ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

Crizotinib showed limited efficacy with a median progression-free survival of 3.5 months. These findings highlight indolent disease behavior but limited TKI benefit, supporting the need for adjuvant trials.

TACTI-004 will evaluate whether efti can mitigate resistance to ICIs when added to SoC in NSCLC, irrespective of PD-L1 tumor status. www.clinicaltrials.gov identifier is NCT06726265.

These findings underscore the importance of routine cardiovascular monitoring, particularly in older patients and those with atrial arrhythmias.

EGFR and ALK alterations confer favorable outcomes, while certain alterations such as ROS1 and ERBB2 associate with poorer survival. These findings support the routine integration of biomarker testing into NSCLC management and highlight the need for biomarker-specific therapeutic approaches.

Currently, selpercatinib, larotrectinib, and repotrectinib are approved by the FDA for the treatment of certain solid tumors harboring specific gene fusions. Recent studies on zenocutuzumab resulted in the FDA-accelerated approval for NGR1 fusion-positive NSCLC and PDAC. Germline mutations may specifically increase responsiveness to poly(ADP-ribose) polymerase (PARP) inhibitors or platinum-based treatments. Comprehensive genomic profiling, incorporating fusion detection and germline testing, is essential to identify patients who may benefit from precision-based approaches.

Additional discussion includes advancements in therapies directed at MET, HER2, RET, ROS1, and FGFR alterations-each representing promising targets in NSCLC. This review concludes by exploring the growing evidence surrounding TROP-2 as a novel therapeutic target, especially relevant in cases where previous targeted treatments have failed.

P1, N=168, Completed, AbbVie | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Sep 2025 | Trial primary completion date: Jun 2025 --> Sep 2025

P1/2, N=161, Completed, Takeda | N=109 --> 161

First-generation tyrosine kinase inhibitors (TKIs) such as crizotinib displayed significant early reactions but faced challenges due to restricted central nervous system (CNS) penetration and mutation resistance, while entrectinib and larotrectinib expanded treatment options but also experienced resistance...Safety data shows an acceptable toxicity profile, mainly featuring gastrointestinal and hepatic adverse effects, with fewer neurocognitive side effects compared to lorlatinib...Current trials and regulatory activities in China, the U.S., and other locations demonstrate taletrectinib's growing clinical significance. Taletrectinib's well-rounded pharmacological attributes of systemic action, intracranial effectiveness, resistance range, and tolerability render it an intriguing enhancement to the framework of precision oncology.

The addition of serplulimab to chemotherapy led to significantly longer progression-free survival in patients with locally advanced or metastatic non-squamous NSCLC compared with chemotherapy alone and represents an alternative first-line treatment option for this patient population. HLX04 plus serplulimab and chemotherapy did not confer further statistical benefit compared with serplulimab plus chemotherapy.

P3, N=614, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

Furthermore, this case describes a rare presentation of a ROS1 alteration in SCC of the lung. This illustrates the importance of routine comprehensive genomic profiling in lung cancer patients regardless of histology and smoking status.