Metabolic Biomarkers Predicting Response to Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer

NCT07084610 | Recruiting Phase 2 DMC

• 1 other identifier: CAAE: 80521924.0.0000.5440
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates metabolic glycolytic biomarkers obtained from radiological imaging (18F-FDG PET/CT), immunohistochemistry (IHC), and molecular analyses, and their association with response to neoadjuvant immunotherapy in early-stage non-small cell lung cancer (NSCLC). Objective: To evaluate the relationship between glycolytic biomarkers measured by PET/CT (metabolic tumor volume and SUVmax), IHC markers (GLUT-1, Ki-67, PD-L1), and molecular oncogenic alterations, with the pathological response after two cycles of neoadjuvant nivolumab (3 mg/kg) combined with platinum-based chemotherapy in patients with early-stage NSCLC \[stage IB (tumor ≥4 cm) to IIIA\], negative for EGFR and ALK mutations. Methods: This is a prospective, single-arm clinical study at a single institution, enrolling 30 patients. Baseline metabolic tumor volume (MTV) and SUVmax will be measured by PET/CT, while IHC markers and molecular profiling will be performed on pre-treatment biopsy samples. Patients will receive neoadjuvant treatment with nivolumab (3 mg/kg, IV) combined with platinum-based chemotherapy (cisplatin 75 mg/m² or carboplatin AUC 5, plus pemetrexed 500 mg/m² for non-squamous or paclitaxel 175 mg/m² for squamous tumors) every 21 days for two cycles. All patients will undergo invasive mediastinal staging before treatment and will be treated with robotic-assisted anatomical lung resection and mediastinal lymphadenectomy after neoadjuvant therapy. Primary outcomes include major pathological response (≤10% viable tumor cells) and immune profile characterization (IHC for CD8, CD4, FOXP3, PD-1, CD68, CD163). Secondary outcomes include event-free survival and treatment toxicity. Standard of Care: Neoadjuvant chemotherapy regimens and PET/CT scans are part of the institutional standard of care for NSCLC patients. Conclusion: The study aims to develop a practical diagnostic approach using metabolic glycolytic biomarkers to improve selection of patients likely to benefit from neoadjuvant immunotherapy. It is expected that patients with lower glycolytic activity will have higher rates of major pathological response after two cycles of neoadjuvant nivolumab (3 mg/kg) combined with chemotherapy. These findings may support a more cost-effective immunotherapy regimen for early-stage NSCLC.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Major pathological response (MPR) rate

  MPR will be defined as ≤10% of viable tumor cells in the resected surgical specimen, assessed by standardized pathological examination after lung resection.

  At the time of surgery, approximately 6 to 8 weeks after the beginning of neoadjuvant treatment

Study Arms (1)

Neoadjuvant Nivolumab Plus Platinum-Based Chemotherapy

EXPERIMENTAL

Patients with resectable non-small cell lung cancer (NSCLC) clinical stage IB-IIIA (AJCC 8th edition) will receive two cycles of neoadjuvant nivolumab at 3 mg/kg combined with platinum-based doublet chemotherapy. Invasive mediastinal staging will be performed prior to neoadjuvant treatment. Following completion of systemic therapy, patients will undergo minimally invasive surgery (preferably robotic-assisted anatomical resection and mediastinal lymphadenectomy).

Drug: Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant)

Interventions

Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant) DRUG

Patients will receive neoadjuvant treatment with nivolumab (3 mg/kg, IV) combined with platinum-based chemotherapy (cisplatin 75 mg/m² or carboplatin AUC 5, plus pemetrexed 500 mg/m² for non-squamous or paclitaxel 175 mg/m² for squamous tumors) every 21 days for two cycles. All patients will undergo invasive mediastinal staging before treatment and will be treated with robotic-assisted anatomical lung resection and mediastinal lymphadenectomy after neoadjuvant therapy.

Also known as: Neoadjuvant ICI + chemotherapy NSCLC

Neoadjuvant Nivolumab Plus Platinum-Based Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital das Clínicas de Ribeirão Preto: lead

Study Sites (1)

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP-USP)

Ribeirão Preto, São Paulo, 14040-906, Brazil

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Platinum Compounds; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Combined Modality Therapy; Therapeutics

Study Officials

• 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)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Saulo B Silva, Associate Professor, MD, PhD

CONTACT

+5516997602574; sbrito@fmrp.usp.br

Federico EG Cipriano, MD, PhD

CONTACT

55163602-2037; fgarciacipriano@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm, prospective, open-label study evaluating neoadjuvant nivolumab combined with chemotherapy in early-stage NSCLC.

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: July 24, 2025
• Study Start: February 25, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: August 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD and supporting documentation will be available beginning 6 months after publication of the main results and will be accessible for up to 5 years.
• Access Criteria: Qualified researchers may request access to de-identified individual participant data (IPD) and supporting documents (study protocol, SAP, ICF, CSR). Access will be granted upon reasonable request and after approval by the principal investigator and ethics committee. Requests must be made via email and include a research proposal and data use agreement.

Locations

BR (1)