Metabolic biomarkers to predict response to pre-surgery immunotherapy in early non-small cell lung cancer.

Metabolic Signatures Predictive of Response to Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer

This will test whether PET/CT metabolic measures and tumor biopsy markers can predict how people with early-stage, EGFR/ALK-negative non-small cell lung cancer respond to two cycles of nivolumab plus platinum chemotherapy before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hospital das Clínicas de Ribeirão Preto (Academic / other)
• Drugs / interventions: immunotherapy, nivolumab, chemotherapy
• Locations: 1 site (Ribeirão Preto, São Paulo)
• Trial ID: NCT07084610 on ClinicalTrials.gov

What this trial studies

This prospective, single-arm, single-center Phase 2 study will enroll 30 patients with resectable stage IB (≥4 cm) to IIIA NSCLC who are negative for EGFR and ALK alterations. Participants receive two cycles of neoadjuvant nivolumab (3 mg/kg) combined with platinum-doublet chemotherapy followed by surgical resection. Baseline 18F-FDG PET/CT will measure metabolic tumor volume (MTV) and SUVmax, and pre-treatment biopsies will undergo immunohistochemistry for GLUT-1, Ki-67, PD-L1 and molecular profiling for oncogenic alterations. Primary endpoints are major pathological response (≤10% viable tumor) and immune microenvironment characterization, with secondary endpoints including event-free survival, overall survival, and treatment-related toxicity.

Who should consider this trial

Good fit: Ideal candidates are adults with resectable stage IB (tumor ≥4 cm) to IIIA NSCLC, ECOG performance status 0–1, negative for EGFR and ALK, and able to undergo PET/CT, biopsy, neoadjuvant therapy, and surgery.

Not a fit: Patients with known EGFR or ALK alterations, unresectable disease, poor performance status, contraindications to immunotherapy or surgery, or recent other malignancies are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, these biomarkers could help identify which patients are most likely to benefit from pre-surgery immunotherapy plus chemotherapy, enabling more personalized treatment decisions.

How similar studies have performed: Some retrospective and small prospective studies have linked PET metabolic measures and IHC markers to immunotherapy outcomes, but prospective validation in the neoadjuvant setting is limited and this specific multimodal biomarker approach remains relatively untested.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed non-small cell lung cancer (NSCLC), clinical stage IB to IIIA (according to AJCC 8th edition)
* Tumor deemed resectable by the multidisciplinary thoracic oncology team
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Adequate organ and bone marrow function
* Ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

* Prior systemic therapy, radiotherapy, or immunotherapy for lung cancer
* Known EGFR mutations or ALK rearrangements
* Active autoimmune disease requiring systemic therapy within the past 2 years
* Uncontrolled comorbidities or active infections
* Pregnant or breastfeeding women
* Contraindications to surgery or anesthesia
* Known history of other malignancies within the last 3 years, except for adequately treated basal or squamous cell skin cancer, or carcinoma in situ of the cervix

Where this trial is running

Ribeirão Preto, São Paulo

• Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP-USP) — Ribeirão Preto, São Paulo, Brazil (Recruiting)

Study contacts

• Principal investigator: Saulo B Silva, Associate Professor, MD, PhD — Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP-USP)
• Study coordinator: Saulo B Silva, Associate Professor, MD, PhD

Conditions Non-Small Cell Lung Cancer