Xalkori (crizotinib) / Pfizer - LARVOL DELTA

Phase 3 Trial of Crizotinib vs Observation for Surgically Resected Early-Stage ALK+ NSCLC (IASLC-WCLC 2025) - "Results : Between August 2014 and May 2024, 166 patients were enrolled in the study (of a planned sample size of 168), with enrollment stopped at the time of FDA approval of adjuvant alectinib for resected ALK+ NSCLC. Median duration of crizotinib therapy was 13.5 (IQR 3.4-23.9) months; 19 patients (22%) had crizotinib dose reductions and 21 (25%) discontinued crizotinib due to toxicities. Conclusions : Adjuvant crizotinib does not prolong DFS in resected ALK+ NSCLC."

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor

Final Biomarker and Efficacy Analyses of Lorlatinib in Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer in a Phase 2 Study. (PubMed, J Thorac Oncol) - "After 5 years of follow-up, final analyses from this phase 2 study further supported substantial activity and prolonged OS with lorlatinib in treatment-naive and previously treated patients with ALK-positive advanced NSCLC, regardless of the biomarker subgroups. Resistance mechanisms in treatment-naive patients did not include emergence of ALK mutations."

Biomarker • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4 • TP53

Patterns of Failure and Outcomes of Oligoprogression in ALK-Rearranged NSCLC Treated with ALK TKIs (ASTRO 2026) - "For first-line therapy, 130 patients (69%) received a second-generation ALK TKI, 40 (21%) received crizotinib, and 15 (8%) received lorlatinib. Oligoprogression occurs in approximately half of patients progressing on first-line ALK TKI and is enriched among those with baseline oligometastatic disease. Oligoprogressive disease was characterized predominantly by intrathoracic-only failure, a resistance pattern that may inform consolidative RT strategies. RT directed to oligoprogressive sites was associated with prolonged continuation of the same TKI, providing additional evidence for local ablative therapy in managing limited resistant disease."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4

Comparative Disproportionality Analysis of Metastatic and Neoplastic Progression Signals Associated With Crizotinib Versus Alectinib in the EudraVigilance Database (ESMO 2026) - No abstract available

Metastases • Oncology

Treatment outcomes and adverse-event related dose modifications of first generation TKIs, crizotinib and entrectinib, in advanced ROS1-rearranged NSCLC: A Canadian Real-World Study (CARMA-BROS) (ESMO 2026) - No abstract available

Adverse events • Clinical • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Crizotinib Induction Followed by CHOP-Based Chemotherapy and Consolidative ISRT in a "Sandwich" Strategy for Bulky ALK-Positive Anaplastic Large Cell Lymphoma (ASTRO 2026) - "A crizotinib-primed chemo-radiotherapy sandwich approach with consolidative ISRT achieved durable remission in bulky ALK+ ALCL, supporting an important role for ISRT in securing bulky-site control after effective systemic therapy. Toxicity was driven primarily by systemic therapy, with no evident RT-attributable adverse effects, supporting feasibility of consolidative ISRT. Dose-de-escalated ISRT (30 Gy/15 fractions) appears sufficient in this setting and warrants prospective validation."

Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALK

Darovasertib with Crizotinib vs Investigator's Choice as First-Line Treatment for Patients with HLA-A2 Negative Metastatic Uveal Melanoma (OptimUM-02): A Subgroup Analysis (ESMO 2026) - No abstract available

Clinical • Metastases • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Darovasertib and Crizotinib for HLA-A*02–Positive Metastatic Uveal Melanoma: Results from the Phase 2 OptimUM-01 Study (ESMO 2026) - No abstract available

Metastases • P2 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A

Long-Term Safety of Lorlatinib After 7 Years in CROWN: Kinetics, Management, and Correlations With Efficacy (IASLC-WCLC 2026) - P3 | "Methods : Patients were randomized 1:1 to receive lorlatinib 100 mg once daily or crizotinib 250 mg twice daily. With a mDOT of 62.6 months, AE onset and AE-related treatment modifications occurred mainly within the first 24 months, and AE-related discontinuations remained infrequent with prolonged exposure. These findings support long-term use of lorlatinib and highlight the importance of proactive AE management early in treatment to optimize sustained treatment benefit."

