Neoadjuvant penpulimab combined with taxanes and carboplatin in triple-negative breast cancer: Updated efficacy and safety results from the phase II NeoTAPPL study.

600 Background: The KEYNOTE-522 and IMpassion031 trials established that adding immune checkpoint inhibitors to neoadjuvant chemotherapy significantly improves pathologic complete response (pCR) rates and survival outcomes in triple-negative breast cancer (TNBC). In our previously reported phase II NeoTAPPL trial, an anthracycline-free neoadjuvant regimen of penpulimab (anti-PD-1 antibody), carboplatin, and taxanes demonstrated promising efficacy and manageable safety. Here, we present updated efficacy and safety outcomes from the full trial cohort. Methods: In this open-label, multi-center phase II study, patients with untreated, histologically confirmed TNBC in stage II-III were enrolled. Patients received 6 cycles of neoadjuvant therapy with penpulimab (200 mg, d1, q3w) plus taxanes (docetaxel 75 mg/m2 or nab-paclitaxel 260 mg/m2, d1, q3w) and carboplatin (AUC=6, d1, q3w). Patients who either completed or discontinued the neoadjuvant treatment would undergo breast surgery. Adjuvant chemotherapy and immunotherapy were at the discretion of the treating physician, and radiation therapy was per standard of care. The primary endpoint was the rate of pCR based on the definition of ypT0/Tis ypN0. Secondary endpoints included residual cancer burden (RCB), event free survival (EFS), overall survival (OS), adverse events (AE), and immune response biomarkers. Results: 64 patients were enrolled, all of whom received neoadjuvant treatment and underwent surgery. The median age was 53 years (range, 32-73). At diagnosis, 54 patients (84.4%) had stage II disease. pCR was achieved in 41 of 64 patients (64.1%; 95% CI, 51.1%-75.7%), and 50 patients (78.1%; 95% CI, 66.0%-87.5%) achieved RCB 0-1. The objective response rate (ORR) and disease control rate (DCR) were 93.8% (95% CI, 84.8%-98.3%) and 98.4% (95% CI, 91.6%-100%), respectively. Subgroup analyses revealed pCR rates of 64.8% (35/54) in patients with stage II disease and 60.0% (6/10) in those with stage III disease. The pCR rate was 64.9% (24/37) in node-negative patients and 63.0% (17/27) in node-positive patients. Treatment-emergent adverse events (TEAEs) of any grade occurred in all 64 patients, with grade ≥3 TEAEs reported in 24 patients (37.5%). The most common grade ≥3 TEAEs were alopecia (20.3%), anemia (14.1%), neutropenia (10.9%), and leukopenia (10.9%). Conclusions: The NeoTAPPL trial demonstrates that an anthracycline-free neoadjuvant regimen is an effective and tolerable treatment strategy for patients with TNBC. The regimen achieved a high pCR rate, which remained consistent across key prognostic subgroups, including disease stage and nodal status. The safety profile was manageable, with no new safety signals identified. Clinical trial information: ChiCTR2300071925 .