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

NCT03704467 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: MS201943_00292018-001534-17
• Study Type: interventional
• Target: 3
• Locations: 3 countries
• Sites: 13

Brief Summary

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.

Conditions

Ovarian Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Part A: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT: any death not clearly due to underlying disease/extraneous causes/Grade(Gr) \>=3 nonhematologic/Gr\>=4 hematologic toxicity that was probably/definitely related to any of study interventions, individually/combination that occurred during DLT observation period, except for any of following: Gr3 infusion-related reaction; Transient (\<=6hr) Gr3 flu-like symptoms/fever, controlled with medical management; Transient (\<=72hr) Gr3 fatigue, local reactions, headache, nausea/emesis; Gr3 diarrhea, skin toxicity, liver function test increase; Single laboratory values out of normal range and controlled with medical management; Tumor flare phenomenon: local pain, irritation/rash, localized at sites of known/suspected tumor; Neutropenia (Gr3/4) for \<7 days not associated with any infection; Gr3 thrombocytopenia for \<7 days without clinically significant bleeding and not requiring platelet transfusion; Symptomatic thyroid dysfunction manageable with treatment.

  Up to 3 weeks

Secondary Outcomes (14)

• Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs

  Time from first dose of study treatment up to 230 days

• Part A: Number of Participants With Confirmed Best Overall Response (BOR)

  Time from first dose of study treatment up to 230 days

• Part A: Progression-Free Survival (PFS)

  Time from first dose of study treatment up to 230 days

• Part A: Duration of Response (DoR)

  Time from first dose of study treatment up to 230 days

• Part A: Time to Progression (TTP)

  Time from first dose of study treatment up to 230 days

Study Arms (1)

Part A: Carboplatin + M6620 + Avelumab

EXPERIMENTAL

Drug: M6620; Drug: Avelumab; Drug: Carboplatin

Interventions

M6620 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.

Part A: Carboplatin + M6620 + Avelumab

Avelumab 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.

Part A: Carboplatin + M6620 + Avelumab

Carboplatin 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.

Part A: Carboplatin + M6620 + Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants with recurrent epithelial ovarian cancer who have disease progression following maintenance treatment with a PARPi as defined below:
• Participant must have histologically diagnosed epithelial ovarian, primary peritoneal, or fallopian tube cancer, with nonmucinous histology
• 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
• Participant has received the last dose of platinum-containing treatment at least 6 months prior to study enrollment
• 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).

You may not qualify if:

• Treatment with a nonpermitted drug/intervention as listed below:
• 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
• 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
• Prior treatment with a PD-1/PD-L1 targeting agent
• Current use of the following medications at the time of enrollment:
• 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)
• Growth factors EXCEPT where indicated for treatment of study intervention related myelosuppression and for prophylaxis of repeat myelosuppression after initial occurrence
• Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or known to potentially interfere with major organ function (e.g., hypericin)
• 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).

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (13)

Marin Cancer Care, Inc.

Greenbrae, California, 94904, United States

Location

The Stamford Hospital

Stamford, Connecticut, 06904, United States

Location

Covenant Health Care

Saginaw, Michigan, 48604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065-6007, United States

Location

Mount Sinai - PRIME

New York, New York, 11041, United States

Location

Peggy & Charles Stephenson Oklahoma Cancer Ctr

Oklahoma City, Oklahoma, 73104, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75251, United States

Location

UZ Leuven

Leuven, Belgium

Location

CHU Sart Tilman

Liège, Belgium

Location

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, Belgium

Location

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom

Location

Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Location

Royal Marsden Hospital

London, United Kingdom

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

avelumab; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Limitations and Caveats

The study was early discontinued and Part 2 (randomized controlled) was not conducted as per Sponsor's decision.

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2018
• First Posted: October 12, 2018
• Study Start: March 4, 2019
• Primary Completion: November 6, 2019
• Study Completion: November 6, 2019
• Last Updated: November 13, 2020
• Results First Posted: November 13, 2020

Record last verified: 2020-10

Locations

US (7); GB (3); BE (3)