Neoadjuvant therapy of iparomlimab and tuvonralimab combined with chemotherapy-extenuated for locally advanced cervical cancer (NICE-CC): an investigator-initiated, multicentre, open-label, phase II trial.

BACKGROUND

Neoadjuvant treatments combining anti-programmed cell death 1 (PD-1) inhibitors with chemotherapy induce higher pathologic response rates than chemotherapy alone in patients with locally advanced cervical cancer (LACC). A dual blocker that targets PD-1 and cytotoxic T lymphocyte-associated protein-4, paired with de-escalated chemotherapy, may improve treatment efficacy while reducing toxicity. This study aims to evaluate the efficacy and safety of neoadjuvant iparomlimab and tuvonralimab in conjunction with reduced courses of chemotherapy for LACC.

METHODS

In this multi-center, single-arm, open-label, phase II trial, patients with histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma are eligible. A total of 43 patients diagnosed with International Federation of Gynecology and Obstetrics 2018 stage IB3, IIA2, IIB, or IIIC1r will receive iparomlimab and tuvonralimab (5 mg/kg, intravenously), nab-paclitaxel (60 mg/m², intravenously), and cisplatin (75-80 mg/m², intravenously) for the first cycle. Then, 2 additional cycles of iparomlimab and tuvonralimab (5 mg/kg, intravenously) were followed at 3-week intervals. After finishing 3 cycles of neoadjuvant treatment, patients who exhibit a complete response (CR) or partial response (PR) will proceed to radical surgery, and subsequent adjuvant therapy will be guided by the National Comprehensive Cancer Network guidelines. Conversely, patients with stable or progressive disease will transition to concurrent chemoradiotherapy. The primary endpoint is the pathological CR. Secondary endpoints include the objective response rate, event-free survival, major PR, disease-free survival rate, and safety. Additionally, the exploratory endpoint will focus on identifying predictive biomarkers associated with tumor response.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07055399.