Xalkori (crizotinib)

This includes work that led to the FDA approvals of immune checkpoint inhibitors in multiple rare pediatric tumor types, the NTRK inhibitors larotrectinib, entrectinib, and repotrectinib for children and adults with solid tumors with NTRK fusions, the ALK inhibitor crizotinib in children and adults with ALK-positive inflammatory myofibroblastic tumors, and the radioligand LUATHERA for adolescents and adults with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Despite these advances, the study of rare pediatric cancers faces multiple challenges including a limited number of patients for efficient and well-powered clinical trials and a dearth of financial incentives. Ongoing, coordinated efforts are needed to continue the advancement of novel treatments and improve survival and minimize late effects.

This study is by far the most comprehensive systematic review and meta-analysis on HRQoL among ALK-positive NSCLC patients treated with ALK-TKIs. These findings extended prior literature by conducting a granular comparison of all available ALK-TKIs across multiple endpoints and highlighted the improved performance of next-generation ALK-TKIs in enhancing HRQoL for ALK-positive NSCLC patients.

These patients also showed heightened sensitivity to several chemotherapeutic and targeted agents, including Cisplatin and Crizotinib. Integrating single-cell sequencing, MR-based causality, clinical validation, and functional experiments, we identified ASPH and PTTG1 as key regulators of LUAD angiogenesis and immune evasion. These findings substantiate ASPH/PTTG1 as promising biomarkers and therapeutic targets, offering new insights into precision therapies integrating anti-angiogenic and immunomodulatory strategies.

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.

Initial treatment with chemoimmunotherapy was complicated by hypersensitivity reactions to nivolumab and paclitaxel, leading to a brief hospitalization...This case demonstrates the efficacy of neoadjuvant alectinib in managing ALK-mutant stage III lung adenocarcinoma, highlighting the potential benefits of targeted therapy in the neoadjuvant setting. Further studies are needed to establish optimal treatment protocols for patients with ALK-positive lung cancer.

The IC50 values of docetaxel, oxaliplatin, crizotinib and osimertinib were lower in HCC cases with a high-risk score. Downregulation of MCT1 inhibited the proliferation, migration and invasion of HCC cells and promoted the apoptosis of HCC cells. In conclusion, the present study developed a novel GRS for HCC, serving as an indicator for predicting clinical outcomes and responses to immunotherapy.

P3, N=200, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Oct 2025 --> May 2026 | Trial primary completion date: Oct 2025 --> May 2026

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.

Our results confirm that cell surface NCL is a biomarker and a potential target for NB, paving the way for further investigations aimed at the future clinical translation of innovative combination strategies against NB.

P3, N=190, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Mar 2027 --> Mar 2026

MET amplification has been identified as a potential therapeutic target, but resistance to MET inhibitors, such as crizotinib, remains a significant challenge...Our findings suggest that acquired resistance to MET inhibitors in MET-amplified HCC may involve clonal evolution and activation of compensatory signaling pathways. These insights highlight the need for dynamic molecular surveillance and the development of strategies targeting multiple pathways to overcome resistance and improve patient outcomes.