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Olaparib Monotherapy and Olaparib + Pembrolizumab Combination Therapy for Ovarian Cancer (OLAPem)

Olaparib Monotherapy and Olaparib + Pembrolizumab Combination Therapy for Ovarian Cancer (OLAPem)

30

Thirty patients were given informed consent and participated in this study between November 2020 and December 2022. As planned, the number of participants was 10 in Cohort 1 and 20 in Cohort 2. The participant backgrounds for Cohort 1 and Cohort 2 were age 67.5 (52-78) and 62 (45-85), PS0 in 8 and 13, FIGO stage IIIC: 3 and 11, IVA: 2 and 0, IVB: 5 and 9, PD-L1 positive: 4 and 14, and BRCA1/2 mutation: 5 and 13, and all participants were high-grade serous carcinoma.

Two cycles of protocol treatment were completed in 9 in cohort 1 and 20 in cohort 2. There was one dose reduction of olaparib in cohort 1, four dose interruptions in cohort 1, and seven in cohort 2. There was no interruption of pembrolizumab.

Adverse events of any grade occurred in 100% of participants (n=10) in cohort 1 and 95% (n=19) in cohort 2. Grade 3 or higher adverse events occurred in 40% of participants (n=4) in cohort 1 and 35% (n=7) in cohort 2. The most common adverse events in Cohort 1 were nausea (70%), diarrhea (40%), and fatigue (20%). In Cohort 2, the most common adverse events were nausea (50%), anemia (45%), vomiting (30%), and diarrhea (20%). No immune-associated adverse events were observed in cohort 2.

The overall response rate (ORR) in cohort 1 was 50% (95% CI, 18.7 - 81.3), with no complete and five cases of partial response. Only one patient had a progressive disease. In cohort 2, the ORR was 70% (95% CI, 45.7 - 88.1), with no cases of complete response and 14 cases of partial response; no cases of progressive disease were observed.

The median follow-up period was 23.5 months (range: 20.7 - 28.0 months) in cohort 1 and 11.2 months (range: 5.4 - 19.4 months) in cohort 2. The 12-month progression-free survival (PFS) rate was 90% (95% CI: 47.3 - 98.5%) in cohort 1 and 91.7% (95% CI: 53.9 - 98.8%) in cohort 2. There were no deaths in either cohort during the observation period. Pathological response in patients with serous carcinoma and metastasis to the omentum who underwent surgery was evaluated using the chemotherapy response score (CRS). Seven patients from Cohort 1 and 13 from Cohort 2 were assessed. In cohort 1, the pathologic response rate was 100%, with one patient (14%) achieving a complete response (CRS 3). In cohort 2, the pathological response rate was 84.6%, with five patients (38%) achieving a complete response.

Preoperative olaparib therapy resulted in a high response rate in patients with advanced ovarian cancer with HRD. Furthermore, combination therapy with olaparib and pembrolizumab enhanced antitumor effects, and the presence of BRCA1/2 mutations was correlated with a positive response to both olaparib monotherapy and olaparib and pembrolizumab combination therapy.

July. 30, 2026

July. 30, 2026

https://doi.org/10.1158/1078-0432.CCR-25-4887

No

Mukohara Toru

National Cancer Center Hospital East

6-5-1 Kashiwanoha, Kashiwa-shi Chiba, Japan

OLAPem_core@east.ncc.go.jp

clinical trial coordinating committee

National Cancer Center Hospital East

6-5-1 Kashiwanoha, Kashiwa-shi Chiba, Japan

+81-4-7133-1111

OLAPem_core@east.ncc.go.jp

completed

Feb. 25, 2021

Interventional

single arm study, open(masking not used)

