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Iparomlimab and Tuvonralimab Plus Chemotherapy Before Surgery for Stage III Lung Cancer
Sponsor: Tang-Du Hospital
Summary
Background: For patients with resectable stage III-N2b non-small cell lung cancer (NSCLC), optimal perioperative treatment strategies remain an area of active investigation. Iparomlimab and tuvonralimab (QL1706) is a novel bifunctional antibody combination targeting PD-1 and CTLA-4, designed to enhance anti-tumor immunity. Objective: This phase II, single-arm, multicenter study aims to evaluate the efficacy and safety of neoadjuvant iparomlimab and tuvonralimab (QL1706) in combination with platinum-based chemotherapy in patients with resectable stage III-N2b NSCLC. Study Design and Methods: A total of 28 patients will be enrolled across approximately 4 centers in China. Eligible patients (aged ≥18 years, ECOG PS 0-1) with histologically or cytologically confirmed, resectable stage III-N2b NSCLC (AJCC 9th edition) will receive three cycles of neoadjuvant therapy every three weeks. Patients with non-squamous carcinoma will receive iparomlimab and tuvonralimab (5 mg/kg) plus pemetrexed (500 mg/m²) and carboplatin (AUC 5). Patients with squamous carcinoma will receive iparomlimab and tuvonralimab (5 mg/kg) plus nab-paclitaxel (260 mg/m²) and carboplatin (AUC 5). Surgical resection will be performed within 6 weeks following completion of neoadjuvant therapy. Subsequent adjuvant treatment is at the discretion of the investigator. Key Eligibility Criteria: Key inclusion criteria include pathologically confirmed T\<sub\>any\</sub\>N2b disease with mediastinal nodal status confirmed by EBUS/EUS or mediastinoscopy, and the determination by multidisciplinary team (MDT) assessment that the tumor is completely resectable (R0). Key exclusion criteria include known EGFR or ALK positive mutations, prior anti-cancer therapy for current lung cancer, active autoimmune disease, or uncontrolled hepatitis B or C. Study Endpoints: The primary endpoint is the pathological complete response (pCR) rate. Secondary endpoints include major pathological response (MPR) rate, objective response rate (ORR), R0 resection rate, event-free survival (EFS), overall survival (OS), impact on surgical outcomes, and safety. Exploratory endpoints involve biomarker analysis including ctDNA. Sample Size Rationale: Assuming a null hypothesis pCR rate (P0) of 8.8% (based on historical data) and an expected pCR rate (P1) of 28%, with a two-sided α of 5% and 80% power, 24 patients are required. Factoring in a 15% inoperable rate, the total sample size is 28 patients. Statistical Analysis: The primary endpoint, pCR rate, and other binary endpoints will be summarized with frequencies, percentages, and their 95% confidence intervals calculated using the Clopper-Pearson method. Time-to-event endpoints (EFS, OS) will be analyzed using the Kaplan-Meier method. Safety data will be summarized descriptively. Clinical Trial Information: This study is sponsored by The Second Affiliated Hospital of Air Force Medical University, PLA. The Principal Investigator is Dr. Yan Xiaolong.
Official title: A Study of Iparomlimab and Tuvonralimab in Combination With Chemotherapy as Neoadjuvant Therapy for Resectable Stage III-N2b Non-Small Cell Lung Cancer
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
28
Start Date
2026-05
Completion Date
2029-12
Last Updated
2026-04-20
Healthy Volunteers
No
Interventions
Iparomlimab and Tuvonralimab combined with Platinum-Based Chemotherapy (Pemetrexed/Carboplatin for Non-squamous; Nab-paclitaxel/Carboplatin for Squamous)
Participants receive neoadjuvant treatment with Iparomlimab and Tuvonralimab in combination with platinum-based chemotherapy for three cycles prior to surgical resection. Dosing Regimen: For Non-squamous Carcinoma: Iparomlimab and Tuvonralimab: 5 mg/kg, intravenous infusion, Day 1 Pemetrexed: 500 mg/m², intravenous infusion, Day 1 Carboplatin: AUC 5, intravenous infusion, Day 1 Cycle length: 21 days (every 3 weeks) Total treatment: 3 cycles For Squamous Carcinoma: Iparomlimab and Tuvonralimab: 5 mg/kg, intravenous infusion, Day 1 Nab-paclitaxel: 260 mg/m², intravenous infusion, Day 1 Carboplatin: AUC 5, intravenous infusion, Day 1 Cycle length: 21 days (every 3 weeks) Total treatment: 3 cycles After completion of neoadjuvant therapy, participants undergo surgical resection within 6 weeks. Adjuvant treatment following surgery is administered at the discretion of the investigator and is not specified by this protocol.
Locations (1)
Tangdu Hospitial
Xi'an, Shannxi, China