A randomized phase II study of pembrolizumab plus paclitaxel with or without bevacizumab in PD-L1–positive recurrent triple-negative breast cancer previously treated with perioperative immune checkpoint inhibitors: WJOG16522B (PRELUDE) trial.

TPS1163 Background: Perioperative pembrolizumab combined with chemotherapy has become a standard of care for patients with early-stage triple-negative breast cancer (TNBC). However, a substantial proportion of patients experience disease recurrence after perioperative immune checkpoint inhibitor (ICI)–based therapy, and the optimal systemic treatment for this population remains undefined. Angiogenesis has been implicated as a potential mechanism of resistance to immunotherapy. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), may enhance antitumor immunity through vascular normalization and modulation of the tumor microenvironment. The PRELUDE trial was designed to evaluate whether the addition of bevacizumab to pembrolizumab plus paclitaxel improves clinical outcomes in patients with PD-L1–positive recurrent TNBC previously treated with perioperative ICIs. Methods: PRELUDE is a multicenter, open-label, randomized phase II trial conducted in Japan. Eligible patients have recurrent TNBC with PD-L1 expression (combined positive score ≥10 using 22C3) and prior exposure to perioperative ICI-containing chemotherapy. Patients are randomized 1:1 to receive pembrolizumab plus paclitaxel with or without bevacizumab. Pembrolizumab is administered at 400 mg every 6 weeks, paclitaxel at 90 mg/m² on days 1, 8, and 15 every 4 weeks, and bevacizumab at 10 mg/kg on days 1 and 15 every 4 weeks in the experimental arm. Treatment is continued until disease progression or unacceptable toxicity. Tumor assessments are performed according to RECIST v1.1. Exploratory biomarker analyses using tumor tissue and peripheral blood samples are planned. The primary endpoint is progression-free survival. Secondary endpoints include overall response rate, disease control rate, overall survival, and safety. Exploratory endpoints include translational biomarker analyses to investigate mechanisms of response and resistance. Enrollment is currently ongoing. ClinicalTrials.gov: NCT06976944, jRCT2031250076.