Phase 2 DETENTE-1 tests pembrolizumab PD‑1 inhibitor with/without carbo‑taxane neoadjuvant therapy.

UT Southwestern’s Phase 2 randomized pilot study (DETENTE-1) evaluates whether tailoring neoadjuvant therapy can increase pathologic complete response (pCR) in treatment-naive stage I TNBC (T1a–T1c, M0) before surgery. Patients are randomized to pembrolizumab alone, paclitaxel + carboplatin, or the triplet pembrolizumab + paclitaxel + carboplatin; pembrolizumab (Merck/MSD) is a PD‑1 (CD279)–blocking monoclonal antibody that restores antitumor T-cell activity, while paclitaxel disrupts microtubules to block cell division and carboplatin forms DNA crosslinks that impair DNA replication. The key scientific angle is de-escalation vs escalation in small, node-negative TNBC—testing whether some patients can achieve pCR with less chemotherapy, or whether early chemoimmunotherapy is needed even at stage I. Today’s care for stage I TNBC is upfront surgery with adjuvant taxane-based chemotherapy for higher-risk T1c disease (and often observation for many T1a tumors), whereas pembrolizumab-based neoadjuvant regimens are generally reserved for higher-risk early TNBC; this trial probes whether that boundary should move.