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

LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib. (PubMed, J Pharm Biomed Anal) - "After the validation, 74 plasma samples were measured in the application phase and all results but one fell within the validated ranges. This assay allows simultaneous quantification of nine novel targeted therapies and supports therapeutic drug monitoring."

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

Beyond the Basics: Exploring Pharmacokinetic Interactions and Safety in Tyrosine-Kinase Inhibitor Oral Therapy for Solid Tumors. (PubMed, Pharmaceuticals (Basel)) - "Pharmacokinetic DDIs can critically impact the efficacy and safety of TKIs such as erlotinib, gefitinib, and pazopanib by affecting their absorption, distribution, and metabolism. Drug-specific toxicities, such as hyperlipidemia with lorlatinib or visual disturbances with crizotinib, must be assessed using specific criteria, with dose adjustments and supportive care tailored to individual patient responses. Thus, optimal TKI therapy relies on managing drug interactions through multidisciplinary care, monitoring, and patient education to ensure safety and treatment efficacy."

Journal • PK/PD data • Review • Cardiovascular • Dyslipidemia • Fatigue • Oncology • Solid Tumor

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) - No abstract available

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

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) - No abstract available

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

Efficacy and safety analysis of lorlatinib for ALK-positive advanced NSCLC: a multicentre real-world study in China. (PubMed, BMC Cancer) - "This real-world evidence demonstrates that Lorlatinib exhibits significant clinical efficacy and intracranial anti-tumor activity in the treatment of ALK + NSCLC patients, whether in first-line or post-first-line treatment, while being well tolerated."

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

Managing lorlatinib together: An overview and practical guide for patients by ALK-positive NSCLC patients and medical experts. (PubMed, Lung Cancer) - "The CROWN study showed that lorlatinib-associated side effects can be managed with dose adjustments, such as lowering the daily dose, without sacrificing treatment effectiveness. This guide, developed collaboratively by patients living with advanced ALK-positive NSCLC and healthcare professionals experienced with managing lorlatinib treatment, aims to help patients understand what to expect from treatment and how to take an informed, active role in their care."

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

A Real-World Pharmacovigilance Analysis of Lorlatinib-Associated Metabolic Effects Using The FDA Adverse Events Reporting System (FAERS) Database From 2013 to 2024. (PubMed, Endocr Pract) - "These findings highlight the need for proactive monitoring and management of metabolic side effects in patients receiving lorlatinib. A multidisciplinary approach-incorporating pharmacologic interventions, lifestyle modifications, and regular monitoring-is essential to mitigate metabolic risks. This study enhances the understanding of lorlatinib's safety profile and informs clinical strategies to balance efficacy and tolerability in ALK inhibitor therapy."

Adverse events • Journal • Real-world evidence • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Oncology • ALK

Lorlatinib in ROS1+ NSCLC With Brain Metastasis (clinicaltrials.gov) - P2 | N=21 | Not yet recruiting | Sponsor: Hunan Cancer Hospital

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Resistance Mechanisms and Sequential Therapies Following 1St Line Lorlatinib in ALK+ NSCLC: A Real-World Study (LORES CTONG2501) (IASLC-WCLC 2025) - "Abstract is embargoed at this time."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • LY6G6D

Insights on Treatment Experience From Patients With ALK+ NSCLC Treated With 1St-Line Brigatinib, Lorlatinib and Alectinib (IASLC-WCLC 2025) - "Abstract is embargoed at this time."

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

Real-World Study in Patients With ALK+ Metastatic Non-Small Cell Lung Cancer (mNSCLC) Treated With First-Line (1L) Lorlatinib (IASLC-WCLC 2025) - "Abstract is embargoed at this time."

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

Biomarker Analysis and Final Efficacy of Lorlatinib in Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "Abstract is embargoed at this time."

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

Lorlatinib-Associated Dyslipidemia: A Multicenter, Retrospective Analysis and Implications for Future Cardiovascular Disease (IASLC-WCLC 2025) - "Abstract is embargoed at this time."

Retrospective data • Cardiovascular • Dyslipidemia • Metabolic Disorders

ENIGMA+: A National, Decentralized, Remote Consent Study for Clinical Data and Biospecimen Collection in Patients with ALK-Positive Advanced NSCLC. (PubMed, Oncologist) - P | "This study highlights the feasibility of a decentralized design to enhance the inclusion of a broader patient population with ALK+ NSCLC. This establishes a scalable framework that may help overcome barriers to patient participation in research, with the goal of improving therapy development and patient outcomes. The ENIGMA+ study accrual and analysis continue (NCT04881916)."

Clinical data • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CDKN2A • CDKN2B • TP53

Long-term efficacy and improved overall survival of lorlatinib in anaplastic lymphoma kinase-rearranged lung cancer: is cure a dream or a reality? (PubMed, Transl Lung Cancer Res) - No abstract available

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

Managing lorlatinib together: An overview and practical guide for patients by ALK-positive NSCLC patients and medical experts (Lung Cancer) - "While lorlatinib has a distinct side effect profile, its side effects are generally manageable. Managing side effects successfully is critical to preserving patient quality of life and promoting adherence to treatment—both of which are key to maximizing the long-term benefits of lorlatinib. The CROWN study showed that lorlatinib-associated side effects can be managed with dose adjustments, such as lowering the daily dose, without sacrificing treatment effectiveness."

Review • Non Small Cell Lung Cancer

Refining Criteria for Choosing the First-Line Treatment for Real-World Patients with Advanced ALK-Rearranged NSCLC. (PubMed, Int J Mol Sci) - "Consequently, the most potent ALK-TKI to date, Lorlatinib, may be considered as the first-line treatment for high-risk patients with unfavorable features, while sequencing of ALK-TKIs may be appropriate for low-risk patients with favorable features. Although ALK signal inhibition is critical in this disease, it may not be sufficient for clinical control due to de novo co-alterations. A more personalized approach to first-line therapy requires consideration of risk factors for each patient."

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

First-line lorlatinib treatment in a 19-year-old patient with ALK-rearranged pulmonary large-cell neuroendocrine carcinoma: a case report and literature review. (PubMed, Anticancer Drugs) - "The patient was diagnosed with ALK-positive LCNEC and treated with lorlatinib and denosumab combination. This case underscores the extreme rarity of LCNEC in adolescents, highlighting that ALK rearrangements, although exceptionally rare in this histological subtype, can have significant therapeutic implications. It further emphasizes the importance of routine molecular profiling in atypical clinical scenarios and supports the utility of targeted therapies in rare tumor subsets."

Journal • Endocrine Cancer • Large Cell Carcinoma • Lung Cancer • Musculoskeletal Pain • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • ALK • CEACAM5 • EML4 • NCAM1 • RET • SYP • TP53

Safety and Efficacy of Lorbrena (clinicaltrials.gov) - P=N/A | N=683 | Recruiting | Sponsor: Pfizer | Trial completion date: Apr 2026 ➔ Jul 2025 | Trial primary completion date: Apr 2026 ➔ Jul 2025

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

Early weight gain as a risk factor for increased maximum weight gain among NSCLC patients on lorlatinib and other ALK tyrosine kinase inhibitors (JTO Clinical and Research Reports) - "A retrospective chart review of patients with ALK-positive NSCLC receiving TKIs at our institution from 1/1/2020-12/31/2023 was conducted....91 patients received 156 treatment lines of TKI. Patients receiving lorlatinib experienced significantly higher maximum weight gain (mean 13.5% [95% CI 10.8-16.2]) than those receiving other TKIs (p<0.001). Any-grade and grade 3 weight gain rates exceeded those from clinical trials. In multivariate modelling, early weight gain of ≥5% within 6 months (p<0.001), lorlatinib use (p=0.007), and age ≤50 (p=0.046) were associated with maximum weight gain. Among patients receiving lorlatinib, early weight gain (p=0.001) remained significantly associated with higher maximum weight gain."

Retrospective data • Non Small Cell Lung Cancer

An in silico evaluation of lorlatinib as a potential therapy for novel amino acid substitutions in the tyrosine kinase domain of the ALK protein associated with cancer. (PubMed, Front Pharmacol) - "Furthermore, protein-ligand interaction analysis revealed critical hydrophobic interactions, hydrogen bonds, and essential halogen bonds reinforcing lorlatinib as a potential utility in treating a broader spectrum of ALK-positive tumors beyond NSCLC. This research underscores the importance of repurposing in silico drugs and highlights the need for continued exploration of ALK mutations in cancer therapeutics."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • ALK

Assessment of two new ROS1+ NSCLC patient-derived cell lines as in vitro models for TKI resistance studies (EACR 2025) - "The IC50 values of unmutated ROS1+ Ba/F3 cells for crizotinib, entrectinib, lorlatinib, repotrectinib and zidesamtinib were 31.4; 44.6; 14.3; 14.9 and 29.9 nM, respectively...Interestingly, these cells were resistant to lorlatinib, while the patient is – after being treated with lorlatinib+cis-platinum+pemetrexed, now currently successfully treated with lorlatinib mono-therapy... In this study we showed that PC1 cells generated from a crizotinib-resistant patient were resistant to all ROS1 inhibitors tested. The G2032R mutated PC2 cells generated from a crizotinib and lorlatinib resistant patient were sensitive to repotrectinib, but not to zidesamtinib. This PC2 cell line can be used to assess off-target resistance mechanism to zidesamtinib."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • ARID1A • CD74 • PIK3CA • PIK3CG • ROS1

Targeting ErbB receptor family to intercept therapy adaptation in ALK-positive lung cancer (EACR 2025) - "The upfront combination treatment of the bulk population with the pan-ErbB inhibitor afatinib along with lorlatinib severely impacted on LTP viability. Overall, these data suggest that in a fraction of ALK-rearranged NSCLC tumors, drug tolerant cells could exploit ErbB signaling to overcome lorlatinib treatment. Targeting the ErbB family in combination with lorlatinib may represent a valuable therapeutic strategy to improve the clinical outcome of these patients by interfering with LTP survival and evolution."

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

LORLATINIB THERAPY IN RELAPSED/REFRACTORY ALK + LYMPHOMAS PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS (EHA 2025) - "Background: ALK+ Lymphomas are aggressive diseases with poor prognosis when chemoimmunotherapy (CIT) and Crizotinib fail...Two pts also received other TKIs (Alectinib and Ceritinib).Lorlatinib was administered daily at a dose of 100 mg.The ORR at one month (M1) was 100% (95% CI: 72-100%): 5 CR and 3 PR.Three pts, 2 ALCL [ATIC::ALK], 1 ALCL [NPM::ALK]), underwent Allogeneic Stem Cell Transplant (ASCT) while in CR and resumed Lorlatinib post-transplant... Our analysis confirms Lorlatinib's efficacy and safety as salvage therapy. Achieving a CR at M1 was found to be the most important prognostic factor for survival. Adverse events are manageable with dose adjustments."

IO biomarker • Alzheimer's Disease • B Cell Lymphoma • CNS Disorders • Dyslipidemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • ALK • CLTC • EML4

Pulmonary Toxicity Associated With Concurrent Lorlatinib and Anti-GD2 Monoclonal Antibody Therapy in Patients With Neuroblastoma. (PubMed, Pediatr Blood Cancer) - "Concurrent use of lorlatinib with anti-GD2 mAbs may be associated with severe pulmonary toxicities. Temporarily withholding lorlatinib during immunotherapy appeared to mitigate this risk."

Adverse events • Journal • Cough • Neuroblastoma • Oncology • Respiratory Diseases • Solid Tumor • ALK