Xalkori (crizotinib)

P1, N=24, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

The combination of osimertinib and crizotinib resulted in a marked clinical and metabolic response, was well tolerated, and the patient remained in remission. This rare case highlights that acquired CD74-ROS1 fusions may contribute to osimertinib resistance and suggests that combination targeted therapy may represent a potential therapeutic approach in selected patients.

P3, N=194, Recruiting, Nuvation Bio Inc. | N=138 --> 194

We constructed and verified a four-gene ORS-based prognosis model for GBM, linking replication stress to immune evasion and drug sensitivity for the first time. Experimental validation confirmed the pro-tumorigenic role of PDCL3, offering potential biomarkers and therapeutic targets.

Disproportionality analyses were performed using four algorithms-Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS)-to detect adverse event signals for crizotinib, alectinib, and brigatinib. All three ALK-TKIs demonstrate distinct, generation-dependent safety profiles characterized by early-onset hepatobiliary and pulmonary toxicities, with evident sex-specific differences in organ susceptibility. Intensive safety monitoring during the initial 12 weeks of therapy is essential for preventing severe outcomes.

Subgroup analysis showed that the adverse effect of V3 was more pronounced in patients treated with crizotinib (HR = 1.40, 95%CI: 1.00-1.96, p=0.049), in the first line treatment setting (HR = 1.83, 95%CI: 1.34-2.50, p<0.001), and in those assessed by NGS (HR = 1.67, 95%CI: 1.34-2.08, p<0.001). A significant association was also observed in the brigatinib-treated population (HR = 2.09, 95%CI: 1.33-3.28, p=0.001), although this finding was based on only two studies...Prospective studies with standardized molecular subtyping are still needed before considering clinical stratification based on ALK variant types. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251229641, identifier CRD420251229641.

Oncogenic RET gene rearrangements drive a subset of lung adenocarcinomas (LUAD) and the tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib are approved therapeutics. By contrast, upfront treatment with selpercatinib and crizotinib in orthotopic tumors yielded complete elimination of 7 of 9 TR.1 tumors and both deepened and prolonged the duration of response in TR.2 tumors. The findings provide new insight into mechanisms of acquired resistance through bypass signaling and highlight the therapeutic benefit of simultaneous upfront blockade of driver oncogenes and dominant resistance mechanisms in LUAD.

This over-a-decade-long clinical development program led to the commercialization of a palatable, dose-flexible, oral solid multiparticulate pediatric formulation of crizotinib for patients with anaplastic large cell lymphoma or inflammatory myofibroblastic tumors. The clinical outcomes and development strategy described herein provide a practical framework to support future pediatric formulation development programs.

Small-molecule ALK inhibitors, including crizotinib, have demonstrated high overall response rates (67%-88%) and complete remission rates (~60%-80%) in relapsed or refractory ALK-positive ALCL, often with rapid clinical responses...In addition, it explores emerging strategies for integrating ALK inhibitors into precision-based management of T-cell lymphomas, including combination approaches with chemotherapy, immunotherapy or antibody-drug conjugates. Collectively, these developments highlight a paradigm shift towards biology-driven, personalized therapy in ALK-positive ALCL.

P=N/A, N=97, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | Trial completion date: Mar 2027 --> Nov 2026 | Trial primary completion date: Mar 2027 --> Nov 2026

The patient received treatment with crizotinib and entrectinib successively. No new severe drug-related adverse events were observed. This case suggests that in patients with ROS1 fusion-positive nonsmall cell lung cancer who have experienced prior ROS1-tyrosine kinase inhibitor treatment failure and concomitant severe renal insufficiency, repotrectinib may represent a potential and tolerable treatment option when fully assessing clinical risks and ensuring close monitoring.