Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1
- Conditions
- Merkel Cell Carcinoma
- Interventions
- Registration Number
- NCT04393753
- Lead Sponsor
- 4SC AG
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description domatinostat and avelumab domatinostat in combination with avelumab Single arm study of Domatinostat tablets in combination with avelumab infusion
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) up to 24 months Objective Response Rate (ORR) defined as the percentage of patients having a confirmed CR or PR according to RECIST v1.1
- Secondary Outcome Measures
Name Time Method Durable Response Rate (DRR) up to 24 months Durable Response Rate (DRR), defined as the percentage of patients having a RECIST v1.1 response lasting ≥ 6 months
Duration of Response (DoR) up to 24 months 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) up to 24 months 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) up to 24 months 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) up to 24 months 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
Overall Survival (OS) up to 36 months Overall Survival (OS), defined as the time from the first administration of study medication until death due to any cause
OS Rate up to 12 months OS Rate, defined as the percentage of patients alive at 6 and at 12 months after first administration of study drug
Progression Free Survival (PFS) up to 24 months 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 up to 24 months PFS Rate, defined as the percentage of patients without PD at 6 and 12 months after first administration of study drug
Safety and Tolerability up to 24 months 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) up to 24 months 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 up to 48 weeks Single trough values of domatinostat and avelumab at pre-defined time points
Avelumab anti-drug antibodies (ADA) up to 48 weeks Avelumab anti-drug antibodies (ADA)
Trial Locations
- Locations (22)
Netherlands Cancer Institute Amsterdam
🇳🇱Amsterdam, Netherlands
Istituto Nazionale Tumori Fondazione G.Pascale
🇮🇹Naples, Italy
IOV - Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Italy
Bordeaux Hôpital Saint Andre
🇫🇷Bordeaux, France
CHU Nantes - Hotel Dieu
🇫🇷Nantes, France
Hôpital Ambroise Paré - Boulogne-Billancourt
🇫🇷Boulogne-Billancourt, France
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
UZ Leuven
🇧🇪Leuven, Belgium
Universitätsklinikum Dresden
🇩🇪Dresden, Germany
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Hôpital Saint-Louis
🇫🇷Paris, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Germany
Instituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
🇮🇹Bari, Italy
Technische Universität München
🇩🇪München, Germany
Universitätsklinikum Köln
🇩🇪Köln, Germany
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
🇩🇪Lübeck, Germany
Fondazione del Piemonte per l'Oncologia
🇮🇹Torino, Italy
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Academic Hospital Maastricht
🇳🇱Maastricht, Netherlands
Universitätsklinikum Schleswig-Holstein Kiel
🇩🇪Kiel, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany