ALK mutation

P2, N=70, Recruiting, Innate Pharma | Trial completion date: Sep 2026 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Jun 2027

High-risk tumors were enriched for translational and ribosome biogenesis pathways, whereas low-risk tumors were enriched for adaptive immune activation programs. Cross-context transcriptomic integration identified a minimal ALK-associated three-gene signature that reproducibly predicts NB outcomes and reflects distinct underlying biological states, supporting its potential value for risk stratification and hypothesis-driven therapeutic development.

These findings were consistently validated using flow cytometry in an independent cohort. Distinct immune cell profiles highlight elevated baseline CXCR3+ CD127+ effector CD8+ T cells predicting favorable outcomes and impaired cDC-CD4+ T cell dynamics as critical contributors to anti-PD-1/PD-L1 resistance in MT-NSCLC.

This study demonstrates very high molecular concordance between primary lung adenocarcinomas and their synchronous pleural or intrapulmonary metastases. The observed 100% concordance of actionable driver alterations across paired specimens supports the clinical reliability of thoracic metastatic biopsies for baseline molecular profiling in treatment-naïve disease. Although limited by sample size, these findings support the biological stability of actionable driver alterations during early thoracic metastatic dissemination.

Baseline frequencies of peripheral CD4⁺ T TIGIT⁺ and CD8⁺ TEMRA cells were independently associated with survival outcomes in advanced NSCLC patients receiving first-line ICI-based therapy, suggesting that peripheral T cell immunophenotyping at treatment initiation may provide prognostic information beyond conventional biomarkers. Further studies incorporating external validation in independent cohorts, longitudinal immune profiling, and deeper T cell subset characterization are warranted to validate these findings and to elucidate the immune dynamics underlying treatment response and resistance.

ACT was not significantly associated with improved RFS for stage IA LUADmp patients postoperatively. This study was registered at ClinicalTrials.gov: NCT03351842.

Future strategies should prioritize multicenter validation, integration of chronobiological profiling, and exploration of combination therapies. Cost-effectiveness analyses, awareness campaigns, and clinical drives to evaluate safety and adherence will be essential to establish trust and optimize outcomes.

This study suggests that common molecular alterations in lung cancer exhibit prognostic value within specific stages, and notably, TP53, KRAS and ALK alterations hold the potential to modify the current staging system. These findings provide a valuable reference for the forthcoming 10th Edition TNM staging system.

P1, N=5, Terminated, Genprex, Inc. | Phase classification: P1/2 --> P1

For EGFR-mutant NSCLC, sequential development of tyrosine kinase inhibitors (TKIs) from first- to third-generation agents-culminating in osimertinib-has markedly improved survival. Similarly, successive generations of ALK inhibitors, including alectinib, brigatinib, and lorlatinib, have extended disease control, particularly within the central nervous system. The introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan for HER2-mutant NSCLC, and emerging TKIs like zongertinib, represent new therapeutic milestones...Beyond lung cancer, our group, in collaboration with Juntendo University ARO (academic research organization) and fifteen institutions in Japan, conducted the MARBLE phase II trial of atezolizumab plus chemotherapy for thymic carcinoma, achieving a 56% objective response rate and 9.6-month median progression-free survival, supporting potential ICI approval in Japan...The DLL3-targeted BiTE tarlatamab significantly improved overall survival to 13.6 months in the phase III DeLLphi-304 trial for relapsed SCLC, with manageable cytokine release syndrome. Collectively, these advances signify a shift toward biologically driven, molecular-targeted or immune-integrated therapy, aiming to transform lung cancer into a chronic, manageable disease in the future, hopefully.

In CRC, TAT was 4.1, 5.3, and 10.2; QNS 0%, 0%, 7.5%; detection 63.9%, 62.5%, and 57.1%. OPA provides faster TAT and lower QNS rates with comparable detection of actionable alterations, supporting its use for community-based molecular testing in NSCLC and CRC.

This study enriches the current volume of evidence on histopathologic, genetic, immunologic correlates of PD-L1 expression and, to our knowledge, is the first comprehensive analysis of arm-level alterations. Further studies are warranted to validate these finding and to determine their associations with clinical outcomes.