MERKLIN2: Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
- 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
- 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)
Eligibility Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UZ Leuven | Leuven | Belgium | ||
| 2 | Bordeaux Hôpital Saint Andre | Bordeaux | France | ||
| 3 | Hôpital Ambroise Paré - Boulogne-Billancourt | Boulogne-Billancourt | France | ||
| 4 | CHU Nantes - Hotel Dieu | Nantes | France | ||
| 5 | Hôpital Saint-Louis | Paris | France | ||
| 6 | Universitätsklinikum Dresden | Dresden | Germany | ||
| 7 | Helios Klinikum Erfurt | Erfurt | Germany | ||
| 8 | Universitätsklinikum Essen | Essen | Germany | ||
| 9 | Universitätsklinikum Heidelberg | Heidelberg | Germany | ||
| 10 | Universitätsklinikum Schleswig-Holstein Kiel | Kiel | Germany | ||
| 11 | Universitätsklinikum Köln | Köln | Germany | ||
| 12 | Universitätsklinikum Leipzig | Leipzig | Germany | ||
| 13 | Universitätsklinikum Schleswig-Holstein, Campus Lübeck | Lübeck | Germany | ||
| 14 | Technische Universität München | München | Germany | ||
| 15 | Universitätsklinikum Tübingen | Tübingen | Germany | ||
| 16 | Instituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari | Bari | Italy | ||
| 17 | Istituto Nazionale Tumori Fondazione G.Pascale | Naples | Italy | ||
| 18 | IOV - Istituto Oncologico Veneto IRCCS | Padova | Italy | ||
| 19 | Fondazione del Piemonte per l'Oncologia | Torino | Italy | ||
| 20 | Netherlands Cancer Institute Amsterdam | Amsterdam | Netherlands | ||
| 21 | Academic Hospital Maastricht | Maastricht | Netherlands | ||
| 22 | Hospital Universitari Vall d'Hebron | Barcelona | Spain |
Sponsors and Collaborators
- 4SC AG
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 4SC-202-3-2018
- 2018-004788-30