Capivasertib plus fulvestrant in Chinese patients with HR+/HER2− advanced breast cancer: Interim analysis of CAPItrue.

Abstract

1088 Background: After disease progression on cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET), patients (pts) with HR+/HER2- advanced breast cancer (ABC) face limited treatment options and poor prognosis, particularly those with PI3K/AKT pathway tumor alterations, which are major drivers of disease progression and treatment resistance mediated centrally by AKT. Targeting the PI3K/AKT pathway represents a mechanism-driven precision strategy to overcome CDK4/6i/ET resistance, with potential to maximize ET benefit and delay subsequent chemotherapy. In the phase III CAPItello-291 trial, capivasertib (CAPI) plus fulvestrant (FUL) improved progression free survival (7.3 vs 3.1 months, HR 0.50) versus placebo plus FUL in pts with PIK3CA/AKT1/PTEN -altered tumors. CAPItrue (NCT06635447) is an ongoing phase IIIb study of CAPI plus FUL in Chinese pts with HR+/HER2- ABC progressing on ET, with a focus on PIK3CA/AKT1/PTEN-altered disease, aiming to inform precision 2 nd line treatment following CDK4/6i progression. Methods: CAPItrue enrolled Chinese pts with HR+/HER2- ABC progressing on ET±CDK4/6i. All pts received oral CAPI (400 mg BID, 4 days on, 3 days off) and intramuscular FUL. This pre-specified interim analysis was performed in the cohort (C1) without prior FUL (conducted after the last C1 pt received ≥1 dose of study treatment). Baseline characteristics, biomarker profiles, preliminary efficacy (interim objective response rate [ORR] was evaluated in pts with ≥4 months of follow-up) and safety were summarized. Results: By Aug 20, 2025, 195 pts were enrolled in C1 and received study treatment. PIK3CA/AKT1/PTEN alterations were detected in 115 (59.0%) pts (altered group). The median age was 55.0 yrs; 64.1% were post-menopausal. Prior therapy for ABC included: 75.4%/8.7% 1/2 prior lines of ET; 65.1% CDK4/6i, 17.9% chemotherapy. The altered group showed similar characteristics. In patients with ≥4 months of follow-up, ORR was 35.6% overall (37/104, 1 complete and 36 partial responses [PR]) and 43.1% in the altered group (25/58, 25 PR). Overall, at a median follow-up of 4.1 months,92.8% had ≥1 adverse event (AE); 88.7% had AEs possibly related to CAPI; and 34.9%/11.8% had grade ≥3/serious AEs (SAE). A similar safety profile was seen in the altered group (any AE: 92.2%, grade ≥3 AE: 30.4%, SAE: 11.3%). No new safety signal was observed. Conclusions: In Chinese pts with PIK3CA/AKT1/PTEN -altered HR+/HER2- ABC previously treated with ET±CDK4/6i, CAPI plus FUL showed encouraging preliminary efficacy and safety. Follow-up is ongoing. Clinical trial information: NCT06635447 .