ROS1 rearrangement

Dirozalkib exhibited favorable safety, antitumor activity and pharmacokinetics in patients with advanced ALK-rearranged NSCLC. The recommended phase II dose was 500 mg/day.

The prevalence and prognostic significance of STAS varied by driver mutation status, suggesting that the clinical interpretation of STAS may depend on the molecular context.

This case highlights the potential of ROS1 as a therapeutic target in SCC, which has historically been considered rare, as ROS1-rearranged SCC accounts for only 0.2% according to the Foundation Medicine database. This underscores the importance of incorporating NGS into clinical practice, particularly for never smokers/light smokers or patients with advanced SCC of the lungs, to identify targetable mutations and guide personalized therapy.

P2, N=534, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2025 --> May 2026

The landmark LAURA and POLESTAR studies have established a standard therapeutic model involving targeted consolidation therapy with osimertinib or aumolertinib after definitive chemoradiotherapy for NSCLC patients harboring EGFR-sensitive mutations. Through multiple rounds of comprehensive discussion and expert voting, this consensus was jointly developed. It provides evidence-based recommendations addressing frequently encountered clinical questions regarding unresectable stage III driver-positive NSCLC, aiming to serve as a key reference for clinical practice.

P3, N=1200, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

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.

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.

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.

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.

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.

P1/2, N=862, Recruiting, DualityBio Inc. | Trial completion date: Jan 2028 --> May 2028 | Trial primary completion date: Sep 2027 --> Dec 2027