KEY TAKEAWAYS
- The POST-PARPi phase 1 and 2 trials aimed to investigate the synergistic effects of combining the PARP inhibitor pamiparib with surufatinib in platinum-resistant OC patients.
- The primary endpoint was to determine the MTD.
- Researchers noticed significant antitumor activity with manageable safety in heavily pretreated platinum-resistant OC patients receiving the pamiparib and surufatinib combination.
Several studies suggest that combining PARP inhibitors (PARPi) with antiangiogenic agents may exhibit synergistic effects.
Chunyan Lan and the team aimed to assess the findings from a phase 1b/2 trial investigating the efficacy of the PARPi pamiparib in combination with surufatinib, a novel small-molecule inhibitor targeting both tumor angiogenesis and immune evasion, in patients with platinum-resistant ovarian cancer (OC) who had previously received PARPi therapy.
Researchers performed an inclusive analysis, enrolling eligible patients with platinum-resistant OC previously treated with PARPi, irrespective of biomarker status. The phase 1b utilized a 3+3 dose de-escalation design to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of surufatinib in combination with pamiparib.
Subsequently, approximately 26 patients were enrolled in a phase 2 expansion cohort and treated at the RP2D, with the primary endpoint being the 6-month rates of progression-free survival (PFS). Key secondary endpoints comprised objective response rate (ORR), PFS, overall survival (OS), and safety assessment.
About 24 patients were enrolled between Sep 22, 2022, and Sep 21, 2023 (three in phase 1b; 21 in phase 2). Enrollment was ongoing as of the data cutoff on Sep 29, 2023. Among them, 17 patients (70.8%) had received ≥3 previous lines of therapy, and 4 patients (16.7%) had germline mutations in BRCA1. No dose-limiting toxicities (DLTs) were observed in phase 1b. The MTD and RP2D were determined as pamiparib 40 mg, P.O. bid, and surufatinib 250 mg, P.O. qd, given in each 21-day cycle.
The 6-month rates of PFS were 60.0% (95% CI: 28.1–81.4). Additionally, two patients (11.1%; 95% CI: 1.4–34.7) achieved partial responses, with a median PFS of 7.5 months (95% CI: 3.4–not evaluable). Grade ≥3 adverse events (AEs) occurred in 37.5% of patients, with neutropenia (n=5, 20.8%), anemia (n=4,16.7%), and thrombocytopenia (n=3, 12.5%) being the most common.
The study concluded that the combination of pamiparib and surufatinib demonstrates clinically significant antitumor activity in heavily pretreated platinum-resistant ovarian cancer patients who had previously received PARPi therapy. Furthermore, the safety profile of this combination was found to be manageable, particularly in patients undergoing PARPi retreatment.
The trial was sponsored by Sun Yat-sen University
Source: https://sgo.planion.com/Web.User/AbstractDet?ACCOUNT=SGO&ABSID=458846&CONF=AM2024&CKEY=
Clinical Trial: https://clinicaltrials.gov/study/NCT05494580
Lan C, Li J, Lian S, et al. (2024). “Pamiparib in combination with surufatinib among patients with platinum-resistant ovarian cancer who received prior PARP inhibitors: A multicenter, single-arm, phase Ib/II trial (POST-PARPi Trial).” Presented at SGO 2024.
