Stage III NSCLCPhase 2NCT07264647
Neoadjuvant Chemo-immunotherapy for Stage III PD-L1 Positive Non-Small Cell Lung Cancer (NSCLC)
A Phase 2 study testing Tislelizumab, surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines and Chemoradiotherapy in people with Stage III NSCLC, run by Fondazione Ricerca Traslazionale at 1 site in Italy.
Trial summary
A Ph.2, single-arm, monocentric, trial of neo-adjiuvant chemo-immunotherapy for stage III, PD-L1 positive, NSCLC. Adults and smokers (past or current) diagnosed with stage III NSCLC without driver molecular alterations (EGFR, ALK, ROS1, RET). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Stage III NSCLC
- What is being tested?
- Tislelizumab, surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines and Chemoradiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 27 Mar 2025to 1 Feb 2030
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed stage III disease.
- PD-L1 TPS ≥ 1% according to local testing.
- No evidence of EGFR mutations or ALK or ROS1 or RET rearrangements by local testing.
- Mandatory baseline multidisciplinary assessment to confirm suitability of patient to local treatment with curative intent.
- Pulmonary function tests within 6 months of the planned resection.
- At least 1 measurable lesion as defined by RECIST v1.1.
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- ECOG Performance Status ≤ 1.
- Eligibility to receive a platinum doublet chemotherapy regimen.
- Adequate organ function as indicated by the following laboratory values obtained ≤ 14 days before the first dose of study drug:
- Patients must not have required blood transfusion or growth factor support ≤ 14 days before sample collection at screening for the following:
- Absolute neutrophil count ≥ 1.5 x 109 /L Platelets ≥ 75 x 109 /L Hemoglobin ≥ 90 g/L Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation (Appendix 9).
- For patients intended to receive cisplatin: creatinine clearance 60mL/min For patients intended to receive carboplatin: creatinine clearance 45mL/min Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome).
- AST and ALT ≤ 2.5 x ULN For patients not receiving therapeutic anticoagulation: international normalized ratio or activated partial thromboplastin time 1.5ULN
- Age ≥ 18 years.
- Written informed consent.
Who cannot join
- Evidence of stage IV NSCLC (metastatic disease).
- Histology of large cell neuroendocrine carcinoma (LCNEC).
- Any previous therapy for current lung cancer, including chemotherapy or radiation therapy.
- Previous treatment with an antibody or drug against the immune checkpoint pathway, including but not limited to, therapeutic anti-cytotoxic T-lymphocyte antigen-4-associated antibodies (anti-CTLA-4), anti-PD-1 and anti-PD-L1.
- Never smoking patients.
- Active autoimmune diseases or history of autoimmune diseases that may recur.
- Concomitant participation in another therapeutic clinical trial.
- Pregnancy or breastfeeding.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Istituti Fisioterapici Ospitalieri
Rome, Roma (RM), 00144
Federico Cappuzzo, Medical Oncology, +390652665789, federico.cappuzzo@fondazionefort.org
About this study
A Ph.2, single-arm, monocentric, trial of neo-adjiuvant chemo-immunotherapy for stage III, PD-L1 positive, NSCLC.
Adults and smokers (past or current) diagnosed with stage III NSCLC without driver molecular alterations (EGFR, ALK, ROS1, RET).
Read the detailed description
Study Population: Adult smoker (past or current) patients diagnosed with stage III (NON T4 for a nodule in a different lobe) NSCLC without driver molecular alterations (EGFR, ALK, ROS1).
Treatment: Patients will receive neoadjuvant chemo-immunotherapy based on NSCLC histology.
Diagnostic Assessments: All patients will undergo a comprehensive disease staging, including contrast-enhanced chest CT, PET-CT, and contrast-enhanced brain magnetic resonance imaging. A pathological assessment of the mediastinum and lymph-node stations clinically positive/suspected is mandatory.
Treatment Cycles: Eligible patients will receive 3 cycles of neoadjuvant chemo- immunotherapy, followed by a comprehensive diagnostic assessment using chest CT and PET-CT and pathologic lymph-node reassessment.
Intervention: Patients with pathologic negativization of lymph nodes after neoadjuvant therapy will be candidate for surgery. Patients with pathologic persistence of N2 or N3 disease will be candidate for definitive concurrent chemoradiation as part of routine clinical practice. After local therapy, patients will receive 1 year of adjuvant or maintenance tislelizumab.
- Conditions
- Stage III NSCLC
- Being tested
- Tislelizumab, surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines, Chemoradiotherapy
- 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.
