Clinical Trials /

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

NCT04393753

Description:

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

Related Conditions:
  • Merkel Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 4SC-202-3-2018
  • SECONDARY ID: 2018-004788-30
  • NCT ID: NCT04393753

Conditions

  • Merkel Cell Carcinoma

Interventions

DrugSynonymsArms
domatinostat in combination with avelumabdomatinostat and avelumab

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
domatinostat and avelumabExperimentalSingle arm study of Domatinostat tablets in combination with avelumab infusion
  • domatinostat in combination with avelumab

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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:up to 24 months
Safety Issue:
Description:Objective Response Rate (ORR) defined as the percentage of patients having a confirmed CR or PR according to RECIST v1.1

Secondary Outcome Measures

Measure:Durable Response Rate (DRR)
Time Frame:up to 24 months
Safety Issue:
Description:Durable Response Rate (DRR), defined as the percentage of patients having a RECIST v1.1 response lasting ≥ 6 months
Measure:Duration of Response (DoR)
Time Frame:up to 24 months
Safety Issue:
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
Measure:Disease Control Rate (DCR)
Time Frame:up to 24 months
Safety Issue:
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.
Measure:Durable Disease Control Rate (dDCR)
Time Frame:up to 24 months
Safety Issue:
Description:Durable Disease Control Rate (dDCR), defined as the percentage of patients having a RECIST v1.1 disease control lasting ≥ 6 months
Measure:Best Overall response (BOR)
Time Frame:up to 24 months
Safety Issue:
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
Measure:Progression Free Survival (PFS)
Time Frame:up to 24 months
Safety Issue:
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)
Measure:PFS Rate
Time Frame:up to 24 months
Safety Issue:
Description:PFS Rate, defined as the percentage of patients without PD at 6 and 12 months after first administration of study drug
Measure:Overall Survival (OS)
Time Frame:up to 36 months
Safety Issue:
Description:Overall Survival (OS), defined as the time from the first administration of study medication until death due to any cause
Measure:OS Rate
Time Frame:up to 12 months
Safety Issue:
Description:OS Rate, defined as the percentage of patients alive at 6 and at 12 months after first administration of study drug
Measure:Safety and Tolerability
Time Frame:up to 24 months
Safety Issue:
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)
Measure:Health related Quality of Life (HrQoL)
Time Frame:up to 24 months
Safety Issue:
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.
Measure:Plasma concentration of domatinostat and avelumab
Time Frame:up to 48 weeks
Safety Issue:
Description:Single trough values of domatinostat and avelumab at pre-defined time points
Measure:Avelumab anti-drug antibodies (ADA)
Time Frame:up to 48 weeks
Safety Issue:
Description:Avelumab anti-drug antibodies (ADA)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:4SC AG

Last Updated

September 23, 2020