Xalkori (crizotinib) / Pfizer - LARVOL DELTA

Molecularly-informed prediction of treatment efficacy in the GENIE BPC NSCLC cohort using computational reasoning (AACR 2026) - "Here, we extend this analysis to the GENIE BPC NSCLC cohort to assess the broader clinical validity of DDA. From the GENIE BPC NSCLC cohort data available on Synapse, we included 1,078 patients with a single-sample genomic profile, available primary treatment data and survival outcomes (total 2,103 treatment lines, therapies included: afatinib, erlotinib, osimertinib, crizotinib, nivolumab, pembrolizumab, atezolizumab, bevacizumab+chemo, ramucirumab+chemo; and chemotherapy alone). Across a large, real-world NSCLC cohort, DDA effectively distinguished therapies with higher clinical efficacy based on the full molecular profile of each patient. These results reinforce the potential of DDA to enhance personalized treatment selection based on NGS diagnostics in precision oncology."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Case Report: Pregnant ROS1+ lung cancer patient treated with crizotinib - Impact on infancy. (PubMed, Front Oncol) - "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."

Journal • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

First-line lorlatinib versus crizotinib in Asian patients with advanced ALK-positive NSCLC: 5-year outcomes from the CROWN study. (PubMed, J Thorac Oncol) - P3 | "After 5 years of follow-up, lorlatinib efficacy and safety in the Asian subgroup of CROWN continue to be consistent with those in the overall population, with PFS remaining unreached with lorlatinib."

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

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

Longitudinal methylation- vs genomic-based circulating tumor DNA molecular response analysis in patients with ALK+ advanced non-small cell lung cancer treated with lorlatinib in the CROWN study (ESMO 2025) - P3 | "Earlier analysis from CROWN showed that C2D1 circulating tumor DNA (ctDNA) reduction based on genomic variants predicted better outcomes in pts treated with lorlatinib but did not predict crizotinib response; however, ctDNA change was not quantifiable in many pts due to low shedding. Conclusions This analysis from the CROWN study showed that methylation-based TF was more sensitive in detecting ctDNA than genomic methods and can provide informative results in more pts; furthermore, methylation TF can stratify PFS in pts with undetectable ctDNA by genomics. Comparison of TF change at C2D1 and C7D1 indicates that MR at C7D1 is a better predictor of PFS than at C2D1 in pts treated with lorlatinib and adds to the body of literature supporting ctDNA as an early endpoint."

Circulating tumor DNA • Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Acquired EGFR L858R mutation following ALK-TKI resistance in lung adenocarcinoma: a case report. (PubMed, Front Oncol) - "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."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Case Report: TPR-ALK fusion-positive inflammatory myofibroblastic tumour treated with sequential ALK inhibitors. (PubMed, Front Oncol) - "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."

Journal • Oncology • ALK

Network-based discovery of tumor-checkpoint inverter drugs targeting pancreatic ductal adenocarcinoma cell states and macrophage reprogramming (AACR 2026) - "Cross-model validation identified state-specific candidate drugs, including Leuprolide, Vinblastine, and Mercaptopurine for GLS; Vindesine, Gossypol, and Binimetinib for MOS; and AT9283, Crizotinib, and Afatinib for PLS. Predicted MR-inversion scores correlated with experimental dose-response profiles in cell lines selected via OncoMatch.Together, these results establish a mechanistic link between tumor-intrinsic transcriptional states and macrophage immunosuppression, while identifying mutation-agnostic, state-specific drugs capable of reprogramming both tumor and immune compartments. This work provides a generalizable framework for network-based drug repurposing to overcome transcriptional plasticity and immune resistance in PDAC."

Oncology • Pancreatic Ductal Adenocarcinoma • APOE

Final Analysis of Brighstar: LCT With Brigatinib in Tyrosine Kinase Inhibitor-Naïve ALK-Rearranged Metastatic NSCLC (IASLC-WCLC 2025) - P1, P3 | "Individual patient data from a phase 3 trial of brigatinib vs crizotinib (ALTA-1L, NCT02737501) were retrospectively compared...One patient with grade 3 pneumonitis successfully transitioned to full-dose alectinib after resolution with corticosteroids...Conclusions : Brigatinib with LCT is safe in patients with ALK-rearranged advanced NSCLC and yielded promising results when compared to historical outcomes from brigatinib alone. Patients who received comprehensive LCT had superior outcomes, and baseline ctDNA status and radiological volumetric measurements may serve as prognostic biomarkers for treatment response."

