Niraparib Rechallenge After Surgery in Ovarian Cancer Patients With Oligometastatic Progression

Inclusion Criteria:

1. Written informed consent form (ICF) prior to beginning specific protocol procedures.

2. Female patients ≥ 18 years of age.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

4. Patients must have a life expectancy ≥16 weeks.

5. Histologically confirmed high grade serous or endometrioid OC who have an OMP duringor after the first maintenance therapy with any PARPi.

6. Oligometastatic progression defined as 1-5 lesions (according to European Societyfor Radiotherapy and Oncology [ESTRO] and American Society for Radiation Oncology [ASTRO] consensus).

7. Patients must have undergone secondary cytoreductive surgery with centrallyconfirmed no evidence of macroscopic residual tumor after surgery (completeresection).

8. Patients must have either normal or up to 2 x ULN CA 125 level.

9. Documented breast cancer gene 1/2 (BRCA1/2) status and homologous recombination (HR)status.

10. Patients who have received prior iPARP monotherapy or iPARP together withbevacizumab as maintenance treatment.

11. Patients should have had benefit of prior PARPi defined by exposure for ≥12 months (at least ≥ 18 months for patients who have a BRCA1/2 mutation) from initiation ofPARPi maintenance until the date of OMP or have experienced a tumor progressionafter treatment completion. Tumor progression must have been confirmed by computedtomography (CT) and/or PET-CT scan.

12. If prior treatment was niraparib, no significant toxicity or need for treatmentdiscontinuation was required.

13. Willingness to provide formalin fixed, paraffin embedded (FFPE) tumor tissue fromprimary, if available, and secondary surgeries and blood samples at screening, every 3 cycles (12 weeks), and at the end of treatment (EoT).

14. Able to take oral medications.

15. Patients must start treatment 3 to 6 weeks from surgery, once recovered fromsurgery.

16. Women of childbearing potential who engage in heterosexual intercourse must agree touse institution specified method(s) of contraception and must refrain from donatingeggs in the time period specified in the study protocol. Women of childbearingpotential must have a negative serum or a highly sensitive urine pregnancy testwithin 72 hours before study treatment initiation.

17. Patient has adequate bone marrow, liver, and renal function:

• Hematological: White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophilcount (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 9.0g/dL (≥ 5.6 mmol/L).

• Hepatic: total bilirubin ≤ institutional upper limit of normal (ULN) (exceptfor Gilbert's syndrome); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartatetransaminase (AST) and alanine transaminase (ALT) ≤ 1.5 times ULN. 11).

• Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2for patients with creatinine levels above institutional normal.

18. Patients must be accessible for treatment follow-up.

Exclusion Criteria:

1. Patients with symptomatic or systemic progressive disease not fulfilling OMP diseasecriteria.

2. Patients with residual disease after secondary cytoreductive surgery.

3. Patients with persistent toxicities (> Common Terminology Criteria for AdverseEvents (CTCAE) grade 2) caused by previous cancer therapy.

4. Patients with central nervous system (CNS) metastases at baseline (post-secondarycytoreductive surgery).

5. Patients unable to swallow oral medication or with any life-threatening illness,medical condition, or organ system dysfunction which, in the investigator's opinion,could compromise the subject's safety, interfere with the absorption or metabolismof niraparib, or put the study outcomes at undue risk.

6. Patients with clinically significant cardiovascular disease such as uncontrolledhypertension, uncontrolled or symptomatic arrythmias, congestive heart failure (CHF), or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York HeartAssociation (NYHA) Functional Classification.

7. Patients treated with previous PARPi therapy who have any known, persistent (>4weeks), ≥Grade 3 anemia, neutrophil count decrease or platelet count decrease.

8. Patients with known history of human immunodeficiency virus (HIV), or activehepatitis C Virus (HCV), or active hepatitis B Virus (HBV) infection, or anyuncontrolled active systemic infection requiring intravenous antibiotics.

9. Patients with known hypersensitivity or allergy to prior niraparib treatment or anyof the excipients of the product.

10. Patients who have received a transfusion of platelets or red blood cells,colony-stimulating factors or have any other laboratory abnormality within 2 weeksprior niraparib treatment that might confound or interfere with the study result.

11. Patients must not be simultaneously enrolled in any clinical trial of niraparib orany other investigational therapy.

12. Patients who are pregnant or breastfeeding or expecting to conceive children withinthe projected duration of the study treatment.

13. Patients with myelodysplastic syndrome (MSD)/Acute myeloid leukemia (AML), withhistory of MSD/AML or with features suggestive of MDS/AML.

14. Previous allogenic bone marrow transplant or double umbilical cord bloodtransplantation (dUCBT).

15. Other malignancy unless curatively treated with no evidence of disease ≥ 5 yearsprior to study enrollment. Note: Patients with adequately non-melanoma skin cancer,curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) andstage 1 low grade endometrial carcinoma are not excluded.

16. Vaccination with any live virus vaccine within 28 days prior study treatmentinitiation.