Neoadjuvant chemo-immunotherapy for PD-L1–positive Stage III non-small cell lung cancer

Neoadjuvant Chemo-immunotherapy for Stage III PD-L1 Positive Non-Small Cell Lung Cancer (NSCLC)

This tests whether three cycles of combined chemotherapy and the immunotherapy drug tislelizumab given before local treatment help adults with Stage III PD-L1–positive non-small cell lung cancer who are past or current smokers and do not have EGFR/ALK/ROS1/RET driver alterations.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Fondazione Ricerca Traslazionale (Academic / other)
• Drugs / interventions: chemotherapy, radiation, immunotherapy, tislelizumab
• Locations: 1 site (Rome, Roma (RM))
• Trial ID: NCT07264647 on ClinicalTrials.gov

What this trial studies

This is a single-arm, phase 2, monocentric trial giving three cycles of neoadjuvant chemo-immunotherapy tailored by tumor histology, followed by restaging with chest CT and PET-CT and pathologic lymph-node reassessment. Patients with nodal clearance after neoadjuvant therapy will be considered for surgery, while those with persistent N2/N3 disease will proceed to definitive concurrent chemoradiation per routine practice. After local therapy, all patients will receive one year of adjuvant or maintenance tislelizumab. Enrollment is limited to adults with PD-L1 TPS ≥1% and no actionable driver mutations, and baseline multidisciplinary staging including PET-CT and brain MRI is mandatory.

Who should consider this trial

Good fit: Adults with histologically confirmed Stage III NSCLC (non-T4 for a separate-lobe nodule), PD-L1 TPS ≥1%, no EGFR/ALK/ROS1/RET alterations, ECOG 0–1, measurable disease, adequate organ function, and eligible for a platinum-doublet chemotherapy regimen are ideal candidates.

Not a fit: Patients with targetable driver mutations, PD-L1 <1%, poor performance status, significant comorbidities that preclude platinum chemotherapy or surgery, or inability to attend the Rome study site are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase nodal clearance rates and convert more patients to curative surgery, potentially improving long-term outcomes.

How similar studies have performed: Other neoadjuvant trials combining chemotherapy with PD-1/PD-L1 inhibitors (for example CheckMate 816) have shown higher pathological response rates and early survival signals, although use of tislelizumab specifically in this setting is less established.

Eligibility criteria

Inclusion Criteria:

* 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.
* 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.

Exclusion Criteria:

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.

Where this trial is running

Rome, Roma (RM)

• Istituti Fisioterapici Ospitalieri — Rome, Roma (RM), Italy (Recruiting)

Study contacts

• Principal investigator: Federico Cappuzzo — Istituti Fisioterapici Ospitalieri
• Study coordinator: Federico Cappuzzo, Medical Oncology

Conditions Stage III NSCLC