ROS1 rearrangement

The overall concordance of genotyping results between cfRNA-protected SS and paired CNB specimens was 100%, correctly identifying all ALK fusions, ROS1 rearrangements, and MET-14 skipping alterations. These findings highlight that preserving cfRNA in CNB-SS from NSCLC can improve the performance of genomic testing, particularly for RNA-based assays, without compromising the accuracy of DNA-based assays.

P1/2, N=80, Completed, Institut Bergonie | Active, not recruiting --> Completed

Here, we report a lung IMT in a 45-year-old female demonstrating a unique meningothelial-like pattern, equivocal ALK expression (negative for clone 5A4 and positive for clone ALK1), negative ALK rearrangement by FISH, and the presence of the TPM3::ALK fusion. To our knowledge, this is the first reported case of lung IMT displaying meningothelial-like whorls, with a particular focus on differential diagnosis.

Multiple ROS1 tyrosine kinase inhibitors (TKIs)-from crizotinib to newer agents such as entrectinib, lorlatinib, repotrectinib, taletrectinib, and the highly selective zidesamtinib-have improved systemic and intracranial outcomes, although resistance remains inevitable and biologically diverse, involving both on-target kinase mutations and off-target mechanisms...Pemetrexed-based chemotherapy remains an effective option, whereas immune checkpoint inhibitors provide limited benefit...Looking ahead, priorities include optimizing sequencing strategies, evaluating perioperative targeted approaches, and incorporating genomic monitoring to anticipate resistance. These advances are reshaping the natural history of ROS1-rearranged NSCLC and supporting a more durable, precision-driven treatment paradigm.

Regimens co-targeting the MAPK pathway and ALK or ROS1 had limited efficacy in unselected patients with lorlatinib-resistant NSCLC, underscoring the need for more effective and biomarker-informed treatment strategies.

The efficacy of crizotinib in this molecular subset demonstrates favorable clinical outcomes. Furthermore, considering the relatively high prevalence of ROS1 co-mutations with other genetic alterations in these cases, multi-targeted combination therapy may represent a promising therapeutic strategy for this distinct patient population.

P2, N=80, Recruiting, Stanford University | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=16, Terminated, Rutgers, The State University of New Jersey | Active, not recruiting --> Terminated; accrual goal met

P2, N=107, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

The progression modes of ROS1 rearrangement may predict survival benefits and provide subsequent treatment strategies in ROS1-rearranged NSCLC.

P3, N=131, Recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci