Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1 (MERKLIN2)

A Phase II, Open Label Study to Investigate the Efficacy and Safety of Domatinostat in Combination With Avelumab in Patients With Advanced Unresectable/Metastatic Merkel Cell Carcinoma Progressing on Anti-PD-(L)1 Antibody Therapy

This phase II trial studies how well domatinostat (4SC-202) works in combination with avelumab in adult patients with advanced unresectable and/or metastatic Merkel Cell Carcinoma that have progressed on a previous therapy with an anti-PD-(L)1 antibody

Study Overview

• Status: Completed
• Conditions: Merkel Cell Carcinoma
• Intervention / Treatment: Drug: domatinostat in combination with avelumab

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • UZ Leuven
• France
  • Bordeaux, France
    • Bordeaux Hôpital Saint Andre
  • Boulogne-Billancourt, France
    • Hôpital Ambroise Paré - Boulogne-Billancourt
  • Nantes, France
    • CHU NANTES - Hôtel Dieu
  • Paris, France
    • Hopital Saint-Louis
• Germany
  • Dresden, Germany
    • Universitätsklinikum Dresden
  • Erfurt, Germany
    • HELIOS Klinikum Erfurt
  • Essen, Germany
    • Universitätsklinikum Essen
  • Heidelberg, Germany
    • Universitätsklinikum Heidelberg
  • Kiel, Germany
    • Universitätsklinikum Schleswig-Holstein Kiel
  • Köln, Germany
    • Universitatsklinikum Koln
  • Leipzig, Germany
    • Universitätsklinikum Leipzig
  • Lübeck, Germany
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • München, Germany
    • Technische Universität München
  • Tübingen, Germany
    • Universitatsklinikum Tubingen
• Italy
  • Bari, Italy
    • Instituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
  • Naples, Italy
    • Istituto Nazionale Tumori Fondazione G.Pascale
  • Padova, Italy
    • Iov - Istituto Oncologico Veneto Irccs
  • Torino, Italy
    • Fondazione del Piemonte per l'Oncologia
• Netherlands
  • Amsterdam, Netherlands
    • Netherlands Cancer Institute Amsterdam
  • Maastricht, Netherlands
    • Academic Hospital Maastricht
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed Merkel Cell Carcinoma (MCC)
• ECOG performance status ≤ 1
• MCC in an advanced, unresectable stage III or metastatic stage IV (includes patients who refused surgical resection or are not eligible for such surgical resection)
• Progressing on previous anti-PD-(L)1 antibody monotherapy within the last 12 weeks before planned first administration of study medication

Exclusion Criteria:

• History of serious anti-PD-(L)1 therapy-related adverse reactions prohibiting further avelumab treatment
• More than one line of previous systemic anti-neoplastic therapy other than anti-PD-(L)1 antibody monotherapy
• Palliative radiation therapy of single lesions within 2 weeks before planned administration of study medication
• Presence of significant active or chronic disease (infections, immunodeficiencies, cardiovascular, psychiatric disorders)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: domatinostat and avelumab; Single arm study of Domatinostat tablets in combination with avelumab infusion	Drug: domatinostat in combination with avelumab; domatinostat tablets and avelumab infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) defined as the percentage of patients having a confirmed CR or PR according to RECIST v1.1	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Durable Response Rate (DRR)	Durable Response Rate (DRR), defined as the percentage of patients having a RECIST v1.1 response lasting ≥ 6 months	up to 24 months
Duration of Response (DoR)	Duration of Response (DoR), defined as the time from an initial objective response (CR or PR) according to RECIST v1.1 until disease progression or death due to any cause	up to 24 months
Disease Control Rate (DCR)	Disease Control Rate (DCR), defined as the proportion of patients with either an objective response (CR, PR) or stable disease (SD) according to RECIST v1.1.	up to 24 months
Durable Disease Control Rate (dDCR)	Durable Disease Control Rate (dDCR), defined as the percentage of patients having a RECIST v1.1 disease control lasting ≥ 6 months	up to 24 months
Best Overall response (BOR)	Best Overall response (BOR), defined as the best response (PD, SD, PR, CR) according to RECIST v1.1 over the course of a patient's participation in the study, assessed up to 2 years	up to 24 months
Progression Free Survival (PFS)	Progression Free Survival (PFS), defined as the time from first dosing (Day +1) to the date of PD or death from any cause (whichever comes first)	up to 24 months
PFS Rate	PFS Rate, defined as the percentage of patients without PD at 6 and 12 months after first administration of study drug	up to 24 months
Overall Survival (OS)	Overall Survival (OS), defined as the time from the first administration of study medication until death due to any cause	up to 36 months
OS Rate	OS Rate, defined as the percentage of patients alive at 6 and at 12 months after first administration of study drug	up to 12 months
Safety and Tolerability	Safety and Tolerability of the study medication (determined by number, frequency, duration and severity of AEs using CTCAE v5.0, physical examination, laboratory tests, vital signs, and ECGs)	up to 24 months
Health related Quality of Life (HrQoL)	The impact of treatment on the patient's QoLwill be assessed with the questionnaires "Functional Assessment of Cancer Therapy - Melanoma (FACT-M)" where QoL is assessed on a scale 0-240 (higher score means better status of health), with "EQ-5D-5L" which is a multi attribute utility instrument for measuring health-related QoL as EQ5D index with a score 0-1 (higher score means better status of health) and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) with a score 0-100 per subscale (n=9 per item (n=6), higher score means better QoL.	up to 24 months
Plasma concentration of domatinostat and avelumab	Single trough values of domatinostat and avelumab at pre-defined time points	up to 48 weeks
Avelumab anti-drug antibodies (ADA)	Avelumab anti-drug antibodies (ADA)	up to 48 weeks

Collaborators and Investigators

• Sponsor: 4SC AG

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Actual): February 26, 2024
• Study Completion (Actual): February 26, 2024

Study Registration Dates

• First Submitted: May 12, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma, Neuroendocrine; Carcinoma; Carcinoma, Merkel Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: 4SC-202-3-2018; 2018-004788-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No