Clinical • Dyslipidemia • Hypertriglyceridemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

How to manage radioiodine-refractory thyroid cancer in the era of precision medicine. (PubMed, Drugs Context) - "Three multi-kinase inhibitors have been approved for this indication: lenvatinib and sorafenib as a first-line option and cabozantinib as a second-line option...Thus, additional selective inhibitors have been approved: larotrectinib and entrectinib for NTRK + tumours, selpercatinib and pralsetinib for RET + tumours, and crizotinib, alectinib and lorlatinib for ALK + tumours. Such a personalized approach increases clinical benefit whilst minimizing adverse events. Future studies should focus on the combination of tyrosine kinase inhibitors and immune-checkpoint inhibitors; currently, there is no strong evidence that redifferentiation strategies add clinical benefit in terms of overall survival or progression-free survival."

Journal • Review • Oncology • Solid Tumor • Thyroid Gland Carcinoma • ALK • NTRK

Artificial intelligence-enabled early intracranial volumetric response predicts systemic progression-free survival in the phase III CROWN study. (PubMed, Neurooncol Adv) - P3 | "CROWN randomized patients to lorlatinib or crizotinib. Volumetric all-BMs ETR outperforming target-only mRECIST offers early prognostic information in advanced ALK-positive NSCLC. ClinicalTrials.gov identifier: NCT03052608."

Journal • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Tolerance and Efficacy of Targeted Therapies After Immunotherapy for Advanced Non-Small Cell Lung Cancers Harboring Oncogenic Alterations: The GFPC-TOXIMAD Study. (PubMed, Curr Oncol) - "According to this analysis, sequential ICI-targeted therapy use for advanced NSCLC appeared to be associated with more grade 3-5 AEs."

IO biomarker • Journal • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • MET

Crizotinib versus observation or placebo for surgically resected early-stage ALK-positive non-small-cell lung cancer (Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E4512): a phase 3 trial. (PubMed, Lancet Respir Med) - P3 | "Adjuvant crizotinib does not prolong DFS in patients with surgically resected ALK-positive NSCLC. These findings suggest that crizotinib should not be recommended as an adjuvant therapy for patients with resected ALK-positive NSCLC."

Journal • P3 data • Cardiovascular • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Pulmonary Disease • Solid Tumor • ALK

Severe Immune-Related Adverse Events Associated with Durable Antitumor Responses Following Immune Checkpoint Inhibitor Therapy: Two Case Reports. (PubMed, Cancer Manag Res) - "Case one involved a patient with heavily pretreated Luminal B1 advanced breast cancer who developed Grade 3 immune-related arrhythmia and heart failure following treatment with Toripalimab combined with chemotherapy. Case two involved a patient with ROS1-fusion advanced lung adenocarcinoma who, after developing resistance to Crizotinib, received chemotherapy and Tislelizumab, leading to Grade 3 immune-related hypopituitarism, adrenal insufficiency, and cutaneous toxicity...However, the association between irAEs and efficacy is not straightforward, as the type and severity of irAEs and the use of immunosuppressive intervention all influence the ultimate clinical benefit. In the absence of reliable predictive biomarkers, clinical decisions should not equate irAEs directly with efficacy markers; rather, the benefits and risks of immune activation should be carefully weighed."

Adverse events • Checkpoint inhibition • IO biomarker • Journal • Breast Cancer • Cardiovascular • Congestive Heart Failure • Endocrine Disorders • Heart Failure • Lung Adenocarcinoma • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • ROS1

Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial) (clinicaltrials.gov) - P=N/A | N=7458 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2026 ➔ Dec 2025

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CTLA4 • PD-1 • PD-L1

Deulorlatinib (TGRX‑326) vs crizotinib in TKI-naive advanced ALK+ NSCLC: a phase 3 study (ESMO 2026) - No abstract available

Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Patient-reported outcomes from the randomized phase 3 CROWN study of first-line lorlatinib versus crizotinib in advanced ALK-positive non-small cell lung cancer. (PubMed, Lung Cancer) - "Patients receiving first-line lorlatinib or crizotinib showed improvements and delayed deterioration in QoL, functioning, and several symptoms. Alongside the previously reported significantly longer progression-free survival and higher intracranial response rates for lorlatinib versus crizotinib, these data further support the use of lorlatinib over crizotinib in patients with advanced ALK-positive NSCLC with/without baseline brain metastases and provide evidence of several QoL improvements with lorlatinib when used in the first-line setting."

