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Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1 (MERKLIN2)

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ClinicalTrials.gov Identifier: NCT04393753
Recruitment Status : Recruiting
First Posted : May 19, 2020
Last Update Posted : November 20, 2020
Sponsor:
Information provided by (Responsible Party):
4SC AG

Study Description
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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
Merkel Cell Carcinoma Drug: domatinostat in combination with avelumab Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 1, 2020
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arms and Interventions
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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
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Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 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 :
  1. Durable Response Rate (DRR) [ Time Frame: up to 24 months ]
    Durable Response Rate (DRR), defined as the percentage of patients having a RECIST v1.1 response lasting ≥ 6 months

  2. Duration of Response (DoR) [ Time Frame: 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

  3. Disease Control Rate (DCR) [ Time Frame: 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.

  4. Durable Disease Control Rate (dDCR) [ Time Frame: 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

  5. Best Overall response (BOR) [ Time Frame: 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

  6. Progression Free Survival (PFS) [ Time Frame: 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)

  7. PFS Rate [ Time Frame: 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

  8. Overall Survival (OS) [ Time Frame: up to 36 months ]
    Overall Survival (OS), defined as the time from the first administration of study medication until death due to any cause

  9. OS Rate [ Time Frame: 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

  10. Safety and Tolerability [ Time Frame: 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)

  11. Health related Quality of Life (HrQoL) [ Time Frame: 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.

  12. Plasma concentration of domatinostat and avelumab [ Time Frame: up to 48 weeks ]
    Single trough values of domatinostat and avelumab at pre-defined time points

  13. Avelumab anti-drug antibodies (ADA) [ Time Frame: up to 48 weeks ]
    Avelumab anti-drug antibodies (ADA)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04393753


Contacts
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Contact: Chief Medical Officer +49 (0)89 700 7630 medical.request@4sc.com

Locations
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Sponsors and Collaborators
4SC AG
More Information
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Responsible Party: 4SC AG
ClinicalTrials.gov Identifier: NCT04393753    
Other Study ID Numbers: 4SC-202-3-2018
2018-004788-30 ( EudraCT Number )
First Posted: May 19, 2020    Key Record Dates
Last Update Posted: November 20, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
 Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue