766P - A phase II trial of fuzuloparib in combination with apatinib vs. fuzuloparib alone for recurrent ovarian cancer (OC)

Background

The combination of a PARP inhibitor with an anti-angiogenic agent has demonstrated improved clinical outcomes as a treatment for recurrent OC. We conducted a randomized, controlled, open-label, multi-center, phase 2 trial to assess fuzuloparib (FZPL, a PARP inhibitor) plus apatinib (APA, a VEGFR2 inhibitor) vs. FZPL alone in patients (pts) with recurrent OC.

Methods

Pts with recurrent OC who had failed ≥ 2 prior lines of platinum-based chemo were enrolled. Pts with primary platinum resistance (defined as progression/relapse within >1 to <6 mo after 1st-line platinum-based chemo) were also eligible. No prior PARP inhibitors were allowed. Pts were randomized 1:1 to receive FZPL (100 mg PO BID) plus APA (500 mg PO QD) or FZPL (150 mg PO BID). Stratification factors were gBRCA1/2 mutation (yes vs. no) and time from the last platinum-based chemo to progression/relapse (>1 to <6 mo [platinum-resistant] vs. ≥ 6 to <12 mo [platinum-sensitive]). The primary endpoint was ORR.

Results

As of Jan 11, 2024, 76 pts were enrolled (39 with FZPL plus APA and 37 with FZPL). ORR was 38.5% (95% CI: 23.4, 55.4) with FZPL plus APA and 35.1% (95% CI: 20.2, 52.5) with FZPL; DCR was 87.2% (95% CI: 72.6, 95.7) and 73.0% (95% CI: 55.9, 86.2); median DoR was 9.2 mo (95% CI: 3.7, 14.8) and 6.5 mo (95% CI: 3.7, 9.2) (HR=0.56; 95% CI: 0.2, 1.5); median PFS was 7.3 mo (95% CI: 4.9, 9.2) and 5.5 mo (95% CI: 3.7, 8.3) (HR=0.70; 95% CI: 0.4, 1.2). ORR was 29.6% with FZPL plus APA and 20.0% with FZPL in pts with platinum-resistant OC, and ORR was 50.0% and 36.7% in pts without prior VEGFR inhibitors (table). Grade 3/4 treatment-related AEs occurred in 61.5% and 40.5% of pts in FZPL plus APA and FZPL groups, with the most common being anemia (15.4%, 32.4%), hypertension (12.8%, 0), and decreased platelet count (10.3%, 21.6%). No treatment-related death was reported. Table: 766P

Subgroup analyses of ORR

Data are % (n/N; 95% CI) unless otherwise stated.

Conclusions

FZPL plus APA vs. FZPL showed a trend of improved ORR in OC pts with platinum resistance or without prior VEGFR inhibitors.

Clinical trial identification

NCT04517357.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

J. Lin, Y. Wang: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd.. All other authors have declared no conflicts of interest.