Abstract 1153TiP
Background
Merkel cell carcinoma (MCC) is a rare but highly aggressive human skin cancer that is often caused by the Merkel cell polyomavirus or extended exposure to sunlight. Historically, first-line treatment options for patients with advanced unresectable/metastatic MCC have been rare. However, 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 to previous anti-PD-(L)1 antibody monotherapy ultimately leaving these patients with only limited treatment options. Recent preclinical data suggest that the small molecule selective class I histone deacetylase inhibitor (HDACi) domatinostat is able to overcome critical mechanisms of MCC resistance to checkpoint inhibitors. These escape mechanisms include the epigenetic downregulation of the antigen processing and presentation machinery, hence treatment with domatinostat is thought to favorably modulate the tumor environment therefore allowing a reintroduction of anti-PD-(L)1 therapy for an improved and sustained clinical benefit.
Trial design
The study 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 advanced unresectable/metastatic MCC that are progressing on previous anti-PD-(L)1 therapy. A total of 40 patients will be enrolled in up to 40 clinical study sites in Europe and USA. Anti-tumor activity will be primarily assessed by the Objective Response Rate (ORR) defined as the percentage of patients having a confirmed CR or PR according to RECIST v1.1 in an exploratory analysis. Secondary objectives include additional efficacy assessments, safety, quality of life (HRQoL) and pharmacokinetics of domatinostat in combination with avelumab. Correlative aims include evaluating biomarkers for association with clinical benefit.
Clinical trial identification
NCT04393753.
Editorial acknowledgement
Legal entity responsible for the study
4SC AG.
Funding
4SC AG.
Disclosure
A.C.J. van Akkooi: Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Bristol- Myers Squibb; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy: Merck KgAa/ Pfizer; Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (institution), Advisory/Consultancy: 4SC AG; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Merck KGaA/ Pfizer. P.A. Ascierto: Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Array; Shareholder/Stockholder/Stock options: PrimeVax; Honoraria (self), Advisory/Consultancy: 4SC AG; Honoraria (self), Advisory/Consultancy: Immunocore; Honoraria (self), Advisory/Consultancy: Sandoz; Honoraria (self), Advisory/Consultancy: Ultimovacs; Honoraria (self), Advisory/Consultancy: Idera; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Sun Pharma; Honoraria (self), Advisory/Consultancy: Syndax; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MedImmune; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Newlinks Genetics; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy: Array; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Nektar; Honoraria (self), Advisory/Consultancy: Alkermes; Honoraria (self), Advisory/Consultancy: Italfarmaco; Travel/Accommodation/Expenses: Merck Sharp & Dohme. J.C. Becker: Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Merck KGaA; Speaker Bureau/Expert testimony: Recordati; Speaker Bureau/Expert testimony: Sanofi; Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: eTheRNA; Honoraria (institution), Advisory/Consultancy: In ProTher; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: 4SC AG; Honoraria (institution), Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Merck KgAa; Research grant/Funding (institution): HTG; Research grant/Funding (institution): IQVIA; Research grant/Funding (institution): Alcedis. P. Nathan: Honoraria (self), Advisory/Consultancy: 4SC; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Immunocore. P. Nghiem: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy: UpToDate; Advisory/Consultancy: 4SC AG; Research grant/Funding (self): EMD Serono; Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Amgen; Research grant/Funding (self): Kadmon; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Syndax; Research grant/Funding (self): Incyte; Research grant/Funding (self): AstraZeneca; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Genzyme & Regeneration; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Amgen. U. Ostermeier, P.G. Reimann, F. Hermann: Full/Part-time employment: 4SC AG.