pamiparib plus surufatinib in patients with platinum-resistant ovarian cancer

Conditions: Ovarian Cancer; Ovarian Carcinoma; Platinum-resistant Ovarian Cancer; Fallopian Tube Carcinosarcoma; Primary Peritoneal Cancer

Summary: a number of studies suggest that the combination of parp inhibitors and antiangiogenic agents produce synergistic activities. pamiparib is a small molecule inhibitor selectivity for both parp1 and parp2. surufatinib is a novel small-molecule inhibitor that simultaneously targets tumor angiogenesis (via vascular endothelial growth factor receptor \[vegfr\]1, vegfr 2, vegfr3 and fibroblast growth factor receptor 1 \[fgfr1\]) and immune evasion (via colony stimulating factor 1 receptor \[csf1r\]). in this trial, we aimed to evaluate the efficacy, safety and tolerability of pamiparib in combination with surufatinib in patients with platinum-resistant ovarian cancer who received prior parp inhibitors.


Eligibility criteria:
inclusion criteria: 1. signed informed consent form; 2. histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; 3. platinum-resistant disease, defined as progression within 6 months from completion of most recent platinum-containing therapy. subject may have been treated with additional regimen(s) subsequent to determination of platinum resistance; 4. patients must have received one prior parp inhibitor therapy, and there must be a ≥ 6 month interval since treatment; 5. female participants age 18-75 years; 6. has measurable lesion per recist v1.1; 7. eastern cooperative oncology group (ecog) performance status of 0 or 1; 8. life expectancy ≥ 3 months; 9. patients must have normal organ and bone marrow function; 10. women of childbearing potential should have a negative serum or urine pregnancy test prior to receiving the first dose of study treatment; and should be willing to use one acceptable contraception (i.e., oral contraceptives, condoms, intrauterine devices \[iuds\]) throughout the period of taking study treatment and for at least 6 months after the last dose of study drug(s). exclusion criteria: 1. histological diagnosis of mucinous adenocarcinoma; 2. has received prior therapy with small molecule antiangiogenic receptor tyrosine kinase inhibitors (tkis); 3. known or suspected allergy to any of study drugs; 4. has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including new york heart association \[nyha\] class \> 2, unstable angina, myocardial infarction, cardiac arrhythmia associated with hemodynamic instability (including corrected qt (qtc) interval ≥ 450 ms in men, ≥ 470 ms in female); 5. has active ulcers, gastrointestinal perforation or obstruction; 6. active bleeding or pathologic condition that carries a high risk of bleeding; 7. inadequately controlled hypertension (systolic blood pressure ≥ 150 mmhg and/or diastolic blood pressure ≥ 90 mmhg) with or without treatment; 8. major surgery within 28 days of starting study treatment; 9. proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g; 10. uncontrolled pericardial or pleural or peritoneal effusions; 11. has a diagnosed and/or treated additional malignancy within the last 5 years. exceptions include in situ cervical cancer, non-melanoma skin cancer, or superficial bladder tumors that has undergone potentially curative therapy; 12. known human immunodeficiency virus (hiv) infection; 13. has known active central nervous system (cns) metastases and/or carcinomatous meningitis; 14. any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study.

Keywords: ovarian cancer parp inhibitor antiangiogenic agents platinum-resistant