NCT07271602

A Phase 2 Randomized, Controlled Trial of QL1706 Plus Chemotherapy and Quad Shot for Driver Gene-negative Advanced Non-small Cell Lung Cancer.

Iparomlimab and Tuvonralimab (QL1706) Combined Chemotherapy and Quad Shot Radiotherapy in First-line Treatment of Driver Gene-negative Advanced Non-small Cell Lung Cancer: a Randomized, Controlled, Phase 2, Open-label Trial.

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 104 (estimated)
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Chemotherapy combined with immunotherapy has become the first-line standard treatment regimen for metastatic non-small cell lung cancer (NSCLC). QL1706 is an antibody that can simultaneously block the CTLA-4 and PD-1. In a phase II clinical study, when QL1706 was combined with chemotherapy for first-line treatment of metastatic NSCLC, the median progression-free survival (mPFS) was 6.8 months and the objective response rate (ORR) was 45% at a median follow-up time of 12.6 months (range, 0.4-15.2 months). Radiotherapy is one of the commonly used local treatment modalities for tumors, which has a synergistic effect with immunotherapy, can enhance the response to immunotherapy, and trigger the abscopal effect. Quad shot radiotherapy is a periodic pulsed hypofractionated radiotherapy, with a specific mode as follows: 2 fractions per day, with an interval of more than 6 hours between the two fractions, for 2 consecutive days, with a total dose of 14-14.8 Gy. This regimen can be repeated every 3-4 weeks for a total of 3 cycles, with a total treatment dose of approximately 44-48 Gy, and it can be used for palliative treatment of various advanced tumors. This project intends to explore whether the addition of Quad shot radiotherapy to QL1706 combined with chemotherapy can improve local and systemic tumor control rates, prolong patients' PFS, and evaluate the safety of the combined therapy in treatment-naive patients with metastatic NSCLC.

Conditions

• Non Small Cell Lung Cancer
• Immunotherapy
• Radiotherapy
• Chemotherapy

Interventions

Type	Name	Description
RADIATION	Quad shot	Intensity-modulated radiotherapy (IMRT) technique is adopted, and only partial lesions (as determined by the investigator) receive Quad shot radiotherapy. Only the gross tumor volume (GTV) is irradiated, with no prophylactic irradiation of lymph nodes. The irradiation dose for the planning gross tumor volume (PGTV) is 14.8 Gy in 4 fractions, administered twice daily (bid), with an interval of more than 6 hours between each irradiation. The treatment is repeated every 3 weeks for a total of 3 cycles.
DRUG	Chemotherapy	For patients with lung squamous cell carcinoma, TC regimen chemotherapy combined with QL1706 is administered on days 1, 22, 43, and 64, respectively. The specific TC chemotherapy regimen is as follows: nab-paclitaxel 260 mg/m², intravenous infusion; carboplatin at an AUC of 5, with the total dose (mg) calculated as AUC × (GFR + 25), where GFR refers to glomerular filtration rate, administered via intravenous infusion. For patients with lung adenocarcinoma, PC regimen chemotherapy combined with QL1706 is administered on days 1, 22, 43, and 64, respectively. The specific PC chemotherapy regimen is as follows: pemetrexed 500 mg/m², intravenous infusion; carboplatin at an AUC of 5, with the total dose (mg) calculated as AUC × (GFR + 25), where GFR refers to glomerular filtration rate, administered via intravenous infusion.
DRUG	Immune Checkpoint Inhibitors	The specific treatment regimen for QL1706 is as follows: QL1706 (5 mg/kg) via intravenous infusion.

Timeline

• Start date: 2026-01-30
• Primary completion: 2026-12-31
• Completion: 2028-12-31
• First posted: 2025-12-09
• Last updated: 2025-12-09