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
| Original language | English |
|---|---|
| Article number | e000674 |
| Journal | Journal for ImmunoTherapy of Cancer |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 15.05.2020 |
Funding
The study was sponsored by Merck KGaA, Darmstadt, Germany, and is part of an alliance between Merck KGaA and Pfizer. Merck KGaA provided the study drug and worked with investigators on the trial design and plan, collection and analysis of data, and interpretation of results. Medical writing support was provided by ClinicalThinking and funded by Merck KGaA and Pfizer. SPD reports serving as a consultant or advisor for Amgen, EMD Serono (a business of Merck KGaA, Darmstadt, Germany), GlaxoSmithKline, Immunocore, Immune Design, Incyte, Merck & Co, and Nektar; has received research grants from Amgen, Bristol Myers Squibb, Deciphera, EMD Serono, Incyte, Merck & Co, and Nektar; and has received reimbursement for travel and accommodation expenses from Adaptimmune, EMD Serono, Immunocore and Nektar. SB has received honoraria from and served as a consultant or advisor for Bristol Myers Squibb, EMD Serono, Genentech/Roche, and Sanofi/Regeneron; has received institutional research funding from Bristol Myers Squibb, EMD Serono, Exicure, Immune Design, Merck & Co, NantKwest, Novartis, and OncoSec; and has received reimbursement for travel and accommodation expenses from NantKwest. ASB reports serving as a consultant or advisor for Bayer, Deciphera, EMD Serono, and PierianDx. OH reports serving as a consultant or advisor for Amgen, Bristol Myers Squibb, Merck & Co, Novartis, and Roche; has received honoraria from Amgen, Array BioPharma, Bristol Myers Squibb, Genentech/Roche, Novartis, and Sanofi/Regeneron; is a member of a speakers bureau for Amgen, Array BioPharma, Bristol Myers Squibb, Genentech, Novartis, and Sanofi/Regeneron; and has received institutional research funding from Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Celldex, CytomX Therapeutics, Genentech, GlaxoSmithKline, Immunocore, Incyte, Iovance Biotherapeutics, MedImmune, Merck & Co, Merck Serono, Novartis, Parker Institute for Cancer Immunotherapy, Pfizer, Polynoma, Regeneron, and Roche. JMM has received honoraria from EMD Serono and Pfizer; reports serving as a consultant or advisor for Amgen, Array BioPharma, and Boehringer Ingelheim; has received institutional research funding from Amgen, AstraZeneca, Immunocore, Incyte, MacroGenics, Merck & Co, Novartis, Polynoma, and Sanofi; has received reimbursement for travel and accommodation expenses from EMD Serono and Merck & Co; and has other relationships with Amgen, Array BioPharma, Boehringer Ingelheim, EMD Serono, and Merck & Co. PT has received speakers honoraria from Bristol Myers Squibb, CureVac, Merck & Co, Novartis, Pierre Fabre, and Roche; reports serving as a consultant or advisor for Bristol Myers Squibb, Merck KGaA, Novartis, Pierre Fabre, Sanofi, and Roche; and has received travel support from Bristol Myers Squibb and Pierre Fabre. CL has received honoraria from Amgen, Bristol Myers Squibb, Incyte, Merck & Co, Novartis, Pfizer, Pierre Fabre, and Roche; reports serving as a consultant or advisor for Amgen, Bristol Myers Squibb, Merck & Co, Novartis, and Roche; is a member of a speakers bureau for Amgen, Bristol Myers Squibb, Novartis, and Roche; has received research funding from Bristol Myers Squibb and Roche; has received reimbursement for travel and accommodation expenses from Bristol Myers Squibb; and has other relationships with Avantis Medical Systems. KDL has received honoraria from Array BioPharma and Incyte; has served as a consultant or advisor for Array BioPharma, Merck KGaA, Regeneron, and Roche; and has received research funding from Array BioPharma, Bristol Myers Squibb, Incyte, Iovance Biotherapeutics, Merck KGaA, Nektar, and Roche/Genentech. MM has served as a consultant or advisor for Pfizer and Novartis and has received reimbursement for travel and accommodation expenses from Novartis. SG reports employment at EMD Serono Research & Development Institute; a business of Merck KGaA. PS reports employment at EMD Serono Research & Development Institute; a business of Merck KGaA. BE-L reports employment at Merck KGaA. MB reports employment at EMD Serono Research & Development Institute; a business of Merck KGaA. GG reports employment at Merck KGaA. PTN has received honoraria from EMD Serono and Merck & Co; reports serving as a consultant or advisor for EMD Serono and Pfizer; has received research funding from Bristol Myers Squibb and EMD Serono; and reports a pending patent for high-affinity T-cell receptors that target the Merkel cell polyomavirus. KCS, IB and GPL declare that they have no competing interests.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
