ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

P=N/A, N=305, Active, not recruiting, Shanghai Chest Hospital | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Dec 2027 | Trial primary completion date: Mar 2025 --> Dec 2026

P2, N=39, Recruiting, University of Chicago | Not yet recruiting --> Recruiting

This review highlights indole scaffold as a core pharmacophore for multitargets against the NSCLC like EGFR, ALK/ROS1 and VEGFR. This review helps the medicinal chemist and other researchers to develop more indole-based molecules for muti kinase targets.

Pathway-focused treatments for non-smokers, environmental interventions, and exposure-informed risk models are some potential future possibilities. Research, prevention, and patient treatment are improved worldwide when LCNS is framed as a unique, environmentally driven illness.

P2, N=45, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: May 2028 --> May 2027

P1/2, N=155, Completed, Pfizer | Active, not recruiting --> Completed

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.

The rate of bone metastasis was significantly higher in ROS1 rearrangement-positive than in ROS1 rearrangement-negative patients. ROS1 rearrangement plays a significant prognostic role in advanced progression of LUAD; however, the generally favorable survival outcomes of early-stage LUAD may obscure its prognostic value.

With 5-year follow-up, cemiplimab plus chemotherapy continues to show durable long-term efficacy benefits versus chemotherapy with consistent safety profile, as first-line therapy for advanced NSCLC.

P3, N=740, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting | Trial completion date: Apr 2028 --> Mar 2032 | Trial primary completion date: Feb 2028 --> Mar 2030

In this cohort of surgically resected NSCLC, preoperative corrected serum calcium and smoking exposure were more closely associated with tumor metabolic activity than with specific molecular alterations. These findings suggest that simple clinical and biochemical parameters may provide complementary information, although their utility for discriminating individual molecular subgroups appears limited.

Serplulimab plus chemotherapy significantly prolonged OS and maintained PFS benefit compared to chemotherapy; however, the addition of bevacizumab biosimilar HLX04 did not yield further improvement for the first-line treatment of nsq-NSCLC without EGFR or ALK/ROS1 genetic alterations. Trial registration: This trial was registered at ClinicalTrials.gov (NCT03952403, date of registration: 2019 May 14).