients, including grade 3/4 events in 21 (18.1%) patients; no treatment-related deaths occurred.

Conclusion: In patients with mMCC, first-line treatment with avelumab led to responses in 40% and durable responses in 30%, and was associated with a low rate of grade 3/4 treatment-related adverse events.

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