PRECISE: This phase II trial is evaluating the effectiveness of using a targeted therapy (Pamiparib) to treat patients with high grade serous ovarian cancer or carcinosarcomaPamiparib in fusion positive, reversion negative high grade serous cancer or carcinosarcoma with BRCA1/2 gene mutations if progression on substrate poly ADP ribose polymerase inhibitor (PARPI) or Chemotherapy

Exclusion

- Pre-Screening

1. Patients with a clear cell, mucinous, or other non-high grade serous histological subtype

2. Prior treatment with non-substrate P-gp PARPi (pamiparib or veliparib)

   • Prior treatment with substrate PARPi is allowed (olaparib, niraparib, rucaparib, and talazoparib)
3. Patients who are pregnant or nursing
4. Patient has a diagnosis of myelodysplastic syndrome (MDS)

5. Patient has other diagnoses of malignancy

   • Except for surgically excised non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, adequately treated non-invasive bladder cancer, ductal carcinoma in situ treated surgically with curative intent, or a malignancy diagnosed >2 years ago with no current evidence of disease and no therapy ≤2 years prior to pre-screening
6. Prior radiation therapy to target lesions in the absence of documented progression at the treated target lesion
7. Patient has uncontrolled pleural effusion, pericardial effusion, or ascites requiring weekly recurrent drainage procedures
8. Known history of intolerance to the excipients of the pamiparib capsule
9. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena ≤6 months prior to registration to pre-screening

10. Previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal disease, or any other disease-causing malabsorption syndrome

    • Gastroesophageal reflux disease under treatment with proton-pump inhibitors is allowed

Exclusion Criteria - Main Study

1. Patients who have received chemotherapy, biologic therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or herbal remedies ≤ 5 half-lives if the half-life is known, ≤ 14 days if not known, prior to registration to the main study

   • Bisphosphonate and denosumab use are allowed on study, if administered at a stable dose > 28 days prior to registration to the main study
2. The use or anticipated need for food or drugs known to be strong CYP3A inducers (Appendix 7) ≤ 5 half-lives if the half-life is known or ≤ 14 days if not known prior to registration to the main study

3. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 14 days prior to registration to the main study, or anticipation of need for major surgical procedure during the course of the study

   • Placement of vascular access device is not considered major surgery
4. Prior radiation therapy ≤ 14 days prior to registration to the main study to non-target lesions. Patients who have received palliative radiotherapy of non-target lesions for local symptom control > 14 days prior to registration to the main study must have stabilisation of any AEs or a return to baseline prior to registration to the main study
5. Leptomeningeal disease or uncontrolled, untreated brain metastases

6. Patients with a history of treated and asymptomatic brain metastases are eligible, provided they meet all of the following:

   • Only supratentorial metastases
   • Brain imaging at screening without evidence of interim progression
   • No ongoing requirement for corticosteroids as therapy for brain metastases
   • Anticonvulsants at a stable dose allowed (except for contraindicated medications carbamazepine and phenytoin)
   • No stereotactic radiation or whole-brain radiation ≤ 14 days prior to registration to the main study

7. Any of the following cardiovascular criteria:

   • Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days prior to registration to the main study
   • Symptomatic pulmonary embolism ≤ 28 days prior to registration to the main study
   • Any history of acute myocardial infarction ≤ 6 months prior to registration to the main study
   • Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV (refer to Appendix 8) ≤ 6 months prior to registration to the main study
   • Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months prior to registration to the main study
   • Any history of cerebrovascular accident (CVA) ≤ 6 months prior to registration to the main study

8. Active infection requiring systemic treatment, acute/viral hepatitis or active chronic hepatitis B or C or active tuberculosis

   • Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is > 500 IU/mL or patients with active hepatitis C should be excluded. Note: Inactive hepatitis B surface antigen carriers, treated and stable hepatitis B (HBV DNA < 500 IU/mL), and cured hepatitis C patients can be enrolled