Clinical trial NCT06926790: Neoadjuvant Nivolumab Plus Ipilimumab in Resectable NSCLC (GALAXY 3)
Official title: Neoadjuvant Nivolumab Plus Ipilimumab in Resectable Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lung Cancer - Non Small Cell
Keywords: lung cancer
nivolumab plus ipilimumab
neoadjuvant treatment
non-small cell lung cancer
Lead sponsor: The First Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2025-04-15
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with IIA-IIIB NSCLC received neoadjuvant Nivolumab (3 mg/kg intravenously (i.v.), every 3 week) plus Ipilimumab (1 mg/kg i.v., every 6 week).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathological Complete Response (PCR)
timeFrame: Within 2 weeks after surgery
Secondary outcomes:
measure: 3-year Event-Free Survival (3-year EFS）
timeFrame: From neoadjuvant treatment to the date of death, recurrence, progression, or the last follow-up (assessed up to 3 years).
measure: Major Pathological Response (MPR)
timeFrame: Within 2 weeks after surgery
measure: Safety (Rate of grade 3 and higher grade treatment-related adverse events (TRAEs))
timeFrame: Between the last dose of neoadjuvant treatment and surgery (assessed up to 30 days)
measure: Radiological Response
timeFrame: Between the last dose of neoadjuvant treatment and surgery
measure: Postoperative complications
timeFrame: After the surgery assess to 90 days
measure: Intraoperative bleeding
timeFrame: Up to approximately 20 weeks
measure: The Quality of Life
timeFrame: From the Day 1 to at least 90 days after surgery
measure: Duration of surgery
timeFrame: Up to approximately 20 weeks
measure: Hospital Stay
timeFrame: Up to approximately 20 weeks
measure: Feasibility (Completion rate of neoadjuvant treatment and surgery)
timeFrame: From date of treatment allocation until surgery, assessed up to 5 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
Study officials:
References: