Overview

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

Status:
Completed
Trial end date:
2019-11-06
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
EMD Serono Research & Development Institute, Inc.
Collaborators:
Merck KGaA
Merck KGaA, Darmstadt, Germany
Treatments:
Albumin-Bound Paclitaxel
Antibodies, Monoclonal
Avelumab
Bevacizumab
Carboplatin
Gemcitabine
Paclitaxel
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