Non-Small Cell Lung CancerPhase 2NCT07084610
Metabolic Biomarkers Predicting Response to Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer
A Phase 2 study testing Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant) in people with Non-Small Cell Lung Cancer, run by Hospital das Clínicas de Ribeirão Preto at 1 site in Brazil.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBrazil
- Study dates
- 25 Feb 2025to Jan 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP-USP)
Ribeirão Preto, São Paulo, 14040-906
Saulo B Silva, Associate Professor, MD, PhD, 5516997602574, sbrito@fmrp.usp.br
About this study
Official title: Metabolic Signatures Predictive of Response to Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer
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.
Read more
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.
Read the 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
- Being tested
- Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant)Drug
Also called Neoadjuvant ICI + chemotherapy NSCLC
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At the time of surgery, approximately 6 to 8 weeks after the beginning of neoadjuvant treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2025
- Study start25 Feb 2025
- Primary completionJul 2027 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm, prospective, open-label study evaluating neoadjuvant nivolumab combined with chemotherapy in early-stage NSCLC.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital das Clínicas de Ribeirão Preto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Saulo B Silva, Associate Professor, MD, PhD, Principal investigator, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP-USP)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07084610
- Sponsor's protocol ID
- CAAE: 80521924.0.0000.5440
- Other IDs
- CAAE: 80521924.0.0000.5440
- Status last verified
- Sep 2026
- First submitted
- 17 Jul 2025
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) related to study outcomes (e.g., response to treatment, survival, toxicity) will be made available to researchers upon reasonable request, following publication of the main results. Data will be shared through institutional channels and upon approval by the principal investigator and ethics committee. Data will be available for a period of 5 years after publication.
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Signatures Predictive of Response to Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT07084610
- Acronym / sponsor ID
- CAAE: 80521924.0.0000.5440
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hospital das Clínicas de Ribeirão PretoUniversity, hospital or other
- Study start
- 25 Feb 2025 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 24 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm, prospective, open-label study evaluating neoadjuvant nivolumab combined with chemotherapy in early-stage NSCLC.
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Nivolumab Plus Platinum-Based Chemotherapy | Experimental | Drug: Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant)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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant)Also: Neoadjuvant ICI + chemotherapy NSCLCPatients 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. | Drug | Neoadjuvant Nivolumab Plus Platinum-Based Chemotherapy |
Primary outcome
Major pathological response (MPR) rate
Time frame: At the time of surgery, approximately 6 to 8 weeks after the beginning of neoadjuvant treatment
MPR will be defined as ≤10% of viable tumor cells in the resected surgical specimen, assessed by standardized pathological examination after lung resection.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) related to study outcomes (e.g., response to treatment, survival, toxicity) will be made available to researchers upon reasonable request, following publication of the main results. Data will be shared through institutional channels and upon approval by the principal investigator and ethics committee. Data will be available for a period of 5 years after publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Saulo B Silva, Associate Professor, MD, PhD principal investigator
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP-USP)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant) in people with Non-Small Cell Lung Cancer, run by Hospital das Clínicas de Ribeirão Preto at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Saulo B Silva, Associate Professor, MD, PhD (+5516997602574, sbrito@fmrp.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major pathological response (MPR) rate (time frame: At the time of surgery, approximately 6 to 8 weeks after the beginning of neoadjuvant treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.