Camrelizumab plus nab-paclitaxel and cisplatin as first-line treatment for metastatic triple-negative breast cancer: A prospective, single-arm, open-label phase II trial.

1101 Background: Platinum-based chemotherapy plays an important role in the treatment of TNBC. Our previous research has demonstrated the superiority of nab-paclitaxel/cisplatin (AP) regimen as the initial treatment for metastatic TNBC(mTNBC; Xichun Hu, 2020ESMO) . Camrelizumab is a humanized monoclonal antibody against PD-1. Herein, we conducted this prospective, single arm, open-label phase II study to evaluate the efficacy and safety of camrelizumab in combination with AP regimen as the first-line treatment of mTNBC (NCT04537286). Methods: Patients with untreated mTNBC received camrelizumab (200 mg D1), nab-paclitaxel (125 mg/m 2 D1,D8) and cisplatin (75 mg/m 2 D1) intravenously every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR),overall survival (OS) and safety. Exploratory analyses included immunohistochemistry and RNA sequencing of archival tumour samples. Results: A total of 90 patients were enrolled. Overall, median age was 51 years; 46.7% of patients had three or more metastatic sites; 78.9% of patients had visceral involvement; 82.2% of patients had taxanes exposure. As of data cutoff (July 10th 2024), median duration of follow-up was 18.1 months. Median PFS was 11.8 (95%CI 10.1-13.6) months and median OS was 27.1 (95%CI 22.1-33.6) months. ORR was 71.1% and DCR was 86.7%. Median time to response was 1.5 months. TRAEs were reported in all patients while grade 3-4 TRAE occurred in 55.6% patients, including neutropenia (34.4%), leukemia (24.4%), and anemia (10.0%). irAEs were reported in 57.8% patients, including RCCEP (45.5%), rash (11.1%), pneumonitis (10.0%), while grade 3-4 irAEs only occurred in 4.4% patients. Three-months landmark analyses showed that patients with irAE have significantly longer OS than those without (29.3 vs. 22.1 months, P = 0.018). Exploratory analyses demonstrated that patients with PDL1 CPS ≥10 had significantly longer PFS (13.7 vs 11.4 months, P = 0.039). Patients with high TILs had significantly longer OS (23.1 vs.10.3 months, P = 0.003). The proportion of PDL1 positive (CPS ≥1) patients was 81.8% in basal compared to 0% in non-basal subtype ( P = 0.023). Hallmark pathway analysis showed that the activation of DNA repair pathway (HR,11.6, 95%CI 2.4-55.7, P = 0.002) and MYC target pathway (HR,7.4,95%CI 1.9-28.2, P = 0.004) was significantly associated with shorter PFS, while the activation of KRAS signaling (HR,3.2, 95%CI 1.1-9.7, P = 0.035) was significantly associated with worse OS. Conclusions: Camrelizumab plus AP as first-line treatment in patients with mTNBC demonstrated satisfying efficacy with manageable toxicity. Randomized controlled trial is warranted in the future. Clinical trial information: NCT04537286 .