Neoadjuvant chemotherapy combined with toripalimab for triple-negative breast cancer: A prospective, single-arm, multi-center study (NEOTORCH-BREAST02).

595 Background: Neoadjuvant de-escalation chemo-immunotherapy with abbreviated cycles remains unclear. We aimed to assess the efficacy and safety of toripalimab, a novel PD-1 antibody, combined with an abbreviated course of epirubicin–cyclophosphamide (2 cycles) followed by nab-paclitaxel (2 cycles), as a neoadjuvant regimen for early-stage TNBC patients. Methods: This phase II trial, conducted from 2024 to 2025, involved stage II–III TNBC. The neoadjuvant regimen included epirubicin, cyclophosphamide, and toripalimab for 2 cycles, followed by nab-paclitaxel and toripalimab for another 2 cycles. Patients achieving a pathological complete response (pCR) received up to 13 cycles of adjuvant toripalimab, while those with residual disease received additional chemotherapy and toripalimab. Whole-exome sequencing (WES) and circulating tumor DNA (ctDNA) monitoring were also performed. The primary endpoint was the total pCR (tpCR) rate (ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR; ypT0/is), residual cancer burden (RCB 0–1), objective response rate (ORR), and event-free survival. This trial was registered with ClinicalTrials.gov (NCT06682195). Results: As of January 20, 2026, 48 patients were enrolled, and 40 underwent surgery (median age: 48 years; 87.5% stage II). WES analysis in 37 patients identified BRCA1 mutations in 12 (32.4%). Baseline ctDNA was positive in 32 of 34 (94.1%) patients, and 24 (75%) achieved ctDNA negativity after neoadjuvant therapy. Among 40 surgical patients, tpCR, bpCR, RCB 0-I, and ORR rates were 55%, 60%, 70, and 92.5%, respectively. Subgroup analyses showed tpCR rates of 25% for CPS <1, 58.3% for CPS ≥1, 72.7% for CPS ≥10, and 80% for CPS ≥20. For TILs <10, tpCR was 25%, increasing to 66.6% for TILs ≥10, 82.3% for TILs ≥30, and 85.7% for TILs ≥50. Among BRCA1 mutation carriers, 75% achieved tpCR, and 62.5% of patients with ctDNA negativity also achieved tpCR. Grade ≥3 AEs occurred in 6 (15%) patients, most commonly vomiting (7.5%) and leukopenia (7.5%). Hypothyroidism was the most frequent immune-related AE (17.5%, all grade 1–2). Conclusions: Preliminary findings indicate that this 4 cycles de-escalation neoadjuvant strategy is effective and safe for early-stage TNBC, warranting further investigation in randomized trials. Clinical trial information: NCT06682195 . Response endpoints for the entire cohort (N = 40). Efficacy endpoint N (%) 95% CI(%) tpCR(ypT0/is, ypN0) 22(55.0) 38.5–70.4 bpCR(ypT0/is) 24(60.0) 43.3–75.0 Miller–Payne (MP) grades MP score 1 2 (5.0) 0.6-23.2 MP score 2 3 (7.5) 1.6-27.3 MP score 3 7 (17.5) 7.3-34.7 MP score 4 4 (10.0) 2.8-23.7 MP score 5 24 (60.0) 43.3.-75.0 Residual cancer burden (RCB) class RCB class 0–I 28(70.0) 53.3–83.4 RCB class II 6 (15.0) 5.7-31.9 RCB class III 6 (15.0) 5.7-31.9 Abbreviations: tpCR, total pathological complete response; bpCR, breast pathological complete response; CI, confidence interval.