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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Merkel Cell Carcinoma

Intervention / Treatment
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* Drug: domatinostat in combination with avelumab


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: domatinostat and avelumab<br>Single arm study of Domatinostat tablets in combination with avelumab infusion | Drug: domatinostat in combination with avelumab<br>* domatinostat tablets and avelumab infusion<br>|

What is the study measuring?
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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 |