A phase II study combining radiotherapy and atezolizumab/nab-paclitaxel for inoperable or recurrent programmed death-ligand 1-positive triple-negative breast cancer: IMRad-Br study protocol and safety run-in

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expressions, with poor prognosis and limited treatment options. Studies have demonstrated the efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in patients with programmed death-ligand 1 (PD-L1)-positive advanced TNBC. Radiotherapy (RT) may enhance therapeutic effects when combined with ICIs. In this ongoing single-arm, multicenter phase II trial (IMRad-Br; jRCTs021210010), we aimed to evaluate the safety and feasibility of combining atezolizumab/nab-paclitaxel with local RT in patients with inoperable or recurrent PD-L1-positive TNBC. Patients received atezolizumab (840 mg on days 1 and 15 of a 28-day cycle) and nab-paclitaxel (100 mg/m 2 on days 1, 8, and 15), followed by local RT at 30 Gy in five fractions. A safety run-in was conducted in six evaluable patients to assess protocol-defined prespecified adverse events of interest (PAEIs). Among the seven patients enrolled, one PAEI was observed (grade 4 liver injury), which improved with treatment interruption and follow-up. Two additional serious adverse events occurred but were unrelated to the study treatment. No unexpected toxicity was observed. Combination therapy was deemed feasible by an Independent Data Monitoring Committee. The combination of atezolizumab/nab-paclitaxel with local RT was feasible and did not result in unexpected toxicities during the safety run-in phase. This study is ongoing to evaluate the safety and therapeutic potential of ICI–RT combination therapy for recurrent PD-L1-positive TNBC. The final analysis will determine whether this approach merits broader clinical adoption.