Abstract PS1-10-28: Phase 1/2a trial of new generation PARP1-selective inhibitor saruparib + next generation selective ER degrader (SERD) camizestrant in patients (pts) with advanced/relapsed ER+/HER2-negative or low (HER2−) breast cancer (PETRA Module 6)

Abstract Background: Saruparib (AZD5305) is a highly selective, potent inhibitor and trapper of PARP1. Camizestrant is an oral next generation SERD and complete ER antagonist. PETRA (NCT04644068) is a Phase 1/2a, modular, open label, multicenter study of saruparib as monotherapy or in combination with anticancer agents in pts with advanced solid malignancies. We present safety and preliminary efficacy of saruparib + camizestrant in pts with advanced/relapsed ER+/HER2- breast cancer. Methods: Pts were aged ≥18 years with histologically/cytologically confirmed breast adenocarcinoma, a locally-documented ER+ and HER2- tumor and an ECOG PS 0/1. Pts were required to have recurrence or progression on ≥1 line of endocrine therapy, and were allowed ≤2 prior lines of chemotherapy in the advanced setting and ≤1 prior PARP inhibitor. Pts could receive prior CDK4/6 inhibitors or fulvestrant, but not oral SERDs. Pts received 60 mg saruparib + 75 mg camizestrant daily orally. The primary objective was assessment of safety and tolerability; secondary objectives included pharmacokinetic (PK) assessments and preliminary antitumor activity. Results: At data cutoff (Mar 31, 2025), 38 pts had received ≥1 dose of the combination. Median age was 56 years; median prior lines of therapy was 3.5 (range, 1-13). BRCA1/BRCA2 mutation (m) and PALB2m were detected in 8 (21.1%) and 2 (5.3%) pts, respectively, based on local testing. Safety is summarized in the Table. Hematological toxicities included anemia and neutropenia; gastrointestinal toxicities included nausea and vomiting. PK data showed no evidence of drug interaction between saruparib and camizestrant. Saruparib exposure was comparable following single-dose saruparib versus saruparib at steady-state in combination with camizestrant, for AUC (42,219 vs 41,703 h*ng/mL) and Cmax (2,834 vs 3,250 ng/mL). Eight of 35 evaluable pts achieved confirmed partial responses (by RECIST v1.1) for an objective response rate (ORR) of 22.9%; median duration of response was 5.5 months. In addition, 12 pts (34.3%) achieved stable disease for a disease control rate of 57.1%. An ORR of 33.3% was reported in 9 pts with measurable disease and BRCA1/BRCA2m or PALB2m. The median progression-free survival was 4.4 months (80% CI, 2.0-5.6) overall and 6.1 months (80% CI, 4.4-7.3) in pts with mutations. Conclusion: Saruparib + camizestrant was well tolerated with no new safety signals versus prior monotherapy studies of each drug. PK of saruparib in combination with camizestrant was consistent with monotherapy data. Preliminary efficacy of the combination was promising and compared favorably with camizestrant monotherapy. This combination is being tested in a randomized Phase 3 trial in pts with ER+/HER2- and BRCA1m/BRCA2m or PALB2m (EvoPAR-Breast01; NCT06380751). Citation Format: T. A. Yap, K. Yonemori, W. Li, S. Kitano, F. Lynce, A. Sharp, A. Falcón, J. Garcia-Corbacho, R. D. Baird, J. Balmaña, S. Nanda, I. Song, K. Sugibayashi, L. Womersley, M. Squatrito, E. Gangl, T. Milenkova, S. J. Luen. Phase 1/2a trial of new generation PARP1-selective inhibitor saruparib + next generation selective ER degrader (SERD) camizestrant in patients (pts) with advanced/relapsed ER+/HER2-negative or low (HER2−) breast cancer (PETRA Module 6) abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-28.