treatment purpose

2

1.Has given signed informed consent to participate in the clinical trial of her own will.
2. Is aged 20 years or older on the day of signing the informed consent.
3. Has been diagnosed with histologically confirmed, Stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer by the International Federation of Gynecology and Obstetrics (FIGO) staging system (2014), with a histological type of high-grade serous or Grade 3 endometrioid carcinoma.
4. Have measurable disease based on RECIST 1.1.
5. Is a candidate for debulking surgery.
6. Has an HRD-positive tumor.
7. Has an ECOG Performance Status of 0 or 1.
8. Laboratory test results within 21 days prior to enrollment have met the following organ function criteria. However, measurements within 14 days of blood transfusion or administration of granulocyte-colony stimulating factor (G-CSF) are excluded.
Neutrophil count >= 1,500/mm3
Platelet count >= 100,000/mm3
Hemoglobin >= 9.0 g/dL
Serum creatinine =< 1.5 x ULN, or creatinine clearance >= 50 mL/min
T-Bil =< 2.0 mg/dL
ALT and AST =< 100 U/L (=< 200 U/L if liver metastasis is present)
9. A woman of childbearing potential must agree to use contraception after signing the informed consent, throughout the study period, and until at least 120 days following the last dose of the study drug

1. Has received previous allogeneic bone-marrow transplantation.
2. Has concurrent interstitial lung disease/pneumonitis, or a history of (noninfectious) interstitial lung disease/pneumonitis that required treatment with steroids. Interstitial lung disease/pneumonitis includes radiation pneumonitis.
3. Has received prior antitumor therapy (e.g., chemotherapy, molecular-targeted therapy, therapeutic antibody, endocrine therapy, immunotherapy, and investigational therapy).
4. Has received surgery under general anesthesia within 28 days prior to enrollment. However, surgery to diagnose ovarian/fallopian tube/peritoneal cancer performed under general anesthesia is allowed.
5. Has received radiation or radioactive isotope therapy within 28 days prior to enrollment.
6. Has uncontrolled pericardial effusion, pleural effusion, or peritoneal effusion.
7. Has a history of cerebral infarction, cerebral hemorrhage, or transient cerebral ischemia within 180 days prior to enrollment.
8. Has a history of deep vein thrombosis or pulmonary embolism.
9. Is receiving systemic glucocorticoid therapy or systemic immunosuppressive therapy.
10. Has a history of autoimmune disease.
11. Is infected with human immunodeficiency virus (HIV).
12. Is infected with active* hepatitis B or hepatitis C.
*: Active hepatitis B is defined as HBs antigen positive.
13. Has a symptomatic infection within 14 days prior to enrollment.
14. Has received a live vaccine within 28 days prior to enrollment.
15. Has clinically critical cardiac disease (has a history of myocardial infarction or angina pectoris within 180 days prior to enrollment or has New York Heart Association [NYHA] class II or higher cardiac failure, uncontrolled arrhythmia, or QTc prolongation defined as QTc > 470 msec).
16. Has active brain metastasis or a tumor causing spinal cord compression.
17. Is pregnant or breastfeeding.
18. Has a history of severe allergy, anaphylaxis, or hypersensitivity induced by humanized chimeric antibodies.
19. Is allergic to biologics produced from Chinese hamster ovary (CHO) cells, carboplatin, or paclitaxel.
20. Has a known or suspected active malignancy that is different from the disease of interest in the clinical trial or has a history of other malignancy within 3 years prior to enrollment. However, cutaneous basal cell carcinoma and cervical carcinoma in situ are not part of this exclusion criterion.
21. Is unwilling to or unable to comply with the protocol.
22. Is not eligible to enroll in the clinical trial based on the judgment by the Investigator or Sub-investigator.

Female

Ovarian Cancer

Cohort 1 : Olaparib will be administered for 6 weeks before surgery.
Cohort 2 : Olaparib and Pembrolizumab will be administered simultaneously for 2 cycles(6 weeks) before surgery.

Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1.

The incidence of adverse events
Chemotherapy response score (CRS)
Progression-free survival (PFS)
Overall survival (OS)

+81-4-7133-1111

May. 20, 2020