Pembrolizumab and Bevacizumab With Chemotherapy Followed by Pembrolizumab, Bevacizumab and Olaparib in Recurrent Ovarian Cancer

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

This trial is a multicenter, single-arm, phase II study evaluating the efficacy of pembrolizumab and bevacizumab in combination with platinum-based chemotherapy (PBC) followed by pembrolizumab, bevacizumab and olaparib as a maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer.This study is planned to enroll eligible 35 patients from multiple study sites in Japan.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Ovarian Epithelial
• Intervention / Treatment: Biological: pembrolizumab; Drug: olaparib; Biological: bevacizumab; Drug: carboplatin; Drug: paclitaxel; Drug: docetaxel

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kosei Hasegawa, MD, PhD; Phone Number: 5627 +81-42-984-4111; Email: koseih@saitama-med.ac.jp
• Study Contact Backup: Name: Miwa Hirai; Phone Number: +81-3-6779-8222; Email: saint-ov02@cmic.co.jp

Study Locations

• Japan
  • Saitama
    • Hidaka, Saitama, Japan, 3501298
      • Recruiting
      • Saitama Medical Uiversity International Medical Center
      • Contact: Kosei Hasegawa, MD; Phone Number: +81-42-984-4641; Email: koseih@saitama-med.ac.jp
      • Principal Investigator: Kosei Hasegawa, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion 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 only one regimen of PBC (3 cycles or more) as prior therapy with clinical CR (determined by negative clinical examination and a normal CA-125 level).
3. Participant has documentation of progressive disease at least 6 months from completion of 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. Participant has adequate organ function.

Exclusion Criteria:

1. A Women of Childbearing Potential (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib; Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.

Biological: pembrolizumab; pembrolizumab 200 mg every three weeks (Q3W); Other Names: KEYTRUDA; Drug: olaparib; olaparib 300 mg twice daily (BID) during maintenance period; Other Names: LYNPARZA; Biological: bevacizumab; bevacizumab 15 mg/kg Q3W; Other Names: AVASTIN; Drug: carboplatin; carboplatin AUC=5 or 6 Q3W during treatment period; Drug: paclitaxel; paclitaxel 175 mg/m2 Q3W during treatment period; Drug: docetaxel; docetaxel 60 ~ 70 mg/m2 Q3W during treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Two-year progression-free survival rate	Two-year progression-free survival rate after administration of pembrolizumab and bevacizumab in combination with PBC followed by pembrolizumab, bevacizumab and olaparib as a maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer based on RECIST 1.1.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS after administration of the study treatment based on RECIST 1.1	3 years
PFS in maintenance period by chemotherapy responder	PFS in maintenance period in patients who assessed CR or PR at last tumor assessment before entering maintenance period based on RECIST 1.1	3 years
Objective Response Rate (ORR)	ORR after administration of the study treatment based on RECIST 1.1	3 years
Disease Control Rate (DCR)	DCR after administration of the study treatment based on RECIST 1.1	3 years
Duration of Response (DOR)	DOR after administration of the study treatment based on RECIST 1.1	3 years
One-year progression-free survival rate	One-year progression-free survival rate after administration of the study treatment based on RECIST 1.1.	1 year
Overall Survival (OS)	OS after administration of the study treatment using Kaplan-Meier method	3 years
Incidence of adverse events	The number and proportion of participants with adverse events as assessed by CTCAE v5.0	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Exploratory assessment of relationship between biomarkers and efficacy endpoints if possible	3 years

Collaborators and Investigators

• Sponsor: Kosei Hasegawa, MD, PhD
• Investigators: Principal Investigator: Kosei Hasegawa, MD, PhD, Saitama Medical University International Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2022
• Primary Completion (Anticipated): November 30, 2024
• Study Completion (Anticipated): November 30, 2024

Study Registration Dates

• First Submitted: November 26, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: ovarian cancer, pembrolizumab, olaparib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Docetaxel; Carboplatin; Paclitaxel; Olaparib; Bevacizumab; Pembrolizumab
• Other Study ID Numbers: SaINT-ov02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes