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

NCT07264647 | Recruiting Phase 2 DMC

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

Brief 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).

Conditions

Stage III NSCLC

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Study Arms (2)

surgery

EXPERIMENTAL

After a neoadjuvant chemoimmuno treatment patient is selected to the surgery and immuno maintenance arm if resectable

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

Drug: Tislelizumab; Radiation: Chemoradiotherapy

Interventions

surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines PROCEDURE

surgery if resectable after neoadjuvant treatment

surgery

Tislelizumab DRUG

Compared to clinical practice in Italy this trial is adding a neoadjuvant chemoimmuno treatment with adjuvant immuno

chemoradio; surgery

Chemoradiotherapy RADIATION

if patient not resectable after neoadjuvant treatment, chemoradiotherapy performed

chemoradio

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Ricerca Traslazionale: lead

Study Sites (1)

Istituti Fisioterapici Ospitalieri

Rome, Roma (RM), 00144, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tislelizumab; Surgical Procedures, Operative; Chemoradiotherapy

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)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Federico Cappuzzo

  Istituti Fisioterapici Ospitalieri

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federico Cappuzzo, Medical Oncology

CONTACT

+390652665789; federico.cappuzzo@fondazionefort.org

Study Design

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

Model Details: This is a phase 2 clinical study, monocentric and prospective.

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 4, 2025
• Study Start: March 27, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2030
• Last Updated: December 4, 2025

Record last verified: 2025-11

Locations

IT (1)