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

Abstract

BackgroundAvelumab (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.MethodsPatients 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.ResultsIn 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.ConclusionIn 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.

Avelumab in patients with previously treated metastatic Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after >5 years of follow-up

“…In 2017, avelumab became the first approved treatment for patients with mMCC on the basis of results from the phase II JAVELIN Merkel 200 trial, which investigated avelumab monotherapy in patients with mMCC in two cohorts: as second-line or later treatment in patients who had disease progression after one or more lines of chemotherapy (Part A) and as first-line treatment (Part B). 6 , 7 In Part A ( N = 88), after ≥3 years of follow-up, the objective response rate (ORR) was 33.0%, including a complete response in 11.4% of patients. 8 Median OS after ≥44 months of follow-up was 12.6 months, and the 42-month OS rate was 31%.…”

A Challenging Nodular Lesion of the Ear

“…Exciting new class of drugs, including checkpoint inhibitor immunotherapies, are giving promising results. In particular, those obtained with target therapy agents such as Avelumab (anti-PDL1 antibody) [10] may offer a glimmer of hope to these unlucky patients. New trials on combination therapies have to be conducted.…”

Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021

“…There was a trend for a higher response rate in patients with a high versus low tumor mutational burden (TMB), with the highest ORRs in the high TMB subgroup in patients with tumors that were also PD-L1-positive or MCPyV-negative [ 65 ]. First-line treatment with avelumab has also been associated with good responses; in 116 treatment-naïve patients treated with avelumab, the ORR was 39.7% and the durable response rate was 30.2% [ 67 ]. Avelumab was also associated with a clinically meaningful survival benefit in this cohort.…”