Xalkori (crizotinib) / Pfizer - LARVOL DELTA

Postoperative recurrence of ROS1-rearranged lung adenocarcinoma: A case series. (PubMed, Thorac Cardiovasc Surg) - "Crizotinib showed limited efficacy with a median progression-free survival of 3.5 months. These findings highlight indolent disease behavior but limited TKI benefit, supporting the need for adjuvant trials."

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

Development of ALK-directed TCR-T cells with potent and specific anti-tumor activity against ALK-positive anaplastic large cell lymphoma (ASH 2025) - "The ALKtyrosine kinase inhibitor (TKI) crizotinib is approved for use in children and young adults with relapsed orrefractory disease... We identified ALK-specific TCRs that recognize an ALK peptide displayed by HLA-B*07:02and proved their specificity and potent in vitro anti-tumor activity. Ongoing studies are investigating thetherapeutic potential of ALK TCR-T cells in vivo using relevant ALK-positive ALCL mouse models. Resultson these in vivo studies will be reported at the meeting."

IO biomarker • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • ALK • CD4 • CD8 • HLA-B • IFNG • NPM1 • TNFRSF9

Underexplored mutations in plasma cell myeloma (ASH 2025) - "Many FDA-approved therapies exist in other cancers (such as sotorasib, selumetinib,vemurafenib, enasidenib, midostaurin, ruxolitinib, crizotinib, erlotinib), though these remain largelyunexplored in PCM. CHIP mutation burden in MM / PCM was 40%, Our analysis identified several potentially targetablemutations in pts with PCM, including KRAS, NRAS, BRAF, IDH2, FLT3, JAK2, ALK, and EGFR. Clonalhematopoiesis (CH/CHIP) mutations, such as DNMT3A, TET2, ASXL1, and SRSF2, were also observed.Although the lineage origin of several targetable mutations remains unclear, the likely high plasma cellburden in PCM cases suggests that many may originate within the malignant plasma cell clone. Thishypothesis warrants systematic investigation in future studies."

Tumor mutational burden • Hematological Malignancies • Multiple Myeloma • ALK • ASXL1 • BCOR • BRAF • CALR • CREBBP • CSF3R • DNMT3A • EGFR • FLT3 • GNAS • IDH2 • JAK2 • KRAS • NRAS • PHF6 • PPM1D • PRPF8 • SRSF2 • SUZ12 • TET2 • TMB • TP53

Pharmacologic overactivation of ALK activity by PTPN2/PTPN1 inhibition induces a combination of tumor-intrinsic oncogenic stress and immune responses to promote tumor eradication in ALK-positive lymphoma (ASH 2025) - P1 | "We tested in vitro and in vivo in mouse models the inhibitor ABBV-CLS-484 whichis currently evaluated in a Phase 1 trial in subjects with locally advanced or metastatic tumors(NCT04777994).Materials and MethodsIn vitro treatment with the ALK inhibitor crizotinib (TKI) or the PTPN2/PTPN1 phosphatase inhibitor ABBV-CLS-484 (AC484) with increasing concentrations at various time points was performed on ALK+ and ALK-ALCL cell lines. Remarkably, AC484 amplifies ALK signaling resulting in oncogenic stress and anti-tumoractivity selectively in ALK+ ALCL cells, even if resistant to ALK TKI. The anti-tumor activity of AC484 wasdemonstrated also in vivo, promoting the complete eradication of ALK+ lymphoma in immunocompetentbut not in immunodeficient mice, demonstrating the importance of inducing a more potent anti-ALKimmune response to achieve cure."

Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALK • CD8 • NPM1 • PTPN1 • PTPN2

Crizotinib plus chemotherapy versus crizotinib alone in advanced non-small cell lung cancer with ALK rearrangement (ESMO Asia 2025) - "Background: Lorlatinib, a 3rd-gen ALK inhibitor (ALKi), & 2nd-gen ALK inhibitors are recommended for the treatment of advanced ALK-rearranged NSCLC...Participants were randomized 1:1 to receive Crizotinib 250 mg BD or Crizotinib 250 mg BD + Pemetrexed 500mg/m2 + Carboplatin AUC 5 q3w; followed by Crizotinib + Pemetrexed... The combination of crizotinib + chemotherapy did not improve the DCR and PFS in patients with ALK re-arranged NSCLC."

