Clinical Trials /

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

NCT03704467

Description:

The study is 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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase Ib/II Study of Carboplatin + M6620 + Avelumab in PARPi-resistant Ovarian Cancer
  • Official Title: A Phase Ib Safety Run-in and Randomized Phase II, Open-label Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of M6620 in Combination With Avelumab and Carboplatin in Comparison to Standard of Care Therapy in Participants With PARPi-resistant Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Clinical Trial IDs

  • ORG STUDY ID: MS201943_0029
  • SECONDARY ID: 2018-001534-17
  • NCT ID: NCT03704467

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
M6620Carboplatin + M6620 + Avelumab (Part A, Part B)
AvelumabCarboplatin + M6620 + Avelumab (Part A, Part B)
CarboplatinCarboplatin + M6620 + Avelumab (Part A, Part B)
PaclitaxelStandard of care (SoC) treatment (Part B)
GemcitabineStandard of care (SoC) treatment (Part B)
BevacizumabStandard of care (SoC) treatment (Part B)
Pegylated Liposomal Doxorubicin (PLD)Standard of care (SoC) treatment (Part B)

Purpose

The study is 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.

Trial Arms

NameTypeDescriptionInterventions
Carboplatin + M6620 + Avelumab (Part A, Part B)ExperimentalPart A: Participants will receive avelumab and carboplatin followed by M6620 as a safety run in cohort (non-randomized); Part B participants will be randomized to receive avelumab and carboplatin followed by M6620 (dose-expansion phase II).
  • M6620
  • Avelumab
  • Carboplatin
Standard of care (SoC) treatment (Part B)Active ComparatorPart B participants will be randomized to receive standard of care chemotherapy (Investigator choice of 2 options).
  • Carboplatin
  • Paclitaxel
  • Gemcitabine
  • Bevacizumab
  • Pegylated Liposomal Doxorubicin (PLD)

Eligibility Criteria

        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 RECIST v1.1.

          -  Other protocol defined inclusion criteria could apply

        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).

          -  Other protocol defined exclusion criteria could apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Occurrence of Dose-limiting Toxicities (DLTs) During the DLT Observation Period
Time Frame:Up to 3 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part A: Occurrence of Treatment-emergent Adverse Events (TEAEs) and Treatment-related Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Part A and B: Number of Participants With Confirmed Best Overall Response (BOR)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Part A and B: Progression-free survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Part A and B: Duration of response (DOR)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Part A and B: Time to progression (TTP)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Part A and B: Time to first subsequent therapy (TFST)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Part A and B: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of M6620 and Avelumab
Time Frame:Pre-dose, 0, 1, 2, 3 and 6 hours post-dose on Day 2 Cycle 1; post-dose 47 hours on Day 4 Cycle 1; pre-dose and at 0 hour on Day 2 Cycle 2 (each Cycle is 21 days)
Safety Issue:
Description:
Measure:Part A and B: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M6620 and Avelumab
Time Frame:Pre-dose, 0, 1, 2, 3 and 6 hours post-dose on Day 2 Cycle 1; post-dose 47 hours on Day 4 Cycle 1; pre-dose and at 0 hour on Day 2 Cycle 2 (each Cycle is 21 days)
Safety Issue:
Description:
Measure:Part A and B: Area Under the Concentration-time Curve (AUC) of M6620 and Avelumab Over the Dosing Interval From Time Zero to Tau hour
Time Frame:Pre-dose, 0, 1, 2, 3 and 6 hours post-dose on Day 2 Cycle 1; post-dose 47 hours on Day 4 Cycle 1; pre-dose and at 0 hour on Day 2 Cycle 2 (each Cycle is 21 days)
Safety Issue:
Description:
Measure:Part A and B: Terminal Rate Constant (λz) of M6620 and Avelumab
Time Frame:Pre-dose, 0, 1, 2, 3 and 6 hours post-dose on Day 2 Cycle 1; post-dose 47 hours on Day 4 Cycle 1; pre-dose and at 0 hour on Day 2 Cycle 2 (each Cycle is 21 days)
Safety Issue:
Description:
Measure:Part A and B : Maximum Observed Drug Concentration (Cmax) of M6620 and Avelumab
Time Frame:Pre-dose, 0, 1, 2, 3 and 6 hours post-dose on Day 2 Cycle 1; post-dose 47 hours on Day 4 Cycle 1; pre-dose and at 0 hour on Day 2 Cycle 2 (each Cycle is 21 days)
Safety Issue:
Description:
Measure:Part A: Minimum Observed Drug Concentration (Cmin) of M6620 and Avelumab
Time Frame:Pre-dose, 0, 1, 2, 3 and 6 hours post-dose on Day 2 Cycle 1; post-dose 47 hours on Day 4 Cycle 1; pre-dose and at 0 hour on Day 2 Cycle 2 (each Cycle is 21 days)
Safety Issue:
Description:
Measure:Part A and B: Time to Reach the Maximum Plasma Concentration (tmax) of M6620 and Avelumab
Time Frame:Pre-dose, 0, 1, 2, 3 and 6 hours post-dose on Day 2 Cycle 1; post-dose 47 hours on Day 4 Cycle 1; pre-dose and at 0 hour on Day 2 Cycle 2 (each Cycle is 21 days)
Safety Issue:
Description:
Measure:Part A and B: Apparent Terminal Half-life (t1/2) of M6620 and Avelumab
Time Frame:Pre-dose, 0, 1, 2, 3 and 6 hours post-dose on Day 2 Cycle 1; post-dose 47 hours on Day 4 Cycle 1; pre-dose and at 0 hour on Day 2 Cycle 2 (each Cycle is 21 days)
Safety Issue:
Description:
Measure:Part B: Occurrence of TEAEs and Treatment-related AEs and Immune-related Adverse Events (irAEs) According to NCI-CTCAE
Time Frame:Up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

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

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