Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti-programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab. METHODS: In a cohort of this single-arm, phase 2 trial (JAVELIN Merkel 200), patients with mMCC and disease progression after prior chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent review per Response Evaluation Criteria in Solid Tumors V.1.1. Other assessments included duration of response, progression-free survival, overall survival (OS), safety and biomarker analyses. RESULTS: As of 14 September 2018, 88 patients had been followed up for a median of 40.8 months (range 36.4-49.7 months). The ORR was 33.0% (95% CI 23.3% to 43.8%), including a complete response in 11.4% (10 patients), and the median duration of response was 40.5 months (95% CI 18.0 months to not estimable). As of 2 May 2019 (≥44 months of follow-up), the median OS was 12.6 months (95% CI 7.5 to 17.1 months) and the 42-month OS rate was 31% (95% CI 22% to 41%). Of long-term survivors (OS >36 months) evaluable for PD-L1 expression status (n=22), 81.8% had PD-L1+ tumors. In exploratory biomarker analyses, high tumor mutational burden (≥2 non-synonymous somatic variants per megabase) and high major histocompatibility complex class I expression (30% of tumors with highest expression) were associated with trends for improved ORR and OS. In long-term safety assessments (≥36 months of follow-up), no new or unexpected adverse events were reported, and no treatment-related deaths occurred. CONCLUSIONS: Avelumab showed continued durable responses and meaningful long-term survival outcomes in patients with mMCC, reinforcing avelumab as a standard-of-care treatment option for this disease. TRIAL REGISTRATION NUMBER: NCT02155647.

authors

  • D'Angelo, Sandra
  • Bhatia, Shailender
  • Brohl, Andrew S
  • Hamid, Omid
  • Mehnert, Janice M
  • Terheyden, Patrick
  • Shih, Kent C
  • Brownell, Isaac
  • Lebbé, Celeste
  • Lewis, Karl D
  • Linette, Gerald P
  • Milella, Michele
  • Georges, Sara
  • Shah, Parantu
  • Ellers-Lenz, Barbara
  • Bajars, Marcis
  • Güzel, Gülseren
  • Nghiem, Paul T

publication date

  • May 1, 2020

Research

keywords

  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Carcinoma, Merkel Cell
  • Immune Checkpoint Inhibitors
  • Skin Neoplasms

Identity

PubMed Central ID

  • PMC7239697

Scopus Document Identifier

  • 85084786425

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-14-2607

PubMed ID

  • 32414862

Additional Document Info

volume

  • 8

issue

  • 1