PARPi-resistant Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10038977 Term: Retroperitoneal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification cod
Conditions
Interventions
Trade Name: Bavencio
Product Name: Bavencio
Product Code: MSB0010718C
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
Current Sponsor code: Avelumab
Concentrat
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female participants with recurrent epithelial ovarian cancer who have disease progression following maintenance treatment with a PARPi as defined below: 1.1 Participant must have histologically diagnosed epithelial ovarian, primary peritoneal, or fallopian tube cancer, with nonmucinous histology 1.2 Participants must have completed at least 2 previous courses of platinum containing therapy (eg, 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 1.3 Participant has received the last dose of platinum-containing treatment at least 6 months prior to study enrollment 1.4 Participant has documented disease progression (radiological) after at least 6 months of maintenance treatment with PARPi following a response to platinum-based chemotherapy. 2. Confirmed BRCA 1/2 mutation status or agree to its testing on samples collected in the study. 3. Available formalin-fixed, paraffin-embedded (FFPE) tumor biopsies. 3.1 Part A: Participant should be willing to undergo 2 paired on-treatment biopsies on Day 2 of Cycle 1 or Cycle 2, before and after M6620 administration, if assessed as feasible at low risk by the interventional radiologist. 3.2 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 6 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. 4. Measurable disease according to RECIST v1.1. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Treatment with a nonpermitted drug/intervention as listed below: 1.1. 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 1.2. 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 1.3. Prior treatment with a PD-1/PD-L1 targeting agent 2. Current use of the following medications at the time of enrollment: 2.1. Immunotherapy or immunosuppressive drugs at the time of enrollment (e.g., chemotherapy or systemic corticosteroids) EXCEPT for (a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra articular injection), (2) systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent, (3) steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) 2.2. Growth factors EXCEPT where indicated for treatment of study intervention related myelosuppression and for prophylaxis of repeat myelosuppression after initial occurrence 2.3. Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or known to potentially interfere with major organ function (e.g., hypericin) 2.4. 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To evaluate a safe, tolerable RP2D of M6620 when given in combination with avelumab + carboplatin in participants with PARPi-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer. Part B: To evaluate antitumor activity of avelumab + M6620 + carboplatin compared with the standard of care treatment in participants with PARPi-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer.;Secondary Objective: Part A: To evaluate the safety and tolerability of M6620 in combination with avel+carbo at the RP2D in participants with PARPi-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer. To evaluate the antitumor activity of M6620 in combination with avel+carbo at the RP2D in participants with PARPi-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer. To characterize the pharmacokinetic (PK) profiles of avel and M6620 when given in combination with carbo. To characterize the immunogenicity of avel in combination with M6620+carbo. Part B: To evaluate the safety and tolerability of M6620 in combination with avel+carbo. To further evaluate antitumor activity of avel+M6620+carbo compared with the standard of care treatment. To characterize the PK of avel and M6620 when given in combination with carboplatin. To characterize the immunogenicity of avel in combination with M6620+carbo.;Primary end point(s): Part A: Occurrence of dose-limiting toxicities (DLTs) during the DLT observation period. Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1;Timepoint(s) of evaluation of this end point: Part A: Up to 3 weeks. Part B: Up to 3 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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). -Confirmed (ir) best overall response (BOR). -Progression-free survival (PFS) from date of first dose of study intervention until progressive disease (PD) or death. -(ir) Duration of response (DOR) as assessed from (ir) complete response (CR) or (ir) partial response (PR) until (ir) PD, death, or last tumor assessment. -(ir) Time to progression (TTP) from first dose of study intervention until PD. -All the above by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), and/or cancer antigen 125 (CA-125) response (Gynecologic Cancer InterGroup [GCIG] criteria), as assessed by the Investigator. -Time to first subsequent therapy (TFST) -PK parameter estimates for M6620 and summary statistics for avelumab. -Immunogenicity of avelumab in combination therapy, as measured by antidrug antibody (ADA) assay. Part B: -Occurrence of TEAEs and treatment-related AEs according to NCICTCAE. -PFS according to irRECIST; GCIG CA-125 as assessed by the Investigator. -Confirmed (ir) BOR according to RECIST 1.1, irRECIST, and GCIG CA-125. - (ir) DOR assessed from (ir) CR or (ir) PR until (ir) PD, death, or last tumor assessment. - (ir) TTP - TFST - PK parameter estimates for M6620 and summary statistics for avelumab - Immunogenicity of avelumab in combination therapy as measured by ADA assay.;Timepoint(s) of evaluation of this end point: Up to 3 years | — |
Countries
Belgium, Italy, United Kingdom, United States
Contacts
Public ContactCommunication Centre Merck KGaA
Merck KGaA
Outcome results
None listed