Phase II study of pembrolizumab and bevacizumab in combination with platinum-based chemotherapy followed by pembrolizumab, bevacizumab and olaparib in patients with platinum-sensitive recurrent ovarian cancer

JRCT ID: jRCT2031210397

Registered date:29/10/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: ovarian cancer
• Date of first enrollment: 25/07/2022
• Target sample size: 35
• Study type: Interventional
• Intervention(s): Platinum-based chemotherapy, pembrolizumab and bevacizumab will be continued up to six 21-day cycles until discontinuation criteria are met. Patients with stable disease (SD) or better and have received six cycles of platinum-based chemotherapy will receive olaparib, pembrolizumab, and bevacizumab for up to two years or 35 cycles in a 21-day cycle.

Outcome(s)

• Primary Outcome: Two-year progression-free survival rate

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

1. Participant is at least 20 years of age on the day of signing informed consent with histologically confirmed epithelial ovarian cancer (excluding borderline ovarian tumor) excluding mucinous carcinoma.
2. Participant has received one or two regimen of PBC (3 cycles or more) as prior therapy with clinical CR or PR after the last PBC.
3. Participant has documentation of progressive disease at least 6 months from completion of last PBC (platinum-sensitive).
4. Participant with measurable disease based on RECIST 1.1 at screening
5. Participant is able to provide a core or excisional biopsy of a tumor for testing of PD-L1 status, etc.
6. Participant with Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 at the screening
7. Participant has a life expectancy of at least 12 weeks as determined by the investigators.
8. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one 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 210 days after the last dose of study treatment.
9. Participant has provided written informed consent for the study (legally acceptable representative is acceptable if applicable).
10. Participant has adequate organ function.

Exclude criteria

1. A WOCBP who has a positive urine pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
3. Participant has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the first dose of study drug.
4. Participant has received prior radiotherapy within 2 weeks of the first dose of study drug.
5. Participant has received major surgery within 4 weeks prior to the first dose of study drug.
6. Participant has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
7. Participant is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug.
8. Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
9. Participant has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
10. Participant has known active CNS metastases and/or carcinomatous meningitis.
11. Participant has severe hypersensitivity ( >=Grade 3) to the study treatment and/or any of its excipients.
12. Participant has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
13. Participant has a history of (non-infectious) pneumonitis/interstitial lung disease that required treatment with steroids or has current pneumonitis/interstitial lung disease.
14. Participant has an active infection requiring systemic therapy.
15. Participant has a known history of Human Immunodeficiency Virus (HIV) infection.
16. 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.
17. Participant has received colony-stimulating factors (granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the first dose of study drug.
18. Participant has clinically serious cardiovascular/cerebrovascular diseases (eg, cerebrovascular accident/stroke [less than 6 month prior to enrollment], myocardial infarction [less than 6 month prior to enrollment], uncontrolled and potentially reversible cardiac conditions [unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 msec, electrolyte disturbances, hypertension defined as systolic >150 mmHg or diastolic >90 mmHg etc.] or participant has congenital long QT syndrome).
19. Participant has known abdominal fistula, gastrointestinal fistula or gastrointestinal perforation and/or higher risks of bleeding.
20. Participant has either myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML.
21. Participant is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued prior to the first dose of study drug.
22. Participant is currently receiving either strong (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued prior to the first dose of study drug.
23. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption).
24. Participant has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
25. Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 210 days after the last dose of study treatment.
26. Participant has had an allogenic tissue/solid organ transplant.
27. 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 participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the investigators.

Related Information

• Primary Sponsor: Hasegawa Kosei
• Source(s) of Monetary Support: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., N.J., U.S.A.,MSD K.K.