Advanced epithelial ovarian 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)
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant has histologically confirmed FIGO Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with highgrade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer 2. Participant has just completed primary debulking surgery or is eligible for primary or interval debulking surgery. Participant must be randomized within 56 days of primary debulking surgery 3. Participant is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the adjuvant or neoadjuvant setting 4. Participant that is a candidate for neoadjuvant chemotherapy has a CA-125 (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than 25 5. Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA1/2 and PD-L1 status prior to randomization 6. Participant is female and at least 18 years of age on the day of signing informed consent 7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to initiating chemotherapy in the lead-in period and within 7 days prior to randomization 8. A female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least 1 of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and olaparib (or olaparib placebo) and at least 210 days following the last dose of chemotherapy or bevacizumab (if administered) 9. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for future biomedical research; however, the participant may participate in the main study without participating in future biomedical research 10. Participant has adequate organ function; all screening laboratory tests should be performed within 7 days of initiating chemotherapy in the lead-in period. Hematological parameters must be reassessed and adequate after the lead-in period and within 7 days prior to randomization Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 800 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 286
Exclusion criteria
Exclusion criteria: 1. Participant has mucinous, germ cell, or borderline tumor of the ovary 2. Participant has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2 3. Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis 4. Participant either has myelodysplastic syndrome (MSD)/acute myeloid leukemia (AML)or has features suggestive of MDS/AML 5. Participant has a known additional malignancy that is progressing or has required active treatment in the last 3 years 6. Participant has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy administered during the lead-in period 7. Participant has known active central nervous system metastases and/or carcinomatous meningitis. 8. Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization 9. Participant has an active autoimmune disease that has required systemic treatment in the past 2 years 10. Participant has a known history of active tuberculosis (TB; Bacillus Tuberculosis) 11. Participant has an active infection requiring systemic therapy 12. Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator 13. Participant has received colony-stimulating factors within 2 weeks prior to randomization 14. Participant is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection 15. Participant has had surgery to treat borderline tumors, early stage EOC, or fallopian tube cancer <6 months prior to screening 16. Participant has a known psychiatric or substance abuse disorder that would interfere with the ability to cooperate with the requirements of the study 17. Participant has a known history of human immunodeficiency virus (HIV) infection. 18. Participant has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 19. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption 20. Participant has current, clinically relevant bowel obstruction (including sub-occlusive disease), abdominal fistula or gastrointestinal perforation, related to underlying EOC 21. Participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to randomization 22. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of chemotherapy in the lead-in period and within 72 hours prior to randomization, is pregnant or breastfeeding, or is expecting to conceive children within the projected duration of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare the progressionfree survival (PFS) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) 2. To compare overall survival (OS) ; Secondary Objective: 1.Compare the PFS as assessed by blinded independent central review according to RECIST 1.1 2.Compare the PFS after next-line treatment (PFS2) following discontinuation of study treatment administration as determined by the investigator according to the local standard of clinical practice 3.Evaluate the safety and tolerability of pembrolizumab administered with chemotherapy and olaparib maintenance 4.Compare the GHS/QoL score using the EORTC, QLQC30 and abdominal/GI symptoms using the EORTC QLQOV28 abdominal/GI symptom scale 5.Compare the time to first subsequent anti-cancer treatment , the time to second subsequent anti-cancer treatment, and the time to discontinuation of study treatment or death ; Primary end point(s): 1) Progression-free survival (PFS) based on RECIST 1.1 as assessed by investigator 2) Overall survival (OS) ; Timepoint(s) of evaluation of this end point: 1) PFS and OS analysis around 30 months after the first participant is randomized, when at least 362 PFS events are observed for both comparisons 2) PFS and OS analysis around 36 months after the first participant is randomized, when at least 452 PFS events are observed for both comparisons 3) OS analysis around 52 months after the first participant is randomized, when at least 289 OS events are observed for both comparisons 4) Final Analysis: OS analysis around 66 months after the first participant is randomized, when at least 361 OS events are observed for both comparisons | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) PFS based on RECIST 1.1 as assessed by BICR 2) PFS after next-line treatment (PFS2) 3) Safety and tolerability of the 3 treatment groups ;Timepoint(s) of evaluation of this end point: 66 months after first particpanct is randomized | — |
Countries
Australia, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Russian Federation, South Africa, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed