Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1 (MERKLIN2)
Primary Purpose
Merkel Cell Carcinoma
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
domatinostat in combination with avelumab
Sponsored by
About this trial
This is an interventional treatment trial for Merkel Cell Carcinoma
Eligibility Criteria
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)
Sites / Locations
- UZ Leuven
- Bordeaux Hôpital Saint Andre
- Hôpital Ambroise Paré - Boulogne-Billancourt
- CHU Nantes - Hotel Dieu
- Hôpital Saint-Louis
- Universitätsklinikum Dresden
- Helios Klinikum Erfurt
- Universitätsklinikum Essen
- Universitätsklinikum Heidelberg
- Universitätsklinikum Schleswig-Holstein Kiel
- Universitätsklinikum Köln
- Universitätsklinikum Leipzig
- Universitätsklinikum Schleswig-Holstein, Campus Lübeck
- Technische Universität München
- Universitätsklinikum Tübingen
- Instituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
- Istituto Nazionale Tumori Fondazione G.Pascale
- IOV - Istituto Oncologico Veneto IRCCS
- Fondazione del Piemonte per l'Oncologia
- Netherlands Cancer Institute Amsterdam
- Academic Hospital Maastricht
- Hospital Universitari Vall d'Hebron
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
domatinostat and avelumab
Arm Description
Single arm study of Domatinostat tablets in combination with avelumab infusion
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Durable Response Rate (DRR)
Durable Response Rate (DRR), defined as the percentage of patients having a RECIST v1.1 response lasting ≥ 6 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
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.
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
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
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)
PFS Rate
PFS Rate, defined as the percentage of patients without PD at 6 and 12 months after first administration of study drug
Overall Survival (OS)
Overall Survival (OS), defined as the time from the first administration of study medication until death due to any cause
OS Rate
OS Rate, defined as the percentage of patients alive at 6 and at 12 months after first administration of study drug
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)
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.
Plasma concentration of domatinostat and avelumab
Single trough values of domatinostat and avelumab at pre-defined time points
Avelumab anti-drug antibodies (ADA)
Avelumab anti-drug antibodies (ADA)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04393753
Brief Title
Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
4SC AG
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Merkel Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
domatinostat and avelumab
Arm Type
Experimental
Arm Description
Single arm study of Domatinostat tablets in combination with avelumab infusion
Intervention Type
Drug
Intervention Name(s)
domatinostat in combination with avelumab
Intervention Description
domatinostat tablets and avelumab infusion
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Objective Response Rate (ORR) defined as the percentage of patients having a confirmed CR or PR according to RECIST v1.1
Time Frame
up to 24 months
Secondary Outcome Measure Information:
Title
Durable Response Rate (DRR)
Description
Durable Response Rate (DRR), defined as the percentage of patients having a RECIST v1.1 response lasting ≥ 6 months
Time Frame
up to 24 months
Title
Duration of Response (DoR)
Description
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
Time Frame
up to 24 months
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
up to 24 months
Title
Durable Disease Control Rate (dDCR)
Description
Durable Disease Control Rate (dDCR), defined as the percentage of patients having a RECIST v1.1 disease control lasting ≥ 6 months
Time Frame
up to 24 months
Title
Best Overall response (BOR)
Description
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
Time Frame
up to 24 months
Title
Progression Free Survival (PFS)
Description
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)
Time Frame
up to 24 months
Title
PFS Rate
Description
PFS Rate, defined as the percentage of patients without PD at 6 and 12 months after first administration of study drug
Time Frame
up to 24 months
Title
Overall Survival (OS)
Description
Overall Survival (OS), defined as the time from the first administration of study medication until death due to any cause
Time Frame
up to 36 months
Title
OS Rate
Description
OS Rate, defined as the percentage of patients alive at 6 and at 12 months after first administration of study drug
Time Frame
up to 12 months
Title
Safety and Tolerability
Description
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)
Time Frame
up to 24 months
Title
Health related Quality of Life (HrQoL)
Description
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.
Time Frame
up to 24 months
Title
Plasma concentration of domatinostat and avelumab
Description
Single trough values of domatinostat and avelumab at pre-defined time points
Time Frame
up to 48 weeks
Title
Avelumab anti-drug antibodies (ADA)
Description
Avelumab anti-drug antibodies (ADA)
Time Frame
up to 48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Facility Information:
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
Facility Name
Bordeaux Hôpital Saint Andre
City
Bordeaux
Country
France
Facility Name
Hôpital Ambroise Paré - Boulogne-Billancourt
City
Boulogne-Billancourt
Country
France
Facility Name
CHU Nantes - Hotel Dieu
City
Nantes
Country
France
Facility Name
Hôpital Saint-Louis
City
Paris
Country
France
Facility Name
Universitätsklinikum Dresden
City
Dresden
Country
Germany
Facility Name
Helios Klinikum Erfurt
City
Erfurt
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
Country
Germany
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein Kiel
City
Kiel
Country
Germany
Facility Name
Universitätsklinikum Köln
City
Köln
Country
Germany
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
City
Lübeck
Country
Germany
Facility Name
Technische Universität München
City
München
Country
Germany
Facility Name
Universitätsklinikum Tübingen
City
Tübingen
Country
Germany
Facility Name
Instituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
City
Bari
Country
Italy
Facility Name
Istituto Nazionale Tumori Fondazione G.Pascale
City
Naples
Country
Italy
Facility Name
IOV - Istituto Oncologico Veneto IRCCS
City
Padova
Country
Italy
Facility Name
Fondazione del Piemonte per l'Oncologia
City
Torino
Country
Italy
Facility Name
Netherlands Cancer Institute Amsterdam
City
Amsterdam
Country
Netherlands
Facility Name
Academic Hospital Maastricht
City
Maastricht
Country
Netherlands
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1
We'll reach out to this number within 24 hrs