Xalkori (crizotinib)

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.

103 patients (95.4%) received ≥1 line of systemic anticancer therapy (SACT), of which 65 (63.1%) received first-line targeted therapy, mostly crizotinib monotherapy (n = 45) or crizotinib-based regimens (n = 10), with a median (95% CI) rwPFS and OS of 14.0 (8.3-19.8) and 47.9 (27.3-not estimable) months, respectively...Results from this study indicated a tendency for longer survival using currently available ROS1-targeted versus non-targeted therapy for patients with ROS1-positive advanced NSCLC. Nevertheless, survival outcomes were limited, highlighting the importance of more effective emerging treatments for ROS1-positive disease.

Our report underscores the critical need for rigorous thromboembolic monitoring in pregnant patients undergoing cancer treatment. Furthermore, we provide evidence that placental tissue significantly reduces fetal crizotinib exposure, suggesting that crizotinib might be a viable therapeutic option for maintaining a pregnancy during lung cancer treatment.

This TPR-ALK fusion-driven IMT demonstrates that disease progression after an initial response to crizotinib can be effectively overcome with lorlatinib, resulting in rapid and durable clinical benefit. These findings add to emerging evidence supporting next-generation ALK inhibitors as effective treatment options for ALK-rearranged IMT after crizotinib failure.

We present a patient with Anaplastic lymphoma kinase (ALK) fusion lung adenocarcinoma who received sequential treatment with ALK tyrosine kinase inhibitor (TKI) (crizotinib, PFS:32.3 months and then conteltinib, PFS: 29 months). Subsequently, the patient switched to third generation EGFR-TKI treatment with almonertinib. This case suggests EGFR mutation is one of the mechanisms of ALK-TKI resistance, highlights the value of re-biopsy in identifying potentially targetable resistance mechanisms and underscores the spatiotemporal heterogeneity of tumors under the selective pressure of ALK-TKI.

P2, N=20, Active, not recruiting, National Cancer Institute (NCI) | N=35 --> 20 | Trial completion date: Feb 2026 --> Dec 2026

P2, N=44, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Dec 2026