PRECISE: This is a phase II trial evaluating the effectiveness of targeted therapy (Pamiparib) for the treatment of patients with recurrent High Grade Serous Ovarian Cancer or carinosarcomaA Phase II, Signal-Seeking Trial of the Clinical Benefit Rate Associated with Pamiparib in Subjects with Germline or Somatic BRCA1/2 High Grade Serous Ovarian Cancer or carcinosarcoma who have progressed on P-gp substrate chemotherapy or PARP inhibitors with the Presence of an ABCB1 Fusion and the Absence of a BRCA1/2 Reversion

Inclusion

Inclusion Criteria - Pre Screening
1. Patient has provided written informed consent for pre-screening
2. Patient is able to comply with the study protocol and follow-up procedures, in the Investigator’s judgement
3. Patient is female aged a minimum of 18 years at time of consent
4. ECOG performance status 0-2
5. Patient has the ability to take oral medications without medical history of malabsorption or other chronic gastrointestinal disease, or other conditions that may harm compliance and/or absorption of the study agent
6. Patients with a histopathological diagnosis of HGSC or carcinosarcoma of the ovary (including primary peritoneal cancers and fallopian tube cancers) as defined by histological diagnosis and immunohistochemistry (IHC) and with a germline or somatic BRCA1/2 mutation:
• Mixed histologies are allowed provided that >80% of the primary tumour is a high grade serous ovarian carcinoma based on diagnostic pathology review and IHC profile
7. Patients with progressive disease defined by GCIG CA-125 and/or RECIST v1.1 criteria after 3 or more lines of chemotherapy or after progression on a P-gp substrate PARP inhibitor
• Patients may continue on treatment as per standard of care by their usual clinician while awaiting the results of pre-screening with no impact on usual care.
• Patients who have been treated with both substrate PARPi and substrate chemotherapy will be considered eligible for either cohort 1 or cohort 2 based on the therapy they have most recently progressed on (cohort 1 is progression on PARPi and cohort 2 is progression on chemotherapy)
8. Disease that is amenable to a biopsy and/or ascitic drainage
• Lesions intended to be biopsied should not be target lesions with the preference of the biopsy site having progressed on most recent imaging where clinically safe and feasible
9. Patient has a life expectancy > 12 weeks
10. Patient has consented to the collection and use of their fresh tumour biopsies and/or ascites samples

Inclusion Criteria - Main Study
1. Patient has provided written informed consent for the main PRECISE study
2. Patient continues to meet all pre-screening inclusion criteria
3. Patient has an ABCB1 fusion(s) and the absence of BRCA1/2 reversions
4. Patient has platinum sensitive or platinum resistant HGSC
• Patients who are refractory (progress during or within 4 weeks) to second or subsequent lines of platinum-based chemotherapy are eligible.
• Patients who are primary platinum refractory (progress during or within 4 weeks of first line chemotherapy) are considered ineligible.
5. Recurrent disease that is measurable according to RECIST v1.1 or evaluable disease using CA-125 according to GCIG criteria
6. Adequate haematologic and end-organ function, as defined by the following laboratory results (obtained within 7 days prior to registration to the main study:
• Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L
• Platelet count greater than or equal to 100 x 109/L
• Haemoglobin (Hb) greater than or equal to 90 g/L (greater than or equal to 28 days after growth factor support or transfusion)
• Estimated glomerular filtration rate greater than or equal to 30 mL/min/1.73 m2 by the Modification of Diet in Renal Disease study equation (MDRD STUDY EQ; www.mdrd.com)
• Total serum bilirubin less than or equal to 1.5 x upper limit of normal (ULN) or less than or equal to 4 x ULN, if Gilbert’s syndrome or if indirect bilirubin concentrations suggestive of extrahepatic source of elevation
• Aspartate and alanine aminotransferase (AST and ALT) less than or equal to 3 x upper limit of normal (ULN) or less than or equal to 5 x ULN for patients with liver metastases
7. Patients who are not pregnant
• Females of childbearing potential require a negative serum pregnancy test within 7 days prior to registration into the main study
8. Females of childbearing potential must practice highly effective methods of birth control for the duration of the study and for at least 6 months after last study drug.
9. Patients must have recovered to less than or equal to grade 1 from their treatment-related adverse event (AE) with the exception of alopecia and peripheral neuropathy.
10. A formalin-fixed paraffin embedded FFPE tumour block, representative of the patient’s primary disease is available.
• In cases where there is insufficient FFPE tumour, a discussion with the CPI must be had before registration into the main study.