Metastases • Anemia • Endocrine Disorders • Gastrointestinal Disorder • Hematological Disorders • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Pneumonia • Renal Disease • Solid Tumor • ALK

Efficacy of lorlatinib after failure of a first-line ROS1 tyrosine kinase inhibitor (ROS1 TKI) in patients (pts) with advanced ROS1-positive non-small cell lung cancer (ROS1+ NSCLC) (IFCT-2003 ALBATROS) (ESMO 2025) - P2 | "Background Current ESMO guidelines recommend ROS1 TKIs crizotinib and entrectinib as preferred first-line treatments for advanced ROS1 + NSCLC. Conclusions In this phase II trial, lorlatinib demonstrated robust clinical activity in ROS1+ NSCLC pts who received one line of ROS1+ TKI, mostly crizotinib. Lorlatinib activity according to baseline molecular profile including resistance mutation to crizotinib will be presented."

Clinical • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

EAY131-C2: Testing Crizotinib as Potentially Targeted Treatment in Cancers With MET Exon 14 Deletion Genetic Changes (MATCH - Subprotocol C2) (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=35 ➔ 20 | Trial completion date: Feb 2026 ➔ Dec 2026

Enrollment change • Trial completion date • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor

Crizotinib-Induced Lichenoid Drug Eruption Presenting as a Lower-Lip Ulcer (AAD 2026) - No abstract available

Lichen Planus

Sequential met inhibition from crizotinib to capmatinib in a patient with advanced met-amplified intrahepatic cholangiocarcinoma:a case report (APASL 2026) - No abstract available

Case report • Clinical • Metastases • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Final overall survival (OS) and safety analysis of the phase III ALEX study of alectinib vs crizotinib in patients with previously untreated, advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC) (ESMO 2025) - P3 | "Safety data were in line with the known safety profile of alectinib. These data continue to support 1L alectinib as a standard of care in pts with advanced ALK + NSCLC."

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

EAY131-C1: Testing Crizotinib as Potentially Targeted Treatment in Cancers With MET Genetic Changes (MATCH - Subprotocol C1) (clinicaltrials.gov) - P2 | N=44 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Feb 2026 ➔ Dec 2026

Trial completion date • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor

Intragenic fusion architecture dictates resistance: UGT1A1 links CD74-ROS1 breakpoint heterogeneity to TKI response (ELCC 2026) - "The molecular mechanism underlying this variant-specific intrinsic resistance remains completely unknown, representing a major gap in knowledge that impedes personalized therapeutic strategies.Methods To elucidate the mechanism, we established isogenic NSCLC cell models expressing CR-L or CR-S and systematically evaluated their in vitro sensitivity (IC50) to multiple ROS1 TKIs (crizotinib, entrectinib, and lorlatinib). We identify UGT1A1-mediated metabolism as a novel, variant-specific resistance mechanism in CR-L NSCLC-a new paradigm distinct from acquired mutations. Our findings nominate UGT1A1 as a predictive biomarker and establish a directly translatable combinatorial strategy (atazanavir + lorlatinib) to overcome this primary resistance."

Heterogeneity • Lung Cancer • Non Small Cell Lung Cancer • CD74 • ROS1 • UGT1A1

Real-world safety of ALK inhibitors in non-small cell lung cancer patients: A FAERS disproportionality analysis (ELCC 2026) - "In the cardiac cluster, crizotinib showed marked bradycardia (ROR 12.52, CI 9.57–16.37), with lower but similar signals for alectinib. Gastrointestinal signals were most frequent with ceritinib, while pulmonary disproportionality was observed primarily with lorlatinib, brigatinib, and crizotinib.Conclusions Relative to other NSCLC therapies, ALKis are associated with higher reporting signals across the eye, nervous system, cardiac, musculoskeletal, gastrointestinal, and pulmonary adverse event clusters, with agent-specific disproportionalities being noted. The findings are consistent with ALKi's known safety profiles, emphasizing the importance of corroborating clinical trials with real-world data and the value of pharmacovigilance findings in treatment selection."

Clinical • Real-world • Real-world evidence • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Real-world clinical, molecular, treatment patterns and outcomes of rare mutations in lung cancer from community oncology centres in Western India (ELCC 2026) - "Among mutated cases receiving targeted therapy, MET alterations (n=12) were treated with crizotinib, capmatinib & tepotinib (each n=4); KRAS co-mutations (n=13) mainly received bevacizumab-based regimens (n=6), followed by trametinib (n=2) & Nintedanib (n=1); BRAF-altered tumors (n=7) were mainly treated with chemotherapy & few were targeted with dabrafenib + trametinib (n=3); RET mutations (n=8) received cabozantinib & selpercatinib (each n=3); HER2 alterations (n=21) were mainly managed with trastuzumab -based regimens (n=13). With a median follow-up of 16.3 months, median overall survival (mOS)for the cohort was 13.9 mo(95% CI 10.6–17.1; mOS for single mutation was 15.9 mo vs 12.3 mo for co-mutations (p=0.637).mOS by mutation subtype was 14.3 mo (95% CI 0.0–68.6) for MET, 35.0 mo (95% CI NA–NA) for RET, 13.7 mo (95% CI 8.7–18.7) for BRAF, 10.3 mo (95% CI 2.4–18.2) for HER2, while KRAS/TP53 mutations had mOS of 13.1mo (95% CI 9.4–16.8).Conclusions This..."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • HER-2 • KRAS • MET • PD-L1 • RET • ROS1 • TP53

