The preliminary efficacy and safety results of neoadjuvant phase 2 study of penpulimab combined with taxanes and carboplatin in triple-negative breast cancer (neoTAPPL).

e12617 Background: The KEYNOTE-522 trial demonstrated the addition of pembrolizumab to anthracycline-taxane-platinum chemotherapy improves pathologic complete response (pCR) and event free survival (EFS) in triple-negative breast cancer (TNBC). Penpulimab is a newly developed PD-1 monoclonal antibody with complete elimination of FcgR binding and ADCC/ADCP. This study aims to assess the efficacy of the anthracycline free neoadjuvant regimen of penpulimab plus carboplatin and taxanes in TNBC. Methods: In this open-label, phase 2 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), EFS, overall survival (OS), adverse events (AE), and immune response biomarkers. Based on the Simon’s Two-Stage design, if >7 of 16 patients achieved pCR, the enrollment would proceed to full accrual of 46 patients as planned. If >23 of 46 patients achieved pCR, we would deem the study to have met the primary endpoint. Results: Nine out of 16 pts achieved pCR in the first stage, reaching the threshold for the second stage. From Nov 2022 to Jan 2024, 22 patients were enrolled, among which 17 patients received neoadjuvant treatment and underwent breast surgery. The median age was 51 years (range, 32-69). 13 (76.5%) patients had stage II breast cancer at diagnosis. 10 of the 17 patients achieved pCR (58.8%; 95% CI, 32.9-81.6), and 12 patients achieved RCB 0-I (70.6%; 95% CI, 44.0%-89.7%). Subgroup analysis showed the pCR rate of patients who were diagnosed initially to be lymph node negative was 75.0% (6/8), higher than that of patients who were lymph node positive (44.4%; 4/9). The ORR and DCR were 82.4% (95% CI, 56.6%-96.2%) and 88.2% (95% CI, 63.6%-98.5%), respectively. Treatment-emergent adverse events (TEAEs) of any grade occurred in all 17 pts, in which 10 (58.8%) were grade ≥3. The most common grade ≥3 TEAEs were neutropenia (47.1%), leukopenia (41.2%), anemia (23.5%), and thrombocytopenia (17.6%). 6 patients (35.3%) experienced immune related adverse events (irAEs), all of which were grade 1 hypothyroidism. Conclusions: The preliminary results demonstrated that penpulimab plus carboplatin and taxanes as neoadjuvant therapy for early-stage TNBC showed promising antitumor efficacy and manageable safety profile. The study is still ongoing. Clinical trial information: ChiCTR2300071925.