Lorbrena (lorlatinib) / Pfizer, CStone Pharma - LARVOL DELTA

The immunomodulatory effects of IRF3/7 transcription factors and IL10 in ALK+ anaplastic large cell lymphoma (ALCL) (ASH 2025) - "Ceritinib and Lorlatinib were used as a next generation ALK inhibitors in vitro. Our findings provide evidence that the IRF3 and IRF7 transcription factors are dependent onfunctional cGAS-STING pathway and substantially contribute to anti-tumor immune responses in ALK+ALCL. As NPM/ALK-STAT3-IL10 axis suppresses IRF3/7 - mediated immunomodulatory effects, targetingthis oncogenic axis combined with stimulation of the cGAS-STING pathway may represent an efficienttherapeutic strategy for patients with refractory or relapsing ALK+ ALCL."

Immunomodulating • Lymphoma • Non-Hodgkin’s Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • BSG • CCL2 • CXCL9 • IFNB1 • IGFBP3 • IL10 • IL17A • IL6 • IRF3 • IRF7

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

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

Observational study to investigate the safety and effectiveness of first-line lorlatinib in patients with ALK gene–rearranged unresectable advanced/recurrent non-small cell lung cancer in real-world clinical settings in Japan (ESMO Asia 2025) - "This is the first study to report RW data for 1L lorlatinib in ALK+ aNSCLC in clinical practice in Japan. These interim results of the ROYAL study indicate an acceptable degree of tolerability of 1L lorlatinib in the RW setting. However, longer follow-up is needed to assess its long-term safety and effectiveness."

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

Poor efficacy of first-line alectinib or lorlatinib in advanced ALK-rearranged NSCLC with MET overexpression (ESMO Asia 2025) - "First-line alectinib or lorlatinib demonstrated poor efficacy in advanced ALK-rearranged NSCLC with concurrent MET overexpression. Further investigations are warranted to elucidate the underlying mechanisms and identify potential therapeutic strategies."

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

Neoadjuvant lorlatinib with or without chemotherapy followed by surgery in resectable stage IB-IIIB ALK+ NSCLC: An open-label, randomized, phase II study (LORTAN) (ESMO Asia 2025) - P4 | "Exploration endpoint is potential mechanisms underlying disease persistence and potential resistance mechanism of neoadjuvant lorlatinib. Enrollment has begun in May 2025."

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

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

Increased Cardiovascular Risk With Lorlatinib in Patients With ALK-Mutated Lung Cancer: A Real-World Comparative Study. (PubMed, J Am Heart Assoc) - "These findings underscore the importance of routine cardiovascular monitoring, particularly in older patients and those with atrial arrhythmias."

Journal • Real-world evidence • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Lung Cancer • Myocardial Infarction • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

Real-world first-line outcomes of alectinib and brigatinib in anaplastic lymphoma kinase-positive non-small cell lung cancer: a nationwide South Korean cohort study using the health insurance review and assessment data. (PubMed, Transl Lung Cancer Res) - "Transition to lorlatinib was associated with extended survival in both groups, reflecting its use as a later-line therapy following resistance. Alectinib demonstrated superior disease control in terms of PFS. Further research is warranted to optimize treatment sequence strategies for ALK inhibitors."

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

Molecularly-guided phase 2 umbrella trial for children and young adults with newly-diagnosed high-grade glioma (HGG) including diffuse intrinsic pontine glioma (DIPG): CONNECT TarGeT (Targeted pediatric HGG therapy) trial in progress (WFNOS 2025) - P, P2 | "The following TarGeT treatment arms (most involving upfront radiotherapy), are open or soon to open, selected based on prevalence of targets in HGG/DIPG, relevant pre-clinical and clinical data, established pediatric safety data, and prioritizing combinations: (A) ribociclib and everolimus (target: cell cycle or PI3K//mTOR pathway alterations) [NCT05843253], (A-2) ribociclib and temozolomide (H3G34 mutation) (B) tovorafenib (MAPK pathway alterations), (D) olutasidenib and temozolomide (IDH1 mutation) [NCT06161974], (F) nivolumab and relatlimab (high tumor mutational burden, mismatch repair deficiency), (L) lorlatinib (+/- chemotherapy or radiation) (ROS1, ALK fusion). Development of additional treatment arms is underway, with possibility of incorporating new arms as supporting data allows."

