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The goal of this clinical trial is to evaluate the clinical value of ctDNA testing in guiding the optimization of immunochemotherapy cycles during induction treatment for resectable patients with NSCLC. The main questions it aims to answer are:
Advances in precision medicine have highlighted the potential of circulating tumor DNA (ctDNA) detection in NSCLC diagnosis, treatment efficacy monitoring, and prognosis evaluation. Induction immunotherapy combined with chemotherapy is now a standard treatment for patients with resectable NSCLC, but optimizing the number of immunochemotherapy cycles to enhance efficacy and reduce toxicity remains a critical clinical challenge. In this Phase II, proof-of-concept trial, around 83 patients with AJCC stage IIA-IIIB NSCLCs who are deemed resectable by an MDT team will participate to evaluate the potential role of dynamic ctDNA changes in guiding the cycle reduction of induction immunotherapy combined with chemotherapy while maintaining overall efficacy.
Eligible patients will receive 2 cycles (21-day intervals) of PD-1 inhibitor + platinum-based chemotherapy. Subsequent cycles (1-2 additional cycles) are determined by ctDNA status via tumour-agnostic strategies:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Induction immunochemotherapy | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PD-1 inhibitor | Drug | Two to four cycles of tislelizumab at a dose of 200 mg every three weeks, along with a platinum-based chemotherapy doublet based on the result of ctDNA dynamics |
| Measure | Description | Time Frame |
|---|---|---|
| MPR | MPR is defined as ≤10% residual viable tumor in the resected specimen | From date of enrollment until one month after resection |
| Measure | Description | Time Frame |
|---|---|---|
| R0 resection rate | defined as the percentage of patients that undergo R0 surgical resection after neoadjuvant treatment | From date of enrollment to an average of 18 weeks after the first dose |
| pCR rate |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy and safety comparisons between 2-cycle vs. >2-cycle groups | Efficacy (MPR, pCR [percentages]) and safety (TRAEs [percentage]) comparisons between 2-cycle vs. >2-cycle groups. | 3 months following resection |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ze-Rui Zhao, MD PhD | Contact | +86 87343317 | zhaozr@sysucc.org.cn |
| Name | Affiliation | Role |
|---|---|---|
| Ting Zhou | Sun Yat-Sen University Cancer Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510060 | China |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| D000082082 | Immune Checkpoint Inhibitors |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000074322 | Antineoplastic Agents, Immunological |
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| Platinum Doublet | Drug | Platinum-based chemotherapy (carboplatin AUC=5 + pemetrexed 500 mg/m² [adenocarcinoma] or nab-paclitaxel 260 mg/m² [squamous/other subtypes]) |
|
PCR rate is defined the percentage of patients with no residual viable tumor in the resected specimen
| From date of enrollment until one month after resection |
| 24-month EFS | 24-month event-free survival rate in ITT population, defined as the interval between the start of neoadjuvant treatment and any progression of disease precluding surgical resection, progression of disease in the absence of surgery, progression or recurrence after surgery, or death from any cause, whichever occurred first | 36 months following initial treatment |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |