Pamiparib Plus Surufatinib Shows Modest Activity in Platinum-Resistant Ovarian Cancer

The combination of pamiparib and surufatinib elicited responses with the potential for enrichment according to circulating tumor DNA (ctDNA) assessment in patients with platinum-resistant ovarian cancer who received prior PARP inhibitors, according to data from the single-arm, phase 1b/2 POST-PARPi trial (NCT05494580) presented during the 2025 SGO Annual Meeting on Women’s Cancer.

At a data cutoff of June 20, 2024, and median follow-up of 7.3 months (range, 1.0-18.1), the 6-month progression-free survival (PFS) rate was 46.7% (95% CI, 24.4%-66.2%). The median overall survival (OS) was 14.7 months (95% CI, 9.9-not evaluable).

The objective response rate (ORR) among the overall population (n = 29) was 6.9% (95% CI, 0.8%-22.8%). Best responses were partial response (PR; n = 2), stable disease (n = 20), and progressive disease (n = 3) for a disease control rate (DCR) of 69% (95% CI, 49.2%-84.7%). Four patients were not evaluable.

“The combination of pamiparib and surufatinib demonstrated modest yet clinically meaningful antitumor activity with manageable toxicities in patients with platinum-resistant ovarian cancer who had progressed on or after prior PARP inhibitor treatment,” lead study author Chunyan Lan, MD, PhD, of the Department of Gynecologic Oncology at Sun Yat-sen University Cancer Center in Guangzhou, China, and coauthors, wrote in the poster presentation.

PARP inhibitors have become a standard part of frontline maintenance therapy for patients with advanced ovarian cancer. Despite improved outcomes with these agents, many patients still develop resistance, leaving investigators in search of novel regimens. This served as the basis for the multicenter trial.

To be eligible for enrollment patients had to have platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer with disease progression on or after prior PARP inhibitors. Measurable lesions according to RECIST 1.1 criteria were also required.

In phase 1b, patients received either 250 mg (dose level 1) or 200 mg (dose level 2) of surufatinib once daily in combination with 40 mg of pamiparib twice daily in continuous 21-day cycles. In phase 2, patients received the recommended phase 2 dose of surufatinib, 250 mg, plus pamiparib.

Patients were enrolled between September 22, 2022, and November 4, 2023. Three patients were enrolled in the phase 1b portion and 26 in the phase 2 portion. All patients received 250 mg of surufatinib once daily plus 40 mg of pamiparib twice daily. No dose-limiting toxicities occurred in either population. All 3 patients in phase 1b had discontinued treatment due to disease progression (n = 1), an adverse effect (AE; n = 1), and COVID-19 (n = 1). Most patients in phase 2 had discontinued treatment (n = 24) due to disease progression (n = 15), consent withdrawal (n = 2), AEs (n = 2), patient refusal (n = 3), and COVID-19 (n = 2).

All 29 patients were included in the full analysis and safety analysis sets. Four patients discontinued treatment before the first post-baseline tumor assessment and were excluded from the efficacy-evaluable set (n = 25).

The primary end point was the 6-month PFS rate. Secondary end points included ORR, DCR, and OS. The association between ctDNA and clinical outcomes was evaluated as an exploratory end point. ctDNA PR was defined as a decrease in ctDNA in accordance with the Liquid Biopsy Response Assessment Criteria for Solid Tumors.

The median age within the full analysis set was 54 years (range, 31-69). FIGO stage at diagnosis was IC1 (n = 1; 3.4%), IIB (n = 1; 3.4%), IIIA1 (n = 1; 3.4%), IIIC (n = 15; 51.7%), and IVB (n = 11; 37.9%). Histologic subtype at diagnosis was high-grade serous carcinoma (n = 27; 93.1%), clear cell (n = 1; 3.4%), and carcinosarcoma (n = 1; 3.4%). ECOG performance status was 0 (n = 3; 10.3%) or 1 (n = 26; 89.7%) and the median number of prior lines of systemic therapy was 3. Most patients had received 3 or 4 prior lines of treatment (n = 19; 65.5%) as opposed to 1 or 2 (n = 10; 34.5%).

The median treatment-free interval (TFI) was 1.2 months (range, 0.6-5.8). Most patients had a TFI of less than 3 months (n = 25; 86.2%) vs between 3 and 6 months (n = 4; 13.8%). The median platinum-free interval was 5.2 months (range, 0.9-38.0) but was stratified according to an interval of less than 3 months (n = 9; 31.0%), between 3 and 6 months (n = 8; 27.6%), and greater than 6 months (n = 12; 41.4%).

Prior PARP inhibitor therapy included olaparib (Lynparza; n = 14; 48.3%), niraparib (Zejula; n = 15; 51.7%), fluzoparib (n = 1; 3.4%), and IMP4297 (n = 1; 3.4%). The median duration of prior PARP inhibitor treatment was 5.1 months (range, 1.6-37.7) but ranged from less than 6 months (n = 17; 58.6%), to between 6 and 12 months (n = 5; 17.2%), and greater than 12 months (n = 7; 24.1%).

With respect to safety, grade 3 or 4 treatment-related adverse effects (TRAEs) occurred in 37.9% (n = 11) of patients. The most frequent grade 3/4 TRAEs were thrombocytopenia (n = 6; 20.7%), anemia (n = 5; 17.2%), and neutropenia (n = 4; 13.8%).

Furthermore, ctDNA concentrations were significantly higher in patients whose disease progressed within 6 months (P =.011). Notably, median PFS was 7.82 months in patients who had a ctDNA PR by day 1 of cycle 3 vs 3.52 months in those who did not achieve a response at that time (P =.05). Median PFS was 9.46 months and 3.83 months in patients who achieved a ctDNA PR by day 1 of cycle 7 vs those who did not, respectively.

“Our findings also highlight the potential of ctDNA as a valuable tool for predicting treatment outcomes in this challenging setting, [but] further validation in larger studies is necessary,” the authors concluded.

Reference

Lan C, Li J, Huang X, et al. Pamiparib in combination with surufatinib in patients with platinum-resistant ovarian cancer who received prior PARP inhibitors: a multicenter, single-arm, phase Ib/II trial (POST-PARPi trial). Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 859742.