Alunbrig (brigatinib) / Takeda - LARVOL DELTA

Molecular Pathogenesis, Genetic Profiles, and Therapeutic Strategies for NF2-Related Schwannomatosis (PubMed, No Shinkei Geka) - "Targeted therapies-including bevacizumab, brigatinib, and vascular endothelial growth factor -A vaccines-have shown promise, particularly in refractory cases. Although routine intensive surveillance is not universally required, early genetic screening and long-term follow-ups may benefit select individuals. The comprehensive integration of genetic, pathological, and immunological data is essential for advancing personalized treatment strategies for NF2-SWN."

Journal • Review • Brain Cancer • CNS Tumor • Genetic Disorders • Meningioma • Neurofibromatosis • Oncology • Solid Tumor • NF2

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

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

Real-world costs, treatment patterns, and clinical outcomes associated with treatments for advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. (PubMed, J Manag Care Spec Pharm) - "Among 696 patients, the 1L therapy distribution was crizotinib (n = 366), alectinib (n = 267), brigatinib (n = 22), ceritinib (n = 25), and lorlatinib (n = 16). This study highlights the economic burden and variable clinical outcomes among patients with advanced ALK+ NSCLC. These real-world estimates inform cost-effectiveness analyses and clinical decision-making regarding treatment sequencing, particularly given uncertainty surrounding multiple preferred 1L options in clinical guidelines."

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

Alectinib Efficacy Post-Brigatinib Against Advanced ALK+ Non-Small Cell Lung Cancer (BrigALK2-GFPC 02-2019 Study). (PubMed, Lung Cancer (Auckl)) - "Brigatinib and alectinib are next-generation anaplastic lymphoma kinase inhibitors (ALKis) showing efficacy against naïve and post-crizotinib-treated advanced ALK+ non-small-cell lung cancers (NSCLCs). For patients receiving ≥1 agent(s) between brigatinib and alectinib, with median follow-up at 13.3 (95% CI: 2.3-31.5) months, mPFS and mOS were 5.0 (95% CI: 0.5-18.8) and 19 (95% CI: 2.3-NR) months, respectively. According to the results of this retrospective real-world study, alectinib post-brigatinib showed limited overall activity but remains an option for patients with advanced ALK+ NSCLCs, especially when brigatinib was discontinued because of toxicity."

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

A real-world pharmacovigilance analysis of ALK inhibitor-associated pleural and pericardial effusion using the FDA Adverse Events Reporting System (FAERS) database from 2013 to 2024. (PubMed, PLoS One) - "This study highlights the critical need for vigilant pharmacovigilance and a multidisciplinary approach to balance the oncologic benefits of ALK inhibitors against their cardiopulmonary risks. By enhancing awareness and fostering proactive management, these findings aim to support the safe and effective use of ALK inhibitors in treating ALK-rearranged malignancies."

Adverse events • Journal • Real-world evidence • Cardiovascular • Oncology • ALK

Contemporary Landscape of Acquired Resistance to Next-Generation ALK Inhibitors: Paired Pre-/Post-Treatment Biopsy Analysis (IASLC-WCLC 2025) - "Methods : This retrospective study included patients treated with second-generation (2G; alectinib, brigatinib, ceritinib) and/or third-generation (3G; lorlatinib) ALK TKIs with paired (pre- and post-TKI) biopsies assessed with next-generation sequencing (NGS)...Among patients without prior crizotinib, MET amplification was more frequent on post- versus pre-lorlatinib biopsies (22.2% vs 2.8%, p=0.016)...MET amplification represents a recurrent off-target AR mechanism and highlights the critical role for post-TKI biopsies to enable consideration of ALK/MET co-inhibition. NGS does not identify putative AR mechanisms for significant proportion of patients, emphasizing a need to investigate non-genomic AR mechanisms."

Biopsy • Preclinical • Lung Cancer • Oncology • Solid Tumor • ALK • CDKN2A • CDKN2B • EGFR • KEAP1 • MET • NF1 • NOTCH2 • SETD2 • SMAD4 • SMARCA4 • TP53

Insights on Treatment Experience From Patients With ALK+ NSCLC Treated With 1St-Line Brigatinib, Lorlatinib and Alectinib (IASLC-WCLC 2025) - "These data illustrate the multifaceted impact of ALK-TKI treatment on daily life, highlighting the importance of addressing both physical and psychosocial dimensions of patient care. These findings emphasize the importance of patient experience considerations in treatment decisions for ALK+ NSCLC."

Clinical • Asthma • Fatigue • Gastroesophageal Reflux Disease • Immunology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Pneumonia • Respiratory Diseases • Solid Tumor • ALK

Brilliant First Analysis: A Real-World Study of Characteristics and Safety About Brigatinib as First-Line for Chinese Patients With ALK+ NSCLC (IASLC-WCLC 2025) - P | "The study observed that pts with locally advanced stage IIIA and IIIC received brigatinib treatment in real-world clinical practice. Real-world effectiveness and post-treatment will continue to be evaluated."

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

Effectiveness and Treatment Patterns in Patients With First-Line 2G ALK TKI Across the Esme French Real-World Cohort (IASLC-WCLC 2025) - "Introduction : The ESMO guidelines recommend alectinib, brigatinib (second-generation [2G]) or lorlatinib (third-generation [3G]) anaplastic lymphoma kinase inhibitors (ALKis) as the preferred first-line (1L) treatments for ALK+ advanced non-small-cell lung cancer (aNSCLC). Conclusions : Results of this study are consistent with previous results, highlighting the unmet need with 2G ALK TKIs. This supports thoughtful consideration of 1L treatment with the longest systemic and intracranial efficacy upfront to provide the greatest benefit for patients with ALK+ aNCSLC."

