Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) calculations further confirmed that yibeinoside A and vomicine had better binding free energies than lorlatinib. Collectively, these findings suggest that yibeinoside A, with its balanced binding interactions and favorable predicted pharmacokinetic profile, is a promising lead candidate for further development as a selective inhibitor against G2032R-mutant ROS1.

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 CROWN study demonstrated that first-line lorlatinib significantly improves progression-free survival and intracranial control compared to crizotinib, with sustained benefits observed over a follow-up period of up to 5 years. The proposed safety management framework emphasizes patient preparation and regular monitoring to predict AE occurrence, indicating AE-specific interventions, mitigation strategies and multidisciplinary collaboration to optimize outcomes. Lorlatinib's toxicity appears generally predictable and manageable; the safety framework offers pragmatic guidance to clinicians for appropriate management in clinical practice.

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=28, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

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

Repotrectinib is not cost-effective at current prices, but first-line use is consistently more economically favorable than second-line therapy. Price reductions or shorter treatment durations could improve its cost-effectiveness.

The patient was initially treated with alectinib, but experienced rapid disease progression. After repeat genetic testing, therapy was switched to lorlatinib, which again resulted in early progression...To our knowledge, this is the first reported case of ivonescimab use in such a patient. This case offers a potential reference for the management of ALK fusion-positive lung adenocarcinoma resistant to ALK tyrosine kinase inhibitors (ALK-TKIs).

Lorlatinib, a third-generation ALK TKI, achieved 1L indication on March 3, 2021, but is generally associated with adverse events including weight gain in up to 44% of patients from the recent update of the CROWN study; hence its use as 1L treatment has lagged behind alectinib. Here, we report a patient's case who had gained significant weight during still on-going 12-year treatment with alectinib and achieved weight loss through semaglutide but discontinued several months after starting semaglutide due to acute gallstone pancreatitis requiring emergency cholecystectomy. We believe this is the first case report on the efficacy and potential adverse events of GLP-1 agonist in treating the weight gain induced by alectinib.

At 2 years of follow-up, the patient remains on lorlatinib therapy without recurrence and demonstrates excellent hand function despite moderate scar contractures. This case highlights the efficacy of neoadjuvant therapy combined with resection in managing infantile fibrosarcoma-like tumors.

P2, N=70, Active, not recruiting, CStone Pharmaceuticals | Trial completion date: Nov 2025 --> May 2026