LBA36 - Efficacy and safety of senaparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer (FLAMES study): A randomized, double-blind, placebo-controlled, phase III trial

Background

Ovarian cancer (OC) is one of the most lethal gynecologic cancers. Approximately 85% of newly diagnosed advanced OC may experience a relapse after the first line (1L) platinum-based chemotherapy. PARP inhibitors are recommended as maintenance therapy to prolong the benefit of platinum. Senaparib (IMP4297) is a novel, highly potency PARP inhibitor. The phase 3 study FLAMES is to investigate the efficacy and safety of Senaparib in Chinese patients (pts) with newly diagnosed advanced OC as 1L maintenance therapy.

Methods

Eligible pts had newly diagnosed, FIGO stage III–IV, high-grade serous or endometrioid OC, who have completed 1L platinum-based chemotherapy with complete response (CR) or partial response (PR). Pts were randomized (2:1) to receive senaparib (Sena) or placebo (PBO) 100 mg/day orally, stratified by CR/PR and BRCA mutation positive/negative. Primary endpoint was progression-free survival (PFS ) evaluated by blinded independent central review (BICR) according to RECIST v1.1.

Results

404 pts were randomized. As of 16 Mar. 2023, 270 and 133 pts received Sena and PBO with a median follow-up of 22.4 and 22.2 months, respectively. Primary analysis showed Sena significantly improved PFS over placebo (HR 0.43, 95% CI 0.32-0.58, P < 0.0001), irrespective of BRCA mutation status ( HR 0.43, P < 0.01). Secondary endpoints support the primary analysis (Table). Incidence rates of grade ≥3 adverse events (AEs) were 66.3 % vs 20.3%, AEs leading to dose reduction 63.3 % vs 6.0% and discontinuation 4.4 % vs 0% in Sena and PBO arm. No AE leading to death. Table: LBA36

BICR, blinded independent central review; INVR, investigator review; HR, hazard ratio; NR, not reached; PFS, progression-free survival; BRCA +, breast cancer susceptibility gene (BRCA) mutation positive; BRCA -, BRCA mutation negative; TFST, time to first subsequent therapy or death; m, month

Conclusions

1L maintenance Senaparib led to an unprecedented reduction in the risk of progression or death versus placebo in OC, regardless of biomarker status. Senaparib was well tolerated, no new safety signals were identified.

Clinical trial identification

NCT04169997.

Editorial acknowledgement

Legal entity responsible for the study

IMPACT Therapeutics, Inc.

Funding

IMPACT Therapeutics, Inc.

Disclosure

All authors have declared no conflicts of interest.