Multicenter phase 1b-2 trial of first-line pumitamig plus nab-paclitaxel for triple-negative breast cancer

Pumitamig is an investigational bispecific antibody targeting PD-L1 and VEGF-A. A phase 1b-2 trial at ten centers in China evaluated the combination of pumitamig and nab-paclitaxel as first-line treatment for patients with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC). Patients aged 18-75 years with an ECOG performance status 0 or 1 received first-line pumitamig (20 mg/kg every 2 weeks) plus nab-paclictxel (100 mg/m² on days 1, 8, and 15 of 28-day cycles) until disease progression or unacceptable toxicity. In phase 1b, six patients were monitored for adverse events before subsequent enrollment in phase 2. The primary endpoints were confirmed objective response rate (cORR) and safety. A total of 42 evaluable patients were enrolled. Median duration of treatment was 9.0 months (95% CI 6.9-11.7). At a median follow-up of 35.2 months (95% CI 33.0-36.1), the cORR was 73.8% (95% CI 58.0-86.1), including one complete response and 30 partial responses. The most frequent treatment-related adverse events (TRAEs) of grade 3 or higher were decreased neutrophil count (31% of patients), decreased white blood cell count (26%), proteinuria (14%), and febrile neutropenia (12%). Nine patients (21%) reported 14 treatment-related serious adverse events. TRAEs led to discontinuation of both drugs in four patients (10%), of nab-paclitaxel in three patients (7%), and of pumitamig in two patients (5%). There were no treatment-related deaths. The authors conclude that first-line pumitamig plus nab-paclitaxel showed encouraging antitumor activity in patients with advanced or metastatic TNBC and a safety profile consistent with mode of action of both agents.