Chemoembolization, Therapeutic, Chemotherapy, Conversion Therapy, Tislelizumab, Unresectable Stage III Non-small Cell Lung Cancer
Conditions
Keywords
Unresectable Non-Small Cell Lung Cancer, Tislelizumab, Chemotherapy, Bronchial Artery Chemoembolization, Conversion Therapy
Brief summary
The goal of this phase 2 trial is to evaluate the efficacy and safety of tislelizumab combined with intravenous chemotherapy and bronchial artery chemoembolization (BACE) as conversion therapy for patients with initially unresectable stage IIIA-IIIB non-small cell lung cancer (NSCLC). The main questions it aims to answer are: * What is the 1-year event-free survival (EFS) rate with this treatment? * Can this treatment improve tumor response and the chance of curative-intent resection? * What adverse events occur during treatment? Participants will receive tislelizumab, intravenous chemotherapy, and BACE for up to 4 cycles. Tumor response and resectability will be evaluated by imaging and multidisciplinary team (MDT) assessment every 2 cycles. Participants who become resectable may undergo surgery followed by postoperative treatment per protocol. Participants who remain unresectable after 4 cycles will receive guideline-recommended chemoradiotherapy followed by tislelizumab consolidation. Regular follow-up will be performed for efficacy and safety assessment.
Interventions
DRUGTislelizumab
Tislelizumab 200 mg is administered intravenously on Day 0 of each 21-day cycle for up to 4 cycles. Postoperative or consolidation tislelizumab may be given according to protocol-defined treatment pathways.
Intravenous chemotherapy is administered on Day 1 of each 21-day cycle for up to 4 cycles. Patients with lung squamous cell carcinoma receive albumin-bound paclitaxel, and patients with lung adenocarcinoma receive pemetrexed. Carboplatin is administered intra-arterially during BACE in cycles with the procedure; if BACE is not performed in a given cycle, carboplatin is administered intravenously on the same day per protocol.
PROCEDUREBronchial Artery Chemoembolization (BACE)
BACE is performed on Day 1 of the first 21-day treatment cycle using intra-arterial carboplatin infusion followed by embolization with 300-500 μm blank microspheres. Subsequent BACE procedures are performed on demand, based on tumor response on contrast-enhanced chest CT and multidisciplinary team (MDT) evaluation. The total number of BACE procedures ranges from 1 to 4.
Sponsors
Sichuan Cancer Hospital and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 years * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) * Newly diagnosed, previously untreated stage IIIA-IIIB NSCLC according to the 9th edition TNM staging system * Initially unresectable disease as determined by multidisciplinary team (MDT) assessment * At least 1 measurable intrapulmonary lesion according to RECIST version 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Forced expiratory volume in the first second (FEV1) \> 1.0 L and \> 40% of predicted normal value * Estimated life expectancy of at least 3 months * Adequate organ function * Willingness to provide tumor tissue for pathology, molecular testing, and PD-L1 assessment before enrollment * Women of childbearing potential must have a negative pregnancy test within 72 hours before the first dose and agree to use effective contraception during the study and for 3 months after the last dose of tislelizumab * Men with partners of childbearing potential must agree to use effective contraception during the study and for 3 months after the last dose of tislelizumab * Ability to understand and willingness to sign a written informed consent form
Exclusion criteria
* Prior local therapy for NSCLC, including radiotherapy or interventional therapy * Known positive driver genomic alterations, including EGFR mutations, ALK rearrangements, ROS1 rearrangements, and MET exon 14 skipping alterations * Distant organ metastasis * History of another malignancy within the past 5 years * Active autoimmune disease or history of autoimmune disease requiring systemic treatment * Known allergy to any study drug or excipient * Interstitial lung disease, non-infectious pneumonitis, chronic obstructive pulmonary disease, or other uncontrolled systemic diseases judged to interfere with study treatment * Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy, including active tuberculosis * Major surgery requiring general anesthesia within 4 weeks before first dose * Any medical condition, alcohol or drug abuse, or dependence that may interfere with study treatment, interpretation of results, or increase treatment risk * Participation in another interventional therapeutic clinical study * Psychiatric illness or history of psychotropic drug abuse that may compromise study participation * Any condition judged by the investigator to make the patient unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-Year Event-Free Survival (EFS) Rate | 1 year after the first dose of study treatment | The proportion of participants who remain event-free at 1 year after the first dose of study treatment. Events include radiographic disease progression according to RECIST 1.1, failure to complete the planned surgery for any reason, postoperative recurrence, or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R0 Resection Rate | Up to approximately 20 weeks after the first dose of study treatment | The proportion of participants who undergo curative-intent surgery and achieve microscopically margin-negative (R0) resection after conversion treatment. |
| Objective Response Rate (ORR) | Up to approximately 30 months after the first dose of study treatment. | The proportion of evaluable participants who achieve a complete response (CR) or partial response (PR) according to RECIST version 1.1 based on center imaging assessment. |
| Pathologic Complete Response (pCR) Rate | At the time of surgery, up to approximately 20 weeks after the first dose of study treatment. | The proportion of participants who undergo surgery and have no residual viable tumor cells in the resected primary tumor and all resected lymph nodes. |
| Major Pathologic Response (MPR) Rate | At the time of surgery, up to approximately 20 weeks after the first dose of study treatment. | The proportion of participants who undergo surgery and have 10% or less residual viable tumor cells in the resected primary tumor. |
| Event-Free Survival (EFS) | From the first dose of study treatment up to approximately 30 months | Time from the first dose of study treatment to the first occurrence of radiographic disease progression according to RECIST 1.1, failure to complete the planned surgery for any reason, postoperative recurrence, or death from any cause. Participants without an event will be censored at the date of last follow-up. |
| Overall Survival (OS) | From the first dose of study treatment up to approximately 30 months. | Time from the first dose of study treatment to death from any cause. Participants who are lost to follow-up or alive at the end of study follow-up will be censored at the last known date alive. |
| Incidence of Adverse Events | From the first dose of study treatment up to approximately 30 months. | Incidence, severity, relationship to study treatment, and outcomes of adverse events assessed according to NCI-CTCAE version 5.0. |
Countries
China
Contacts
CONTACTXuegang Yang, MD
PRINCIPAL_INVESTIGATORXuegang Yang, MD
Sichuan Cancer Hospital and Research Institute
STUDY_CHAIRGuohui Xu, MD
Sichuan Cancer Hospital and Research Institute
Outcome results
None listed