Neoadjuvant Nivolumab Plus Ipilimumab in Resectable NSCLC (GALAXY 3)

Phase 2

Recruiting

• Conditions: Lung Cancer - Non Small Cell
• Interventions: Drug: Nivolumab & Ipilimumab

• Registration Number: NCT06926790
• Lead Sponsor: The First Affiliated Hospital of Guangzhou Medical University

Brief Summary

Neoadjuvant immunotherapy followed by surgery has emerged as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). However, conventional chemotherapy components may increase treatment-related toxicity, particularly in elderly populations. Additionally, the efficacy of preoperative immunochemotherapy for patients with PD-L1 expression \<1% remains to be improved. Emerging evidence has demonstrated that the combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) provides superior responses in the treatment of advanced NSCLC. However, the safety and efficacy of this strategy in the neoadjuvant setting remain controversial. Therefore, this single-arm clinical trial aims to evaluate the safety and feasibility of neoadjuvant nivolumab plus ipilimumab followed by surgery in treating locally advanced and resectable NSCLC.

Detailed Description

Lung cancer remains the leading cause of cancer-related death globally. Neoadjuvant immunotherapy followed by surgery has been emerged as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). Numerous clinical trials highlighted the efficacy of preoperative immunochemotherapy, including remarkably shrinking the primary lesion, eliminating micrometastases and ultimately contributing to survival outcomes. Notably, studies also demonstrated neoadjuvant immunochemotherapy increased the access of modified surgery and enhanced survival prognosis of patients with locally advanced NSCLC (IIIB).

Despite these advances, certain limitations remain. Conventional chemotherapy components may elevate treatment-related toxicity, particularly in elderly populations. Additionally, the efficacy of preoperative immunochemotherapy for patients with PD-L1\<1% remained to be improve. Emerging evidences demonstrated that nivolumab (anti-PD-1) combine with ipilimumab (antiCTLA-4) provided superior response for the treatment of advanced NSCLC patients. However, the safety and efficacy of this strategy in the neoadjuvant setting remain controversial. Therefore, this single-arm clinical trial aims to evaluate the safety and feasibility of neoadjuvant nivolumab plus ipilimumab followed by surgery in treating locally advanced and resectable NSCLC. The study will enroll 69 eligible participants, with the primary endpoint being pathological complete response (pCR) rate following neoadjuvant therapy.

Study Timeline

• Study Start: 2025-02-17
• Status Verified: 2025-03
• Study First Submitted: 2025-03-30
• Study First Submitted QC: 2025-04-11
• Study First Posted: 2025-04-15
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-22
• Primary Completion: 2030-03-31
• Study Completion: 2030-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

1. Informed consent must be signed.
2. At least 18 years of age.
3. Histologically or cytologically confirmed non-small cell lung cancer (without EGFR, ALK mutation).
4. Have measurable and clinical stage II-IIIA with no known PD-L1 expression or PD-L1 ≤ 1%.
5. disease eligible for surgery.
6. No previous systematic therapy or radiotherapy.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. At least one measurable lesion.
9. No major organ dysfunction, including liver, kidney, and cardiac function.

Exclusion Criteria

1. Patients with active autoimmune disease or history of autoimmune disease.
2. Patients have received other treatment for non-small cell lung cancer or for any other malignancy.
3. History of allergy to study drug components.
4. Pregnant or breast-feeding.
5. Any mental or psychological condition that would prevent the patient from completing the study or understanding the patient information.
6. Patients who have other malignancies.
7. History of major surgery or serious injury within the past 3 months.
8. HIV, HBV, HCV infection or active pulmonary tuberculosis.
9. Vaccination within 4 weeks prior to the start of the study.
10. Presence of underlying medical conditions that, in the investigator's judgment, could increase the risk associated with study drug administration or interfere with the assessment of toxicity and adverse events.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant treatment	Nivolumab & Ipilimumab	Patients with IIA-IIIB NSCLC will received 2-3 cycles of neoadjuvant Nivolumab (3 mg/kg intravenously (i.v.), every 3 week) plus Ipilimumab (1 mg/kg i.v., every 6 week). Surgery will be performed within 4 to 6 weeks after completion of preoperative therapy. After the second cycles treatment, contrast-enhanced chest CT will be performed to evaluate the tumor.

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response (PCR)	Within 2 weeks after surgery	Pathological complete response is predefined as no residual viable tumor cells in primary tumor and lymph nodes.

Secondary Outcome Measures

Name	Time	Method
3-year Event-Free Survival (3-year EFS）	From neoadjuvant treatment to the date of death, recurrence, progression, or the last follow-up (assessed up to 3 years).	The starting point for EFS was the initiation of neoadjuvant treatment. The endpoint for EFS was defined as the date of death, recurrence, progression, or the last follow-up.
Major Pathological Response (MPR)	Within 2 weeks after surgery	Major pathological response defined as less than 10% of viable tumor cells in primary tumor.
Safety (Rate of grade 3 and higher grade treatment-related adverse events (TRAEs))	Between the last dose of neoadjuvant treatment and surgery (assessed up to 30 days)	Adverse events will be evaluated and recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).
Radiological Response	Between the last dose of neoadjuvant treatment and surgery	Radiographic response will be evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Postoperative complications	After the surgery assess to 90 days	Postoperative complications will be evaluated and recorded after the surgery following Clavien-Dindo grade. The minimum and maximum values were grade I-V, and the higher scores mean a worse outcomes.
Intraoperative bleeding	Up to approximately 20 weeks	Intraoperative bleeding was assessed and recorded by the surgical team. Blood loss was estimated by measuring suction canister volume and weighing surgical sponges, subtracting irrigation fluid.
The Quality of Life	From the Day 1 to at least 90 days after surgery	The quality of life will be evaluated and recorded according to the EORTC QLQ-C30. The minimum and maximum values were 0-100, and the higher scores mean a better outcome.
Duration of surgery	Up to approximately 20 weeks	Duration of surgery is the time spent in surgery.
Hospital Stay	Up to approximately 20 weeks	Hospital Stay is the length of inpatient time spent in hospital.
Feasibility (Completion rate of neoadjuvant treatment and surgery)	From date of treatment allocation until surgery, assessed up to 5 months	Propotion of patients who complete neoadjuvant treatment and receive surgery within 42 days after neoadjuvant treatment

Trial Locations

Locations (1)

First Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, China