Abstract 1090TiP
Background
Merkel cell carcinoma (MCC) is a rare and highly aggressive human skin cancer often caused by the Merkel cell polyomavirus or extended exposure to sunlight. Since the approvals of avelumab globally and subsequently pembrolizumab (US only), anti-PD-(L)1 antibody therapies have become standard of care for MCC patients in recent years. Despite these successes, a significant proportion of MCC patients do not respond or relapse on such monotherapy and have an unmet medical need for a more effective first-line therapy. Preclinical data suggest that the small molecule selective class I histone deacetylase inhibitor (HDACi) domatinostat addresses critical, well-described escape mechanisms of MCC. These escape mechanisms include the epigenetic downregulation of the antigen processing and presentation machinery leading to an insufficient recognition of tumor cells by the immune system. Treatment with domatinostat is hypothesized to favorably modulate the tumor environment and synergize with anti-PD-L1 therapy for a higher response rate, deeper responses, and longer duration of response.
Trial design
MERKLIN 1 (NCT04874831) is a phase II, multicenter, single arm clinical trial of the orally administered HDACi domatinostat in combination with the anti-PD-L1 antibody avelumab for patients with treatment-naïve metastatic MCC. A total of 100 patients will be enrolled in up to 40 clinical study sites initially in Europe. The primary objective is to evaluate the clinical efficacy of the combination in treatment-naïve metastatic or distally recurrent MCC patients as determined by the objective response rate, defined as the percentage of patients having a confirmed complete response or partial response according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) by independent review. Secondary objectives include additional efficacy assessments, safety, health related quality of life and pharmacokinetics of domatinostat and avelumab. Correlative aims include evaluating biomarkers for association with clinical benefit.
Clinical trial identification
4SC-202-4-2019 (Protocol Number), EudraCT 2019-003575-19.
Editorial acknowledgement
Legal entity responsible for the study
4SC AG, collaborator Merck KG.
Funding
4SC AG.
Disclosure
F. Hermann: Financial Interests, Personal, Full or part-time Employment: 4SC AG. J. Henneberg: Financial Interests, Personal, Full or part-time Employment: 4SC AG. All other authors have declared no conflicts of interest.