TislelizumabDrug
Compared to clinical practice in Italy this trial is adding a neoadjuvant chemoimmuno treatment with adjuvant immuno
surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelinesProcedure or surgery
surgery if resectable after neoadjuvant treatment
ChemoradiotherapyRadiation
if patient not resectable after neoadjuvant treatment, chemoradiotherapy performed
| Study group | Role | What they receive |
|---|---|---|
| surgery | Experimental | After a neoadjuvant chemoimmuno treatment patient is selected to the surgery and immuno maintenance arm if resectable Receives: Drug: Tislelizumab; Procedure: surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines |
| chemoradio | Active comparator | After neoadjuvant chemoimmuno treatment patient is selected to surgery and immuno maintenance arm if resectable Receives: Drug: Tislelizumab; Radiation: Chemoradiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
radical surgery (R0) in patients with stage III PD-L1 positive
To evaluate the rate of radical surgery (R0) in patients with stage III PD-L1 positive NSCLC treated with tislelizumab plus platinum-based doublet chemotherapy as neoadjuvant treatment.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2025
- Study start27 Mar 2025
- Primary completion1 Feb 2028 (estimated)
- Study completion1 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage III NSCLCStudies 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
- Non-randomised
- Intervention model
- Single group
- Model description
- This is a phase 2 clinical study, monocentric and prospective.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Ricerca Traslazionale
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Federico Cappuzzo, Principal investigator, Istituti Fisioterapici Ospitalieri
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07264647
- Sponsor's protocol ID
- CHALLENGE
- Status last verified
- Nov 2025
- First submitted
- 24 Nov 2025
- Last updated
- 4 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Chemo-immunotherapy for Stage III PD-L1 Positive Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT07264647
- Acronym / sponsor ID
- CHALLENGE
- Conditions
- Stage III NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Fondazione Ricerca TraslazionaleUniversity, hospital or other
- Study start
- 27 Mar 2025 (actual)
- Primary completion
- 1 Feb 2028 (estimated)
- Study completion
- 1 Feb 2030 (estimated)
- First posted
- 4 Dec 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.
A Ph.2, single-arm, monocentric, trial of neo-adjiuvant chemo-immunotherapy for stage III, PD-L1 positive, NSCLC.
Adults and smokers (past or current) diagnosed with stage III NSCLC without driver molecular alterations (EGFR, ALK, ROS1, RET).
Detailed description
Study Population: Adult smoker (past or current) patients diagnosed with stage III (NON T4 for a nodule in a different lobe) NSCLC without driver molecular alterations (EGFR, ALK, ROS1).
Treatment: Patients will receive neoadjuvant chemo-immunotherapy based on NSCLC histology.
Diagnostic Assessments: All patients will undergo a comprehensive disease staging, including contrast-enhanced chest CT, PET-CT, and contrast-enhanced brain magnetic resonance imaging. A pathological assessment of the mediastinum and lymph-node stations clinically positive/suspected is mandatory.
Treatment Cycles: Eligible patients will receive 3 cycles of neoadjuvant chemo- immunotherapy, followed by a comprehensive diagnostic assessment using chest CT and PET-CT and pathologic lymph-node reassessment.
Intervention: Patients with pathologic negativization of lymph nodes after neoadjuvant therapy will be candidate for surgery. Patients with pathologic persistence of N2 or N3 disease will be candidate for definitive concurrent chemoradiation as part of routine clinical practice. After local therapy, patients will receive 1 year of adjuvant or maintenance tislelizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a phase 2 clinical study, monocentric and prospective.
| Arm | Type | Receives |
|---|---|---|
| surgery | Experimental | Drug: Tislelizumab, Procedure: surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelinesAfter a neoadjuvant chemoimmuno treatment patient is selected to the surgery and immuno maintenance arm if resectable |
| chemoradio | Active comparator | Drug: Tislelizumab, Radiation: ChemoradiotherapyAfter neoadjuvant chemoimmuno treatment patient is selected to surgery and immuno maintenance arm if resectable |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed stage III disease.
- Mandatory baseline multidisciplinary assessment to confirm suitability of patient to local treatment with curative intent.
- Pulmonary function tests within 6 months of the planned resection.
- At least 1 measurable lesion as defined by RECIST v1.1.
- ECOG Performance Status ≤ 1.
Key exclusion criteria (8 listed)
- Evidence of stage IV NSCLC (metastatic disease).
- Histology of large cell neuroendocrine carcinoma (LCNEC).
- Any previous therapy for current lung cancer, including chemotherapy or radiation therapy.
- Previous treatment with an antibody or drug against the immune checkpoint pathway, including but not limited to, therapeutic anti-cytotoxic T-lymphocyte antigen-4-associated antibodies (anti-CTLA-4), anti-PD-1 and anti-PD-L1.
- Never smoking patients.
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 |
|---|---|---|
| TislelizumabCompared to clinical practice in Italy this trial is adding a neoadjuvant chemoimmuno treatment with adjuvant immuno | Drug | chemoradio, surgery |
| surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelinessurgery if resectable after neoadjuvant treatment | Procedure or surgery | surgery |
| Chemoradiotherapyif patient not resectable after neoadjuvant treatment, chemoradiotherapy performed | Radiation | chemoradio |
Primary outcome
radical surgery (R0) in patients with stage III PD-L1 positive
Time frame: 3 years
To evaluate the rate of radical surgery (R0) in patients with stage III PD-L1 positive NSCLC treated with tislelizumab plus platinum-based doublet chemotherapy as neoadjuvant treatment.
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 4 Dec 2025.
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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.
Federico Cappuzzo principal investigator
Istituti Fisioterapici Ospitalieri
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 Tislelizumab, surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines and Chemoradiotherapy in people with Stage III NSCLC, run by Fondazione Ricerca Traslazionale at 1 site in Italy.
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 15 inclusion and 8 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 4 Dec 2025. 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 Italy. 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 Federico Cappuzzo, Medical Oncology (+390652665789, federico.cappuzzo@fondazionefort.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
radical surgery (R0) in patients with stage III PD-L1 positive (time frame: 3 years). 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 4 Dec 2025.