Updated Efficacy and Safety of Taletrectinib in Patients With ROS1+ Non-Small Cell Lung Cancer: The Global TRUST-II Study (IASLC-WCLC 2025) - P2, P3 | "Enrollment in TRUST-II is ongoing. Efficacy and safety of taletrectinib will be directly compared with crizotinib in an ongoing randomized head-to-head phase 3 trial in TKI-naive patients with locally advanced or metastatic ROS1 + NSCLC (NCT06564324)."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

DAR-UM-2: IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma (clinicaltrials.gov) - P2/3 | N=420 | Active, not recruiting | Sponsor: IDEAYA Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

ALK-specific TCR-T cells showed potent and specific activity in ALK-positive anaplastic large cell lymphoma (AACR 2026) - "We demonstrated that ALK.TCR-T show specific and potent anti-tumor activity against multiple ALK+ ALCL models both in vitro and in vivo. The combination of ALK.TCR-T and crizotinib further potentiate the ability of ALK.TCR-T to control tumor growth and extend the survival of mice. These results lay the basis for developing a novel immunotherapy strategy for patients with ALK+ ALCL."

Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • ALK • HLA-B • NPM1

Taletrectinib, a next generation selective ROS1 inhibitor, demonstrates a differentiated profile in ROS1 fusion models (AACR 2026) - "FDA-approved tyrosine kinase inhibitors (TKI) for ROS1 fusion positive NSCLC include crizotinib, entrectinib, repotrectinib, and more recently, taletrectinib. Taletrectinib treatment also induced tumor regressions in several in vivo ROS1 fusion models, regardless of the fusion partner. In summary, our nonclinical data demonstrate that, at clinically relevant concentrations, taletrectinib exhibits activity in ROS1 wild-type and mutant-driven cancers and has a distinct profile that addresses the unmet needs of ROS1-positive NSCLC patients."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK2

Quantifying evolutionary dynamics and tumor heterogeneity in oncogene-addicted advanced non-small cell lung cancer (AACR 2026) - "In pt992, 3 ALK double-mutant subclones shared an original mutation F1193Y, and independently acquired secondary hits G1269A, E1210K, and G1210R, driving differential resistance to Crizotinib and Lorlatinib. RNA-seq immune deconvolution via CIBERSORT showed variable immune cell infiltration patterns without correlation to clinical outcome. These results demonstrate that TKIs drive clonal diversification and evolution of resistance in oncogene-addicted NSCLC, and offer a quantitative framework for lineage-informed therapeutic strategies."

Heterogeneity • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Integrative pathway analysis of I-SPY2 HER2+ breast cancers reveals drug-repurposing opportunities (AACR 2026) - "Growth-factor/RTK bypass (PI3K/AKT) and DNA repair & oxidative stress defense were strongly upregulated in non-responders within BP-HER2, revealing actionable nodes involving PI3K/AKT (alpelisib, capivasertib), IGF1R (linsitinib), MET (crizotinib, capmatinib), and DNA repair (PARP inhibitors). Notably, metabolic rewiring and lipid homeostasis—targetable by vismodegib and sonidegib—were upregulated in non-responders across both BP subtypes, reflecting a shared metabolic vulnerability. Luminal biology-linked transcriptional programs may persist within the HER2+ BP-HER2 subtype and contribute to resistance... Luminal biology-linked transcriptional programs may persist within the HER2+ BP-HER2 subtype and contribute to resistance. BP-HER2 non-responders exhibit coordinated activation of RTK-bypass and DNA repair pathways, exposing therapeutic vulnerabilities targetable by existing agents. Furthermore, targeting lipid metabolic reprogramming alongside anti-HER2 therapy..."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Use of ALK inhibitors in patients with non-lung malignancies bearing ALK alteration prolongs treatment duration (AACR 2026) - "ALK inhibitors were administered as third-line or later in 52% of patients, with alectinib being the most common (52%), followed by crizotinib (36%). Among 15 patients on ALK inhibitors with imaging, 7 had partial responses, 4 had stable disease, and 1 achieved a complete response.ConclusionALK inhibitors improved clinical outcomes in comparison with prior therapies across several malignancies. This supports the rationale for its agnostic use for tumors where clinical trials are not feasible."

Clinical • Gastric Adenocarcinoma • Genito-urinary Cancer • Lung Cancer • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Sarcoma • Solid Tumor