Phase Ib/II Study of Carboplatin + M6620 + Avelumab in PARPi-resistant Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: M6620; Avelumab; Carboplatin
Intervention description: 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.; 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.; 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 MeSH terms: Carboplatin; Avelumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Avelumab; Carboplatin; Primary Peritoneal Cancer; Fallopian Tube Cancer; Platinum sensitive ovarian cancer; Deoxy ribonucleic acid (DNA)-damage response inhibition

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.
    

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 Response Evaluation Criteria in Solid Tumors version
             1.1 (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