ALK positive

P1, N=12, Terminated, Henan Cancer Hospital | Phase classification: P1/2 --> P1 | Trial completion date: Feb 2025 --> Aug 2025

This presentation aligns with a case reported in Japan, describing severe hemolytic anemia with morphological changes in erythrocytes under alectinib treatment. This is the first report describing a rapid increase in hemoglobin after pausing alectinib and no relapse of hemolysis after switching to lorlatinib, while the lung cancer remained stable (stable disease).

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.

The mechanism of lorlatinib-induced hyperglycemia is unclear but may involve reduced insulin secretion. This case underscores the importance of monitoring for hyperglycemia in patients receiving lorlatinib, even in the absence of pre-existing diabetes, to enable early detection and prevent life-threatening complications like DKA.

P1, N=242, Active, not recruiting, ModernaTX, Inc. | Recruiting --> Active, not recruiting

P1, N=19, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 19 | Trial completion date: Mar 2043 --> Jul 2040 | Trial primary completion date: Mar 2027 --> Aug 2025

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 alterations were mutually exclusive with common drivers such as EGFR or KRAS. Detection of rare fusions highlights the therapeutic potential of comprehensive NGS profiling in Romanian NSCLC patients.

P3, N=327, Recruiting, UNICANCER | Active, not recruiting --> Recruiting | Trial completion date: Jul 2027 --> Dec 2026 | Trial primary completion date: Jan 2026 --> Dec 2026

Key advancements underscore this shift: molecularly targeted drugs (e.g., trastuzumab for HER2-positive breast cancer, EGFR and ALK inhibitors for lung cancer) have improved efficacy and reduced toxicity compared to conventional therapy...Addressing these barriers will require harmonized policies, investment in infrastructure, and educational initiatives to ensure that the promise of personalized medicine becomes accessible to all patients. Ensuring that advances are implemented responsibly-guided by pharmacological insights, supported by real-world evidence, and evaluated within ethical and economic frameworks-will be critical to realizing the full potential of personalized cancer medicine.

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 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.