Phase Ib/II Study of Carboplatin + M6620 + Avelumab in PARPi-resistant Ovarian Cancer

NCT ID: NCT03704467

Last Updated: 2020-11-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-04

Study Completion Date

2019-11-06

Brief Summary

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The study was to evaluate the efficacy and safety of avelumab in combination with M6620 + carboplatin in participants with PARPi-resistant, recurrent, platinum sensitive ovarian, primary peritoneal, or fallopian tube cancer.

Detailed Description

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The study was intended to be a phase Ib/II trial, but after completing Phase 1b and confirming the safe combination dose, the sponsor decided not to conduct Phase II.

Conditions

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Ovarian Cancer

Keywords

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Avelumab Carboplatin Primary Peritoneal Cancer Fallopian Tube Cancer Platinum sensitive ovarian cancer Deoxy ribonucleic acid (DNA)-damage response inhibition

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A: Carboplatin + M6620 + Avelumab

Group Type EXPERIMENTAL

M6620

Intervention Type DRUG

Participants received 90 milligrams per square meter (mg/m\^2) of M6620, intravenously (IV) on Day 2 of every 3 weeks (Q3W) cycle for a maximum of 6 cycles in combination treatment with carboplatin and avelumab on Day 1. The M6620 dose may be de-escalated to 60 mg/m\^2, or 40 mg/m\^2.

Avelumab

Intervention Type DRUG

Participants received IV infusion of avelumab 1600 mg on Day 1 of each Q3W cycle for maximum of 6 cycles in combination treatment with carboplatin and M6620. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.

Carboplatin

Intervention Type DRUG

Participants received carboplatin area under the concentration-time curve 5 on Day 1 of each Q3W cycle for a maximum of 6 cycles in combination treatment with avelumab and M6620.

Interventions

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M6620

Participants received 90 milligrams per square meter (mg/m\^2) of M6620, intravenously (IV) on Day 2 of every 3 weeks (Q3W) cycle for a maximum of 6 cycles in combination treatment with carboplatin and avelumab on Day 1. The M6620 dose may be de-escalated to 60 mg/m\^2, or 40 mg/m\^2.

Intervention Type DRUG

Avelumab

Participants received IV infusion of avelumab 1600 mg on Day 1 of each Q3W cycle for maximum of 6 cycles in combination treatment with carboplatin and M6620. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.

Intervention Type DRUG

Carboplatin

Participants received carboplatin area under the concentration-time curve 5 on Day 1 of each Q3W cycle for a maximum of 6 cycles in combination treatment with avelumab and M6620.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Female participants with recurrent epithelial ovarian cancer who have disease progression following maintenance treatment with a PARPi as defined below:

1. Participant must have histologically diagnosed epithelial ovarian, primary peritoneal, or fallopian tube cancer, with nonmucinous histology
2. Participants must have completed at least 2 previous courses of platinum containing therapy (for example, carboplatin or cisplatin) and had documented response (complete response \[CR\] or partial response \[PR\]) to the last platinum-based treatment prior to treatment with a PARPi
3. Participant has received the last dose of platinum-containing treatment at least 6 months prior to study enrollment
4. Participant has documented disease progression (radiological) after at least 4 months of maintenance treatment with PARPi following a response to platinum-based chemotherapy.
* Confirmed breast cancer gene (BRCA) 1/2 mutation status or agree to its testing on samples collected in the study.
* Available formalin-fixed, paraffin-embedded (FFPE) tumor biopsies.
* Part A: Optional 2 paired on-treatment biopsies on Day 2 of Cycle 1 (first biopsy) and Day 2 of Cycle 1 or Cycle 2 (second biopsy) respectively, before and after M6620 administration, if assessed as feasible at low risk by the interventional radiologist.
* Part B: Histological tissue specimen (tissue block or 8 to 10 unstained slides) must be available. An archival tumor biopsy is acceptable if obtained after the last progression on PARPi treatment and is less than 4 months old. Otherwise, participants must be willing to undergo mandatory biopsy during the Screening Period to obtain sufficient tissue for histological assessment. Participants need to have an attempted biopsy. However, participants who have measurable disease documented by a radiologist as not feasible or safe to be biopsied are eligible to enter the study
* Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

Exclusion Criteria

* Treatment with a nonpermitted drug/intervention as listed below:

1. Concurrent anticancer treatment (e.g., cytoreductive therapy, radiotherapy, immune therapy, cytokine therapy, monoclonal antibody, or targeted small molecule therapy) or any study intervention within 4 weeks prior to start of study intervention, or not recovered from AEs related to such therapies
2. History of prior dose reductions or dose interruptions while receiving cisplatin or carboplatin due to toxicity from the platinum or intolerance to either agent, unless discussed with and approved by the Sponsor Medical Monitor
3. Prior treatment with a PD-1/PD-L1 targeting agent
* Current use of the following medications at the time of enrollment:

1. Immunotherapy or immunosuppressive drugs at the time of enrollment (for example (e.g.,) chemotherapy or systemic corticosteroids) EXCEPT for (a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra articular injection), (b) systemic corticosteroids at physiologic doses less than or equals to (≤) 10 milligram per day (mg/day) of prednisone or equivalent, (c) steroids as premedication for hypersensitivity reactions (e.g., computed tomography \[CT\] scan premedication)
2. Growth factors EXCEPT where indicated for treatment of study intervention related myelosuppression and for prophylaxis of repeat myelosuppression after initial occurrence
3. Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or known to potentially interfere with major organ function (e.g., hypericin)
4. Other DNA damage repair inhibitors (except PARPi) (e.g., inhibitors of ATR, ataxia telangiectasia mutated \[ATM\] kinase, DNA-dependent protein kinase \[DNA-PK\], or Wee kinases).
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

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Marin Cancer Care, Inc.

Greenbrae, California, United States

Site Status

The Stamford Hospital

Stamford, Connecticut, United States

Site Status

Covenant Health Care

Saginaw, Michigan, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Mount Sinai - PRIME

New York, New York, United States

Site Status

Peggy & Charles Stephenson Oklahoma Cancer Ctr

Oklahoma City, Oklahoma, United States

Site Status

Mary Crowley Cancer Research Centers

Dallas, Texas, United States

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

CHU Sart Tilman

Liège, , Belgium

Site Status

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, , Belgium

Site Status

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom

Site Status

Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Site Status

Royal Marsden Hospital

London, , United Kingdom

Site Status

Countries

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Germany Italy United States Belgium United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2018-001534-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS201943_0029

Identifier Type: -

Identifier Source: org_study_id