Neoadjuvant penpulimab combined with taxanes and carboplatin in triple-negative breast cancer: A single-arm, open-label, multi-center phase II clinical study (neoTAPPL).

588 Background: The integration of immunotherapy with neoadjuvant chemotherapy has been shown to enhance pathologic complete response (pCR) and survival outcomes in patients with triple-negative breast cancer (TNBC). Nonetheless, additional research is required to ascertain the optimal neoadjuvant regimen. Here we present a prospective phase II NeoTAPPL trial in which evaluated the efficacy and safety of penpulimab (anti-PD-1 antibody) in combination with taxanes and carboplatin for TNBC patients. 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/m 2 or nab-paclitaxel 260 mg/m 2 , 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: 50 patients were enrolled, among which 37 patients received neoadjuvant treatment and underwent breast surgery. The median age was 51 years (range, 32-72). 33 (89.2%) patients had stage II breast cancer at diagnosis. 21 of the 37 patients achieved pCR (56.7%; 95% CI, 40.9%-71.3%), and 29 patients achieved RCB 0-1 (78.4%; 95% CI, 62.8%-88.6%). The ORR and DCR were 86.5% (95% CI, 72.0%-94.1%) and 91.9% (95% CI, 78.7%-97.2%), respectively. Subgroup analysis showed that 60.6% (20/33) patients with stage II had achieved pCR, 25% (1/4) patients with stage III reached this outcome. The pCR rate was 56.5% (13/23) in patients with negative lymph nodes, and 57.1% (8/14) in those with positive lymph nodes. Treatment-emergent adverse events (TEAEs) of any grade occurred in all 37 pts, in which 20 (54.1%) were grade ≥3. The most common grade ≥3 TEAEs were neutropenia (43.2%), leukopenia (24.3%), anemia (21.6%), and thrombocytopenia (18.9%). 15 patients (40.5%) experienced immune related adverse events (irAEs), all of which were hypothyroidism. Conclusions: In this trial, we demonstrated that an anthracycline-free neoadjuvant regimen consisting of penpulimab, carboplatin and taxanes in TNBC showed promising antitumor efficacy and manageable safety profile. The study is still ongoing. Clinical trial information: ChiCTR2300071925 .