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

NCT ID: NCT07084610

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-25
• Study Completion Date: 2029-01-31

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.

Detailed Description

Introduction:

Metabolic reprogramming in cancer cells is an important feature that may impact response to immunotherapy. This study focuses on assessing glycolytic biomarkers through radiological (18F-FDG PET/CT), immunohistochemical (GLUT-1, Ki-67, PD-L1), and molecular analyses to better predict treatment outcomes in early-stage non-small cell lung cancer (NSCLC).

Study Design:

This is a prospective, single-arm, single-center clinical trial including 30 patients diagnosed with early-stage NSCLC (stages IB to IIIA) who are negative for EGFR and ALK mutations. All patients will receive two cycles of neoadjuvant nivolumab at 3 mg/kg combined with platinum-based chemotherapy (doublet regimen).

Procedures:

Before treatment, patients will undergo PET/CT scans to measure metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax). Tumor biopsies will be collected for immunohistochemistry and molecular profiling to evaluate markers such as GLUT-1, Ki-67, PD-L1, and oncogenic signaling pathways related to metabolism.

Endpoints:

Primary endpoints are major pathological response defined as ≤10% viable tumor cells in surgical specimens post-treatment, and immune microenvironment characterization through IHC markers (CD8, CD4, FOXP3, PD-1, CD68, CD163). Secondary endpoints include event-free survival, overall survival, and assessment of treatment-related toxicities.

Standard of Care:

Neoadjuvant chemotherapy and PET/CT imaging are part of routine clinical management for NSCLC at the institution.

Significance:

The study aims to provide a clinically feasible diagnostic tool to optimize patient selection for neoadjuvant immunotherapy, potentially enhancing efficacy and cost-effectiveness of treatment protocols in early-stage NSCLC.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant Nivolumab Plus Platinum-Based Chemotherapy

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).

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Interventions

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

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.

Intervention Type: DRUG

Other Intervention Names

Neoadjuvant ICI + chemotherapy NSCLC

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital das Clínicas de Ribeirão Preto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Saulo B Silva, Associate Professor, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Ribeirão Preto, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Saulo B Silva, Associate Professor, MD, PhD

Role: CONTACT

sbrito@fmrp.usp.br

+5516997602574

Federico EG Cipriano, MD, PhD

Role: CONTACT

fgarciacipriano@gmail.com

55163602-2037

Facility Contacts

Saulo B Silva, Associate Professor, MD, PhD

Role: primary

sbrito@fmrp.usp.br

5516997602574

Other Identifiers

CAAE: 80521924.0.0000.5440

Identifier Type: OTHER

Identifier Source: secondary_id

CAAE: 80521924.0.0000.5440

Identifier Type: -

Identifier Source: org_study_id