Late-breaking abstract • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK

Role of Blood-Based Next-Generation Sequencing in Guiding Targeted Therapy for Non-small cell Lung Cancer in the Absence of Histopathological Diagnosis, a case report (ESMO Asia 2025) - "After multidisciplinary consultation, crizotinib 250 mg twice daily was initiated; hemoptysis abated within seven days... This case delineates two propositions: when cancer tissue is unobtainable, blood-based NGS detection, integrated with clinical–radiologic–laboratory phenotype, suffices as an exceptional diagnostic modality. Moreover, no data yet report on ROS1 exon 6 c.G500A to targeted therapy efficacy, deliberate investigation of such point mutations may broaden therapeutically addressable populations. Keywords: blood-based NGS; Lung Cancer; ROS-1; Pathological Diagnosis"

Biomarker • Case report • Clinical • Next-generation sequencing • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

A phase II, multi-center, open-label, single-arm study to evaluate the efficacy and Safety of lorlatinib in TKI naïve, advanced ROS1-positive non-small cell lung cancer patients with brain metastases (ESMO Asia 2025) - P2 | "While ROS1-tyrosine kinase inhibitors (TKIs) (e.g., crizotinib, entrectinib, repotrectinib) improve outcomes in ROS1-positive NSCLC, intracranial efficacy remains suboptimal, representing a critical unmet need. At present, no efficacy or safety results are available. Data collection for safety and efficacy endpoints is ongoing."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Genomic landscape of advanced non-small cell lung cancer (aNSCLC) using circulating tumor DNA (ctDNA) next generation sequencing (NGS): A single-center analysis in Taiwan (TW) (ESMO Asia 2025) - "2021, pt was initiated on Crizotinib therapy, and achieved partial response (PR)... In this single-center study of aNSCLC pts in TW, ctDNA NGS identified genomic alts in more than three-quarters of cases with a swift mTAT, supporting its use to guide treatment decisions."

Biomarker • Circulating tumor DNA • Clinical • Metastases • Next-generation sequencing • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS • PIK3CA • ROS1 • TP53

ALK -positive lung cancer in India: Real world barriers to precision oncology (ESMO Asia 2025) - "Concomitant mutation with TP53 was seen in 5 patients and with EGFR in 3 patients.In the first line 29(48%) patients received crizotinib,15(25%), ceritinib, 4(6%) alectinib, 6(10%) chemotherapy, 3(5%) lorlatinib. ALK positivity was seen in 10% of NSCLC patients. Survival rates of ALK positive lung cancer has improved significantly with the advent of targeted therapy. CNS progression on first generation TKI remains a challenge as most of the patients are deprived of newer generation TKI due to financial constraints."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • TP53

A multi-centre, real-world study of treatment patterns and outcomes in Anaplastic Lymphoma Kinase (ALK)-rearranged non-small cell lung cancer: The Singapore experience (ESMO Asia 2025) - "ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, ceritinib, alectinib, brigatinib and lorlatinib are among the therapeutic options. ALK TKIs are effective in treating ALK-rearranged NSCLC in the real world setting, mirroring results from randomised trials. Factors to consider in deciding 1L TKI include overall and BM efficacy and toxicities."