Clinical • P2 data • Tumor mutational burden • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Pediatrics • Solid Tumor • ALK • IDH1 • ROS1 • TMB

Molecularly-guided phase 2 umbrella trial for children and young adults with newly-diagnosed high-grade glioma (HGG) including diffuse intrinsic pontine glioma (DIPG): CONNECT TarGeT (Targeted pediatric HGG therapy) trial in progress (SNO 2025) - P, P2 | "The following TarGeT treatment arms (most involving upfront radiotherapy), are open or soon to open, selected based on prevalence of targets in HGG/DIPG, relevant pre-clinical and clinical data, established pediatric safety data, and prioritizing combinations: (A) ribociclib and everolimus (target: cell cycle or PI3K//mTOR pathway alterations) [NCT05843253], (A-2) ribociclib and temozolomide (H3G34 mutation) (B) tovorafenib (MAPK pathway alterations), (D) olutasidenib and temozolomide (IDH1 mutation) [NCT06161974], (F) nivolumab and relatlimab (high tumor mutational burden, mismatch repair deficiency), (L) lorlatinib (+/- chemotherapy or radiation) (ROS1, ALK fusion). Development of additional treatment arms is underway, with possibility of incorporating new arms as supporting data allows."

Clinical • P2 data • Tumor mutational burden • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • High Grade Glioma • Pediatrics • Solid Tumor • ALK • IDH1 • ROS1 • TMB

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

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

Managing lorlatinib-induced weight gain through a structured exercise intervention in an ALK+ NSCLC patient: a case report. (PubMed, Front Oncol) - "Among the patient-reported outcomes, different domains of quality of life improved. This case may represent the backbone for further interventional studies aimed at determining the real efficacy of exercise intervention in preventing or controlling weight gain in this population."

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

Navigating Management of Spindle Cell/Sclerosing Rhabdomyosarcoma With FUS::TFCP2 Fusion in the Era of Targeted Therapy. (PubMed, J Pediatr Hematol Oncol) - "We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset."

Journal • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Spindle Cell Sarcoma • FUS • TFCP2

Long-Term Safety and Management of Adverse Events Associated With Lorlatinib in ALK-Positive Metastatic NSCLC: A Fictional Case Study. (PubMed, J Adv Pract Oncol) - P3 | "These results, along with the extended intracranial efficacy and consistent safety profile of long-term lorlatinib treatment, are unprecedented in patients with ALK-positive mNSCLC. This Grand Rounds article summarizes the efficacy, safety, and tolerability of lorlatinib after 5 years and includes a fictional patient case to demonstrate how advanced practice providers contribute to personalized patient care and the identification and management of adverse events."

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

A Real-world Study on the Incidence and Risk Factors of Neurocognitive Adverse Events of Lorlatinib in ALK+ Advanced NSCLC [WITHDRAWN] (ESMO Asia 2025) - No abstract available

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

Real-world experience with lorlatinib therapy in ALK-positive, pretreated non-small cell lung cancer patients in Russia [WITHDRAWN] (ESMO Asia 2025) - No abstract available

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

Fes tyrosine kinase as a novel immunotherapeutic target (ESMO-IO 2025) - "These findings suggest lorlatinib could enhance current immunotherapies. Future studies will investigate combining lorlatinib with ICB therapy.Legal entity responsible for the study J. Simonetti."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD69 • IFNG • IL2RA • PD-1

Exploring the role of FES kinase in natural killer cells to enhance immunotherapy (ESMO-IO 2025) - "In murine tumour models, engrafted tumours were treated with lorlatinib, a potent inhibitor of Fes and Fer, and the tumour microenvironment was immunophenotyped using flow cytometry to assess NK recruitment, activation, and anti-tumour function in vivo.Results Fes-deficient NK cells exhibited enhanced cytotoxicity and activation relative to wild-type controls...Next steps will focus on developing and evaluating Fes-deficient NKs in preclinical models to assess their therapeutic potential. Importantly, this work opens avenues for CAR NK modification, including the generation of Fes-deficient CAR NKs with enhanced cytotoxic capacity for clinical application.Legal entity responsible for the study A.A. Varty-Higgs."

IO biomarker • Oncology • GZMB

Brief Report: Alectinib with salvage platinum-taxane chemotherapy in a pregnant woman with ALK-rearranged NSCLC and rapid disease progression followed by a successful pregnancy. (PubMed, J Thorac Oncol) - "This is the first reported case of concurrent alectinib and cytotoxic chemotherapy during pregnancy, successfully used in the setting of progressive ALK-rearranged NSCLC. The placental findings align with observations in pregnancies complicated by FGR. This case highlights the potential feasibility and safety of intensification of systemic therapy during pregnancy, and underscores the importance of individualised multi-disciplinary care."

Journal • Cardiovascular • Ischemic stroke • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK