Phase 2 pembrolizumab PD‑1 inhibitor with anthracycline-sparing neoadjuvant chemo in high‑TIL TNBC

This Phase 2 NeoTILs study from the Medical University of South Carolina (MUSC) tests a biomarker-guided de-escalation strategy in stage II–IIIB triple-negative or hormone receptor–low (ER/PR <10%) invasive breast cancer with pathologist-assessed high tumor-infiltrating lymphocytes (TILs), a subgroup that tends to be more chemo- and immunotherapy-responsive. Everyone starts with 12 weeks of anthracycline-free neoadjuvant carboplatin (platinum DNA crosslinker) + paclitaxel (microtubule/tubulin inhibitor) plus pembrolizumab (Merck/MSD; PD‑1–blocking monoclonal antibody), then proceeds to surgery. Post-op therapy is response-adapted: patients with pathologic complete response continue pembrolizumab maintenance, while those with residual disease are escalated to anthracycline/cyclophosphamide plus pembrolizumab, aligning closer to current intensification strategies. The key angle is sparing anthracyclines up front (reducing cardiomyopathy and rare therapy-related myeloid neoplasms risk) while preserving a “rescue” escalation path for non-pCR patients; today’s common approach for higher-risk early TNBC is neoadjuvant multi-agent chemotherapy including an anthracycline/taxane backbone plus pembrolizumab, followed by additional post-op systemic therapy tailored to residual disease and biomarkers.