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

Subgroup analysis of japanese patients in the phase II study of taletrectinib in patients with ROS1+ NSCLC: The global TRUST-II study (ESMO Asia 2025) - P2 | "In 10 TKI-pretreated pts (7 crizotinib, 3 entrectinib), cORR 70% (95% CI: 34.8, 93.3), IC-cORR 100% (95% CI: 29.2, 100; 3/3), and median DOR 19.4 months (95% CI: 2.8, NE). Taletrectinib continues to show high and durable overall responses, robust intracranial activity, in Japanese ROS1+ NSCLC both in TKI-naïve and -pretreated in the TRUST-II study. The safety profile, including low neurologic adverse events, was consistent with entire cohort, supporting its efficacy and tolerability in this population."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Drug utilisation evaluation of oral anticancer therapy in a south indian cancer centre (ESMO Asia 2025) - "Among targeted therapies, Gefitinib, Osimertinib, Crizotinib, Afatinib, Lorlatinib, and Nilotinib demonstrated consumption of 30 DDDs per patient over 30 days. Lower consumptions were observed with Lenvatinib and Cabozantinib with 13.3 DDDs and 11.25 DDDs per patient respectively. In the hormonal therapy group, Letrozole, Tamoxifen, Bicalutamide, Anastrozole, Enzalutamide, and Exemestane were all prescribed in line with WHO standards (30 DDDs per patient), whereas Abiraterone exhibited lower consumption of 15 DDDs per patient. Prescribing patterns and consumption metrics were largely consistent with WHO criteria, indicating rational oral anticancer drug use. Prescribing patterns and consumption metrics were largely consistent with WHO criteria, indicating rational oral anticancer drug use. Dose deviations occurred, though reasons were unclear and may relate to adverse effects, indication-specific or patient factors, or economic constraints. Further research is warranted..."

Oncology • Oral Cancer

Functional Precision Medicine In Glioblastoma: Advancing Drug Screening With Patient-Derived 3D Cultures And Advanced Imaging Analyses (SNO 2025) - "Resistance to the trimodal standard—resection, radiotherapy, and temozolomide—demands novel, patient-tailored strategies...(3) Drug efficacy proved patient-specific: in 3-D, imatinib was most potent in Patients 1, 3, 5, 6; crizotinib in Patients 2; osimertinib in Patients 3 and 5; and pazopanib in Patients 4 and 7... Integrating mechanistic assays with patient-matched organoids unmasks actionable kinase dependencies and eliminates misleading 2-D signals. This scalable workflow refines preclinical drug ranking, supports adaptive trial enrollment, and could anchor statewide precision-oncology programs aimed at extending survival for patients with GBM and related gliomas."

Metastases • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Solid Tumor • ANXA5

Alectinib versus crizotinib as the first-line treatment in patients with advanced ALK-positive non-small cell lung cancer: a Chinese real-world cohort study. (PubMed, Transl Lung Cancer Res) - "While the presence of bone, liver, and adrenal metastasis were independent risk factors for OS. Alectinib is recommended over crizotinib in the treatment of patients with ALK-positive NSCLC."

Journal • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Next-Generation Targeted Therapy: The Evolving Role of Taletrectinib in Fusion-Positive Malignancies. (PubMed, Zhongguo Ying Yong Sheng Li Xue Za Zhi) - "First-generation tyrosine kinase inhibitors (TKIs) such as crizotinib displayed significant early reactions but faced challenges due to restricted central nervous system (CNS) penetration and mutation resistance, while entrectinib and larotrectinib expanded treatment options but also experienced resistance...Safety data shows an acceptable toxicity profile, mainly featuring gastrointestinal and hepatic adverse effects, with fewer neurocognitive side effects compared to lorlatinib...Current trials and regulatory activities in China, the U.S., and other locations demonstrate taletrectinib's growing clinical significance. Taletrectinib's well-rounded pharmacological attributes of systemic action, intracranial effectiveness, resistance range, and tolerability render it an intriguing enhancement to the framework of precision oncology."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK • ROS1

Evolving Therapeutic Landscape of ROS1-Positive Non-Small Cell Lung Cancer: An Updated Review. (PubMed, Curr Oncol) - "Crizotinib first demonstrated substantial clinical benefit, but its limitations, including poor central nervous system (CNS) penetration and acquired resistance, highlighted the need for next-generation inhibitors. Several agents have since been developed, including entrectinib, lorlatinib, repotrectinib, taletrectinib, and zidesamtinib, each offering improved intracranial (IC) activity and efficacy against resistance mutations, notably ROS1^G2032R. Despite these advances, optimal sequencing strategies remain undefined, and resistance ultimately emerges in most patients. This review provides an updated overview of ROS1 biology, diagnostic approaches, clinical outcomes with currently available TKIs, mechanisms of resistance, and ongoing challenges, emphasizing the rapidly evolving therapeutic landscape."

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

Rare but not forgotten: Therapeutic advancements for rare childhood cancers. (PubMed, Mol Ther Oncol) - "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."

Journal • Review • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Pediatrics • Sarcoma • Solid Tumor • NTRK • SSTR

Neoadjuvant Alectinib in a Patient With Anaplastic Lymphoma Kinase (ALK)-Mutant Stage III Lung Adenocarcinoma: A Case Report. (PubMed, Cureus) - "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."

IO biomarker • Journal • Immunology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4

Lorlatinib in Tyrosine Kinase Inhibitor-Naive Advanced ROS1-Positive Non-Small Cell Lung Cancer: A Phase 2 Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. In this nonrandomized clinical trial, lorlatinib demonstrated durable efficacy and manageable safety in TKI-naive advanced ROS1-positive NSCLC, supporting the potential for using lorlatinib in earlier treatment settings. ClinicalTrials.gov Identifier: NCT03612154."

Clinical • Journal • P2 data • Dyslipidemia • Hypertriglyceridemia • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3) (clinicaltrials.gov) - P3 | N=190 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: Mar 2027 ➔ Mar 2026

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Complete response in ROS1-Rearranged lung cancer under crizotinib: A case report and literature review [WITHDRAWN] (ESMO Asia 2025) - No abstract available

Case report • Clinical • Review • Lung Cancer • Oncology • Solid Tumor • ROS1

Combinatorial Treatment Options for Highly Resistant Compound Mutations in the Kinase Domain of the BCR: : ABL1 Fusion Gene (ASH 2023) - "The cells pre-tested in this way were exposed in vitro to different concentrations of various drugs including ponatinib combined with a number of other agents such as asciminib, hydroxyurea, palbociclib, venetoclax, ibrutinib, vodobatinib, and crizotinib...Overall, combinatorial treatment of BCR: : ABL1 CMs indicated that relatively low concentrations of the drugs used are capable of effectively inhibiting in vitro survival of mutant cells in most instances, which is important with regard to the expected toxicity of combinatorial treatment approaches. Since our earlier data indicated a good correlation between in vitro test results and clinical responses, our observations may serve as a basis for novel treatment options in patients with Ph +leukemias displaying challenging BCR: : ABL1 KD-mutations."

Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

A Rollover Study of Alectinib in Patients With Anaplastic Lymphoma Kinase (ALK)-Positive or Rearranged During Transfection (RET)-Positive Cancer (clinicaltrials.gov) - P3 | N=200 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2025 ➔ May 2026 | Trial primary completion date: Oct 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Oncology

OFF-LABEL TREATMENT AND ULTRARARE SARCOMAS - SINGLE INSTITUTION REPORT (CTOS 2025) - "Off-label therapies included: atezolizumab for alveolar ASPS (n=11); ivosidenib and pazopanib for chondrosarcoma (n=11; 2 and 9); imatinib and pembrolizumab for chordoma (n=14; 5 and 9); sirolimus for epithelioid hemangioendothelioma EHE (n=8); cabozantinib for Ewing sarcoma ES (n=11); crizotinib and alectinib for inflammatory myofibroblastic tumor IMT (n=1 and 2); sorafenib for osteosarcoma (n=7); pembrolizumab for sclerosing epithelioid sarcoma SEF (n=2)... Off-label treatments can improve outcomes in ultrarare sarcoma subtypes: ASPS (atezolizumab), EHE (sirolimus), SEF (pembrolizumab). 3-year survival rates and median EFS surpass historical data. Younger patients show more aggressive disease with shorter EFS."

Clinical • Chordoma • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Health-related quality of life among anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients treated with first- and next-generation ALK tyrosine kinase inhibitors (TKIs): a systematic review and meta-analysis. (PubMed, Qual Life Res) - "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."

HEOR • Journal • Retrospective data • Review • Anorexia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK