Iparomlimab and tuvonralimab combined with paclitaxel and cisplatin as neoadjuvant therapy for cervical cancer: A phase II umbrella trial.

Abstract

TPS5629 Background: There is an urgent need to improve neoadjuvant therapy for locally advanced cervical cancer (LACC) and fertility-preserving neoadjuvant therapy for early-stage cervical cancer patients. However, there is no study evaluating the efficacy and safety of PD-1 and CTLA-4 dual blockade-based therapy for above clinical scenarios. The present study aims to assess QL1706 combined with paclitaxel and cisplatin as neoadjuvant therapy for LACC and early-stage cervical cancer patients for fertility-preservation respectively. Methods: Trial design: For Arm 1 (LACC), patients aged 18-75 years, with FIGO 2018 stages IB3, IIA2, IIB, or IIICr (lesion ≥4 cm, confirmed by MRI), histologically confirmed as cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma will be included. For Arm 2 (fertility preservation), patients aged 18-45 years old, who have a strong desire to preserve fertility, with FIGO 2018 stages IB2, IB3 (lesion ≤6 cm), IIA1, or IIA2 (lesion ≤6 cm) and histologically confirmed as cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma, will be included. All participants will be given 3 cycles of neoadjuvant treatment with QL1706 (5 mg/kg), paclitaxel (135-175 mg/m 2 ) and cisplatin (75-80 mg/m 2 ) per 21 days. Patients in Arm 1 (LACC) who achieve CR/PR will undergo radical hysterectomy plus lymphadenectomy after 3 cycles of neoadjuvant therapy whereas patients in Arm 2 (fertility preservation) who achieve CR/PR will undergo fertility-preserving surgery. For IB1/IB2 patients, conization or simple trachelectomy plus lymphadenectomy will be performed. For IIA1/IIA2 patients, radical trachelectomy plus lymphadenectomy will be performed. Patients achieve PD/SD will be given standard treatment according to the current NCCN guideline. The primary endpoints consist of objective response rate (ORR), pathological complete response (pCR) and changes in tumor-related biomarkers (ctDNA, etc). Secondary endpoints include 2-year overall survival (OS), 2-year disease-free survival (DFS) and adverse events. Other endpoints are 2-year pregnancy rate and infant survival rate for Arm 2. Sample size is 20 for Arm 1 and 15 for Arm 2. Clinical trial identification: NCT06878222. Clinical trial information: NCT06878222 .