Neoadjuvant Nivolumab Plus Ipilimumab in Resectable NSCLC (GALAXY 3) (GALAXY 3)

Neoadjuvant Nivolumab Plus Ipilimumab in Resectable Non-small Cell Lung Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer - Non Small Cell
• Intervention / Treatment: Drug: Nivolumab & Ipilimumab

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 Type: Interventional
• Enrollment (Estimated): 69
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shuben Li, Professor; Phone Number: 020-8306-2114; Email: 13500030280@163.com

Study Locations

• China
  • Guangzhou, China, 510120
    • Recruiting
    • First Affiliated Hospital of Guangzhou Medical University
    • Contact: Shuben Li, PHD; Phone Number: +8613925810521; Email: 13500030280@163.com
    • Contact: Jiawei Chen, PHD; Phone Number: +8613925810521; Email: m13925810521@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant treatment; 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.	Drug: Nivolumab & Ipilimumab; This study evaluates the safety and efficacy of neoadjuvant nivolumab plus ipilimumab for IIA-IIIB NSCLC. Based on preliminary trial results, this study proposes a new treatment regimen.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Event-Free Survival (3-year EFS）	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.	From neoadjuvant treatment to the date of death, recurrence, progression, or the last follow-up (assessed up to 3 years).
Major Pathological Response (MPR)	Major pathological response defined as less than 10% of viable tumor cells in primary tumor.	Within 2 weeks after surgery
Safety (Rate of grade 3 and higher grade treatment-related adverse events (TRAEs))	Adverse events will be evaluated and recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).	Between the last dose of neoadjuvant treatment and surgery (assessed up to 30 days)
Radiological Response	Radiographic response will be evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.	Between the last dose of neoadjuvant treatment and surgery
Postoperative complications	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.	After the surgery assess to 90 days
Intraoperative bleeding	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.	Up to approximately 20 weeks
The Quality of Life	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.	From the Day 1 to at least 90 days after surgery
Duration of surgery	Duration of surgery is the time spent in surgery.	Up to approximately 20 weeks
Hospital Stay	Hospital Stay is the length of inpatient time spent in hospital.	Up to approximately 20 weeks
Feasibility (Completion rate of neoadjuvant treatment and surgery)	Propotion of patients who complete neoadjuvant treatment and receive surgery within 42 days after neoadjuvant treatment	From date of treatment allocation until surgery, assessed up to 5 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): October 31, 2030

Study Registration Dates

• First Submitted: March 30, 2025
• First Submitted That Met QC Criteria: April 11, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: lung cancer; non-small cell lung cancer; neoadjuvant treatment; nivolumab plus ipilimumab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab; Ipilimumab
• Other Study ID Numbers: ES-2025-027-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes