ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

P2, N=33, Completed, University Health Network, Toronto | N=50 --> 33 | Recruiting --> Completed

P2/3, N=396, Not yet recruiting, Shanghai Chest Hospital

P1/2, N=358, Recruiting, Xilio Development, Inc. | Trial completion date: Feb 2027 --> Sep 2028 | Trial primary completion date: Feb 2027 --> Sep 2028

P=N/A, N=35, Completed, Pfizer | Active, not recruiting --> Completed

We present the case of a 60-year-old non-smoking woman previously treated for luminal B human epidermal growth factor receptor 2 (HER2)-positive invasive breast carcinoma with surgery, AC60 chemotherapy, trastuzumab, breast radiotherapy, and hormone therapy at the Mohammed VI Oncology Center in Casablanca, Morocco. The patient received neoadjuvant vinorelbine-cisplatin chemotherapy followed by volumetric modulated arc therapy (VMAT) thoracic radiotherapy at 66 Gy, achieving clinical and radiological stabilization. This case highlights the occurrence of a second driver-negative primary lung adenocarcinoma in a non-smoker and underscores the importance of integrated histopathological, immunohisto chemical, and targeted molecular evaluation in distinguishing primary tumors from metastases, as well as the potential role of post-therapeutic carcinogenesis.

P1/2, N=121, Active, not recruiting, Precision Biologics, Inc | Recruiting --> Active, not recruiting | Trial completion date: Jan 2029 --> Nov 2026 | Trial primary completion date: Jan 2028 --> Jun 2026

We report the case of a 61-year-old woman diagnosed with stage IV lung adenocarcinoma with brain metastasis harboring an EGFR exon 19 deletion (p.E746_A750del), who acquired resistance to osimertinib through a ROS1 fusion bypass pathway. The patient achieved a survival of over 6.5 years from initial diagnosis through ongoing adjustments to targeted therapy, including sequential treatment with crizotinib, entrectinib, and lorlatinib...Notably, we observed an interesting phenomenon with both crizotinib and entrectinib: while initial treatment led to intolerable adverse reactions requiring discontinuation, subsequent reintroduction of the same agent was well-tolerated. This case report aims to provide potential treatment strategies for patients with similar complex co-mutations.

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.