Neoadjuvant Nivolumab Plus Ipilimumab in Resectable NSCLC (GALAXY 3)

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Pathological Complete Response (PCR) [Time frame: Within 2 weeks after surgery]

Secondary outcome measures (10)

• 3-year Event-Free Survival (3-year EFS） [Time frame: From neoadjuvant treatment to the date of death, recurrence, progression, or the last follow-up (assessed up to 3 years).]
• Major Pathological Response (MPR) [Time frame: Within 2 weeks after surgery]
• Safety (Rate of grade 3 and higher grade treatment-related adverse events (TRAEs)) [Time frame: Between the last dose of neoadjuvant treatment and surgery (assessed up to 30 days)]
• Radiological Response [Time frame: Between the last dose of neoadjuvant treatment and surgery]
• Postoperative complications [Time frame: After the surgery assess to 90 days]
• Intraoperative bleeding [Time frame: Up to approximately 20 weeks]
• The Quality of Life [Time frame: From the Day 1 to at least 90 days after surgery]
• Duration of surgery [Time frame: Up to approximately 20 weeks]
• Hospital Stay [Time frame: Up to approximately 20 weeks]
• Feasibility (Completion rate of neoadjuvant treatment and surgery) [Time frame: From date of treatment allocation until surgery, assessed up to 5 months]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Patients with active autoimmune disease or history of autoimmune disease.
• Patients have received other treatment for non-small cell lung cancer or for any other malignancy.
• History of allergy to study drug components.
• Pregnant or breast-feeding.
• Any mental or psychological condition that would prevent the patient from completing the study or understanding the patient information.
• Patients who have other malignancies.
• History of major surgery or serious injury within the past 3 months.
• HIV, HBV, HCV infection or active pulmonary tuberculosis.
• Vaccination within 4 weeks prior to the start of the study.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• First Affiliated Hospital of Guangzhou Medical University — Guangzhou

Identifiers

NCT: NCT06926790 · ES-2025-027-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