Analysis of Deoxyribonucleic Acid and Ribonucleic Acid Next-Generation Sequencing in Non-Small Cell Lung Cancer Patients Without Pathological Complete Response Following Neoadjuvant Immunotherapy

Not yet recruiting

• Conditions: NSCLC

• Registration Number: NCT07179445
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

This multicenter, retrospective cohort study plans to enroll patients with lung adenocarcinoma who received neoadjuvant immunotherapy prior to surgery and did not achieve pathological complete response (non-pCR) upon postoperative pathological evaluation. Using Deoxyribonucleic Acid(DNA) and Ribonucleic Acid(RNA) next-generation sequencing (NGS), the investigators aim to detect driver genetic alterations to investigate the real-world frequency of driver gene positivity in postoperative samples from patients with lung adenocarcinoma-whose EGFR and ALK status had been previously excluded via pathological complete response(pCR) or DNA-based next-generation sequencing-yet still did not attain pathological complete response(pCR) after neoadjuvant immunotherapy. Additionally, the study will characterize the driver-positive patient subgroup and compare the efficacy of postoperative adjuvant immunotherapy between driver-positive and driver-negative populations.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-07
• Study First Submitted QC: 2025-09-14
• Last Update Submitted: 2025-09-14
• Study First Posted: 2025-09-17
• Last Update Posted: 2025-09-17
• Study Start: 2025-09-20
• Primary Completion: 2026-01-31
• Study Completion: 2026-05-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Aged 18 years or older, regardless of sex.
• Pathologically confirmed, resectable non-small cell lung cancer (NSCLC); having received neoadjuvant therapy containing immune checkpoint inhibitors prior to surgery; without achieving pathological complete response (non-pCR) upon postoperative pathological assessment.
• Molecular characteristics: Pre-treatment biopsy specimens tested negative for EGFR mutations and ALK fusions by DNA-based NGS or PCR methods.
• Sample requirements: Availability of 5-10 formalin-fixed, paraffin-embedded (FFPE) sections prepared from surgical tissue specimens, with ≥5% tumor cell content confirmed by H&E staining.

Exclusion Criteria

• Failure to meet any one of the requisite eligibility criteria specified in the inclusion criteria.
• History of a concurrent or prior malignancy at other sites.
• Failure to complete the planned cycles of neoadjuvant immunotherapy due to treatment-related toxicities.
• Any other condition that, in the judgment of the investigator, renders the patient unsuitable for participation in this study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of driver-alteration-positive patients detected by combined DNA+RNA testing	through study completion, an average of 1 year	We selected patients with lung adenocarcinoma who had received preoperative neoadjuvant immunotherapy, did not achieve pathological complete response (pCR) after surgery, and had pre-treatment biopsy samples testing negative for EGFR and ALK alterations. Subsequent combined DNA/RNA next-generation sequencing (NGS) was performed using the 3DMed Onco™ Core Tissue Detection Kit. The proportion of patients with identified driver genomic alterations served as the primary endpoint of the study.

Secondary Outcome Measures

Name	Time	Method
Comparative Analysis of Adjuvant Immunotherapy Efficacy Between Driver-Alteration-Positive and Negative Cohorts	through study completion, an average of 1 year	For the comparison between driver gene-positive and negative populations: Disease-Free Survival (DFS) will be compared between patients who received adjuvant immunotherapy and were driver gene-positive versus those who were driver gene-negative. DFS is defined as the time from surgery to the first occurrence of disease recurrence, distant metastasis, or death from any cause.
Stratified Analysis of EGFR/ALK-Positive Versus Other Driver-Alteration-Positive Subgroups	through study completion, an average of 1 year	For the stratified analysis among positive populations: Among the driver gene-positive patients who received adjuvant immunotherapy, a stratified analysis will be performed comparing patients with EGFR or ALK mutations versus those with mutations in other driver genes (e.g., ROS1, BRAF V600E, MET, RET, etc.).

Trial Locations

Locations (1)

Tianjin Medical University Cancer Institute and Hospital(Lead Center); 🇨🇳 Tianjin, China