ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

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.

This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced ROS1-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.

Key differences in [Formula: see text] interactions at they cytosolic end of TM7 between active and inactive states were identified due to the reorganisation of the DPxxY motif. Finally, GnRH1R communication with lipids through hydrogen bonds involving R240[Formula: see text], R75[Formula: see text], and S140[Formula: see text] was observed. This study provides insights into the active conformation and binding dynamics of the GnRH-GnRH1R complex, advancing our current understanding by providing a coherent picture that consolidates previous interpretations, thereby paving the way to better therapeutic applications.

This case report identifies a novel SNX25-ROS1 fusion mutation in NSCLC, showing strong sensitivity to ROS1-targeted therapy. It highlights the importance of molecular profiling in detecting rare genetic alterations and underscores the therapeutic potential of targeted treatments for NSCLC with unique molecular subtypes.

These alterations were mutually exclusive with common drivers such as EGFR or KRAS. Detection of rare fusions highlights the therapeutic potential of comprehensive NGS profiling in Romanian NSCLC patients.

P2, N=100, Active, not recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Trial primary completion date: Sep 2025 --> Apr 2028

Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. In this nonrandomized clinical trial, lorlatinib demonstrated durable efficacy and manageable safety in TKI-naive advanced ROS1-positive NSCLC, supporting the potential for using lorlatinib in earlier treatment settings. ClinicalTrials.gov Identifier: NCT03612154.

Crizotinib first demonstrated substantial clinical benefit, but its limitations, including poor central nervous system (CNS) penetration and acquired resistance, highlighted the need for next-generation inhibitors. Several agents have since been developed, including entrectinib, lorlatinib, repotrectinib, taletrectinib, and zidesamtinib, each offering improved intracranial (IC) activity and efficacy against resistance mutations, notably ROS1^G2032R. Despite these advances, optimal sequencing strategies remain undefined, and resistance ultimately emerges in most patients. This review provides an updated overview of ROS1 biology, diagnostic approaches, clinical outcomes with currently available TKIs, mechanisms of resistance, and ongoing challenges, emphasizing the rapidly evolving therapeutic landscape.

P1, N=22, Active, not recruiting, National Cancer Institute (NCI) | N=85 --> 22 | Trial completion date: Jun 2026 --> Nov 2026 | Trial primary completion date: Jun 2026 --> Nov 2025

P=N/A, N=535, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Apr 2025 | Trial primary completion date: Sep 2025 --> Apr 2025

The safety profile of crizotinib remained consistent with previous reports, with most adverse events being grade 1 or 2 and no new safety concerns identified. This analysis supports the efficacy of crizotinib in patients with advanced NSCLC and ROS1 rearrangements, although its activity in patients with BM remains limited, highlighting the need for brain-penetrant tyrosine kinase inhibitors to improve outcomes in this patient group.