Merkel Cell Carcinoma
Conditions
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
Interventions
domatinostat tablets and avelumab infusion
Sponsors
4SC AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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) |
| 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 |
Countries
Belgium, France, Germany, Italy, Netherlands, Spain
Outcome results
None listed