Journal • P3 data • Patient reported outcomes • Anorexia • CNS Disorders • Constipation • Cough • Fatigue • Gastroenterology • Gastrointestinal Disorder • Immunology • Insomnia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Respiratory Diseases • Sleep Disorder • Solid Tumor • ALK

Targeting MET and mTOR Synergistically Overcomes Adaptive Resistance in Glioblastoma. (PubMed, Int J Mol Sci) - "Combining crizotinib with the mTOR inhibitor everolimus effectively suppressed mTOR activity, reduced cell viability, and induced mitochondrial alterations, apoptosis, and necroptosis. These effects were achieved without significant weight loss, supporting tolerability of the treatment regimen. Our findings identify the BNIP3-mTOR axis as a critical mediator of resistance to MET inhibition and demonstrate that combined inhibition of MET and mTOR exhibits significant synergy against GBM."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Study of Adjuvant Darovasertib and Crizotinib in Participants With Primary Non-metastatic Uveal Melanoma (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: IDEAYA Biosciences

New P3 trial • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Post Hoc Analysis of Lorlatinib Intracranial Efficacy and Safety in Patients With ALK-Positive Advanced Non-Small-Cell Lung Cancer From the Phase III CROWN Study. (PubMed, J Clin Oncol) - "First-line lorlatinib improved PFS outcomes and reduced CNS progression versus crizotinib in patients with advanced ALK-positive non-small-cell lung cancer with or without brain metastases at baseline. Half of all CNS AEs resolved without intervention or with lorlatinib dose modification."

Journal • P3 data • Retrospective data • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

A post-hoc analysis of the CROWN study in ALK+ NSCLC using AI to predict progression-free survival based on early response (ESMO 2025) - P3 | "Methods The study analyzed 249 evaluable pts treated with lorlatinib (LOR) or crizotinib (CRZ): 70 pts with baseline (BL) brain metastases (BMs) and 179 without. Conclusions AI lesion-level response at FU1 significantly predicted PFS in ALK+ NSCLC. Early BM response and lung radiomics enabled outcome estimation beyond RECIST, showing potential as early prognosticators in trials and practice."

Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Efficacy of alectinib for ALK-positive NSCLC according to tumor burden and body mass index: A pooled analysis of the randomized phase III trials ALEX and J-ALEX. (PubMed, Eur J Cancer) - P3 | "Tumor burden was prognostic and predictive in ALK-positive NSCLC. Treatment intensification may benefit patients with high tumor burden."

Journal • P3 data • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Iruplinalkib (WX-0593) versus crizotinib in ALK TKI-naïve locally advanced or metastatic ALK-positive non-small cell lung cancer: interim analysis of a randomized, open-label, phase III study (INSPIRE). (PubMed, J Thorac Oncol) - P3 | "Iruplinalkib demonstrated significantly improved PFS and improved intracranial antitumor activity versus crizotinib. Iruplinalkib may be a new treatment option for patients with advanced ALK positive and ALK TKI-naïve NSCLC."

Journal • Metastases • P3 data • P3 data: top line • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Real-World Clinical Outcomes, Healthcare Utilization, and Costs of ALK TKIs in Patients With ALK+ NSCLC: A Claims Analysis (IASLC-WCLC 2026) - "Patients were categorized by the TKI generation: first-generation (crizotinib) or second/third generation (ceritinib, alectinib, brigatinib, lorlatinib). The favorable 1-year OS rate of 97.8% and a manageable adverse event profile further support the real-world effectiveness and value of modern ALK TKIs. These findings underscore the importance of comprehensive payer-level cost-consequence analyses to characterize the full economic and clinical value of targeted therapies in ALK+ NSCLC."

Clinical • Clinical data • HEOR • Real-world • Real-world evidence • Febrile Neutropenia • Interstitial Lung Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ALK

Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial. (PubMed, JAMA Oncol) - P3 | "Ensartinib represents a new first-line option for patients with ALK-positive NSCLC. ClinicalTrials.gov Identifier: NCT02767804."

Clinical • Journal • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK