A phase II clinical study of adebrelimab and bevacizumab combined with cisplatin/carboplatin in triple-negative breast cancer patients with brain metastases.

1018 Background: Brain metastases (BMs) of triple-negative breast cancer (TNBC) is a lethal disease often associated with a limited life span of approximately 6 months and local therapy is usually the first treatment choice due to lack of effective anti-tumor agents. Here reported a triplet, anti-PD-L1 (Adebrelimab, SHR-1316), bevacizumab plus cisplatin/carboplatin in BMs of triple negative breast cancer. Methods: This is a single center, single-arm, phase II clinical trial involving triple-negative breast cancer patients with active brain metastases. A total of 35 participants were administered a triplet treatment consisting of Adebrelimab, bevacizumab and cisplatin/carboplatin. Prior use of bevacizumab or anti-PD-1/PD-L1 was not allowed. Prior use of platinum was allowed only in cases with platinum-sensitive disease. The primary endpoint was the objective response rate in the central nervous system (CNS-ORR), and the secondary endpoints included the clinical benefit rate in CNS (CNS-CBR), progression-free survival (PFS), overall survival (OS), the first progression site and safety. Results: The data cutoff for this analysis was on December 20, 2024. A total of 35 patients enrolled in this study from August 2020 to October 2024. Among all patients, 42.9% (15/35) had neurological symptoms at baseline, and 80% (28/35) had not received any local treatment for their brain metastases. The median number of previous lines of therapy for metastatic disease was 2 (range 0-4), with 40% (14/35) patients having received a prior platinum agent. In the intention-to-treat population,which comprised patients who received at least one cycle of study treatment, the CNS-ORR was 77.1% (27/35), with 5 complete responses (CR), 22 partial responses (PR) and the confirmed CNS-ORR was 71.4%(25/35). Among the 23 patients who progressed, the brain was the site of first progression in 69.6% (16/23) of patients. The median PFS was 7.6 months (95%CI, 5.7-11.5), while CNS-PFS was 10 months (95%CI, 7.4-12.6), and median OS was 16 months (95%CI, 11.7 to not reached). Treatment-related adverse events (TRAEs) were reported in 100% (35/35) of patients, with the incidence of grade≥3 TRAEs being 48.6% (17/35), including neutropenia (8.6%, 3/35) and platelet count decreased (8.6%, 3/35). Adebrelimab related serious adverse events (SAEs) occurred in one patient (facial nerve disorder), no treatment-related deaths were reported. Conclusions: The triplet treatment of anti-PD-L1 Adebrelimab, bevacizumab and cisplatin/carboplatin, was the first regimen demonstrating a high intracranial anti-tumor activity, a prolonged CNS-PFS and OS with a good safety profile. Warranting further investigation in this highly aggressive disease. Clinical trial information: NCT04303988 .