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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04393753

Studienbeginn:
September 2020

Letztes Update:
20.11.2020

Wirkstoff:
domatinostat in combination with avelumab

Indikation (Clinical Trials):
Carcinoma, Merkel Cell, Carcinoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
4SC AG

Collaborator:
-

Kontakt

Studienlocations (3 von 45)

Alle anzeigen

Studien-Informationen

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

Ein-/Ausschlusskriterien

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)

Studien-Rationale

Primary outcome:

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:

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)

Geprüfte Regime

  • domatinostat in combination with avelumab:
    domatinostat tablets and avelumab infusion

Quelle: ClinicalTrials.gov


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