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

Merkel Cell Carcinoma Clinical Trial

— MERKLIN2  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04393753
• Other study ID #: 4SC-202-3-2018
• Secondary ID: 2018-004788-30
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 1, 2020
• Est. completion date: December 1, 2024

Study information

• Verified date: July 2023
• Source: 4SC AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: December 1, 2024
• Est. primary completion date: February 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Merkel Cell
• Merkel Cell Carcinoma

Intervention

Drug:
• domatinostat in combination with avelumab
domatinostat tablets and avelumab infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
4SC AG

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Plasma concentration of domatinostat and avelumab	Single trough values of domatinostat and avelumab at pre-defined time points	up to 48 weeks
Secondary	Avelumab anti-drug antibodies (ADA)	Avelumab anti-drug antibodies (ADA)	up to 48 weeks