PLD + Pembrolizumab (Anthracycline/PD-1) Delivers 33% ORR in ER+ MBC

PEG-liposomal doxorubicin (PLD), an anthracycline formulation that may induce immunogenic cell death, was combined with pembrolizumab PD-1 blockade in a Phase 1b trial of ER+/HER2− metastatic breast cancer after endocrine therapy, CDK4/6 inhibitors, and up to 3 prior chemotherapy lines (n=35; response-evaluable n=30; NCT03591276). Across two PLD schedules with pembrolizumab 200 mg every 3 weeks, ORR was 33% with 8 PRs and 2 CRs, median DoR was 11 months, and median OS was 25 months overall and 26 months in evaluable patients. Safety included immune-mediated grade 4 hepatitis (n=2) and grade 4 hemolytic anemia (n=1), with no grade 3–4 neutropenia or cardiac events; the 33% ORR is above pembrolizumab monotherapy’s ~12% ORR in PD-L1+ ER+/HER2− disease and sits favorably against later-line HR+/HER2− options such as TROPiCS-02, where sacituzumab improved median OS to 14.4 vs 11.2 months over physician’s-choice chemotherapy.