Abstract 836: A phase Ib/II study of PARPi Mefuparib Hydrochloride (CVL218) in combination with PD-1 inhibitor plus chemotherapy in metastatic or recurrent triple-negative breast cancer (TNBC)

Abstract Background: BRCA 1 and /or BRAC 2 mutation accounts for about 15% of all TNBC and remains poor outcomes. Mefuparib hydrochloride (CVL218) is a second generation in PARPi with low hematological toxicity and high ability to cross the blood-brain barrier. This study is to explore efficacy and safety of CVL218 combined with PD-1antibody and paclitaxel nanoparticle albumin-bound in patients with TNBC who have failed previous first-line treatment. Methods: This open- labeled, phase Ib/II clinical study NCT06078670 explores efficacy and safety of three drugs combination . 500mg BID CVL218 was administered orally in combination with toripalimab 240 mg on Day 1 of every 21-day cycle and paclitaxel nanoparticle albumin-bound 125 mg/m2 on Day 1 of every 21-day cycle. Patients in cohort A were advanced TNBC with either CPS ≥ 1 or HRD gene pathogenic variants. Results: From July 2023 to 15 July 2024 data, 6 subjects were enrolled in Phase Ib and 5 subjects were enrolled in Phase II. In phase Ib, The RP2D of CVL218 was identified as 500 mg BID. The preliminary efficacy was perfomed every 6 weeks in the first half a year and then once every 12 weeks thereafter in both phase Ib and II by RECISTv 1.1. Among 11 patients, ORR was 72.7% (8 PR, 2 SD), and DCR (Disease Control Rate) was 90.9%. The most common Grade 3 or higher treatment-related AEs (TRAEs) were hepatic function injury (2.6%), adynamia (1.8%), creatinine increased (0.8%), neutrophils decreased (0.8%), white blood cell decreased (0.8%), exanthema (0.8%), and peripheral sensory nerve disorder (0.8%), No Grade 5 TRAE. A total of 9 treatment-related SAEs in 6 patients (54.5%) were observed, including 2 aspartate aminotransferase increased, 2 alanine aminotransferase increased, 1 creatinine increased, 1 liver function injury, 1 adynamia, 1 neutrophils decreased, 1 fever, and 1 ventricular premature beats. All these SAEs recovered after symptomatic treatment. Conclusion: CVL218 combined with PD-1 antibody and chemotherapy appears to be well tolerated and has good preliminary efficacy in TNBC patients. Citation Format: Jian Zhang, Rujiao Liu, Steve Shen. A phase Ib/II study of PARPi Mefuparib Hydrochloride (CVL218) in combination with PD-1 inhibitor plus chemotherapy in metastatic or recurrent triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 836.