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

Optimizing Treatment Sequencing to Maximize Survival in ALK+ Advanced Non-Small Cell Lung Cancer: A Modeling Study (IASLC-WCLC 2025) - "Additional ALKis, such as NVL-655 is under investigation...Results : 1L lorlatinib sequences yielded the longest PFS overall, with ~5 years of additional PFS vs 1L therapy with alectinib or brigatinib (Table and Figure)...Conclusions : Based on current evidence and modeling assumptions, initial treatment with 1L lorlatinib may yield the longest PFS vs 2nd gen TKIs, regardless of types of subsequent treatments. This highlights the importance of initiation of 1L treatment with the longest demonstrated PFS upfront."

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

A Real-World Study of Advanced ALK-Fusion NSCLC Patients Receiving First-Line ALK-TKI Therapy with Telehealth Care (IASLC-WCLC 2025) - "Progression-free survival (PFS) and adverse events (AEs) were compared among patients treated with different ALK-TKIs, including alectinib, brigatinib, and lorlatinib. Multivariate regression analysis in the alectinib group identified adherence to WeDoc telehealth protocols and close doctor-patient communication as independent factors associated with prolonged PFS, without significant impact on side effects or patient-reported outcomes. Conclusions : The use of WeDoc, a telehealth system, for managing advanced NSCLC patients on long-term ALK-TKI therapy in real-world practice is linked to prolonged PFS, warranting validation through future randomized controlled trials."

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

Prospective observational study of brigatinib after alectinib in ALK-positive, non-small cell lung cancer: efficacy and biomarker analyses from Cohort A of the WJOG11919L/ABRAID trial (ESMO 2025) - No abstract available

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

Randomized, open-label, phase II study of brigatinib and carboplatin plus pemetrexed and brigatinib alone in chemotherapy-naïve patients with ALK-positive non-squamous non-small cell lung cancer: Interim safety analysis of the WJOG14720L (ESMO 2025) - No abstract available

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

Direct Ser797 Interacted Pteridine-7(8H)-one Derivatives as Highly Selective and Orally Available EGFRL858R/T790M/C797S Inhibitors. (PubMed, J Med Chem) - "The EGFRC797S mutation is the main mechanism of acquired resistance to Osimertinib in NSCLC. Moreover, M49 demonstrated effective antitumor efficacy in BaF3-EGFRL858R/T790M/C797S xenograft model in comparison with Brigatinib (TGI = 73.53% vs 56.05%). In all, this study provided a novel EGFRLR/TM/CS inhibitor discovery strategy and a pteridin-7(8H)-one-based EGFRLR/TM/CS inhibitor which exhibited great potency and selectivity both in vitro and in vivo."

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

ALK inhibitor brigatinib-related photo-onycholysis. (PubMed, Eur J Dermatol) - No abstract available

Journal

OPTALK: Trial for Local Ablative Treatment (LAT) Optimization in Patients With Advanced Non-Small Cells Lung Cancer (NSCLC) Presenting an Anaplastic Lymphoma Kinase (ALK) Rearrangement Treated by Brigatinib (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Groupe Francais De Pneumo-Cancerologie | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2024 ➔ Jun 2025

Enrollment open • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pharmacoeconomic Analysis of Brigatinib versus Alectinib in First‑Line Treatment of Anaplastic Lymphoma Kinase‑Positive Advanced Non‑Small‑Cell Lung Cancer in China. (PubMed, Oncol Ther) - "Brigatinib was a cost-saving (14,203 USD) treatment compared with alectinib in the CMA analysis for the first-line treatment of patients with ALK-positive advanced NSCLC in China."

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

Recent Advances in the Treatment of Non-small Cell Lung Cancer with Brigatinib (PubMed, Zhongguo Fei Ai Za Zhi) - "The next generation of ALK tyrosine kinase inhibitor, Brigatinib, has demonstrated significant efficacy in patients with ALK-positive NSCLC, offering clinical benefits in deep response of tumor, treatment of brain metastases patients, quality of life, and long-term survival. This review will provide current advancements and exploratory directions for Brigatinib.."

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

The Role of Axl Inhibition and Immune Checkpoint Blockade in Non-small Cell Lung Cancer: Current Understanding and Treatment Strategies. (PubMed, Cancer Diagn Progn) - "Preclinical studies highlight the efficacy of Axl inhibitors, such as bemcentinib, brigatinib, and enapotamab vedotin, in overcoming drug resistance and enhancing immune responses. Clinical trials combining Axl inhibitors with ICIs (e.g., pembrolizumab) show promise, particularly in STK11-mutant NSCLC, with manageable toxicity profiles. However, challenges persist in optimizing dosing, managing adverse events, and identifying predictive biomarkers. Ongoing research into combination strategies and biomarker-driven approaches aims to refine Axl-targeted therapies and improve outcomes for patients with advanced NSCLC."

Checkpoint inhibition • IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • STK11

Activity of Brigatinib in Patients With Crizotinib-Resistant ALK-positive Non-Small-Cell Lung Cancer According to ALK Fusion and Mutation Status. (PubMed, Clin Lung Cancer) - "Brigatinib showed substantial activity in crizotinib-pretreated ALK-positive NSCLC with ALK-dependent mechanisms of resistance. Patients with non-ALK canonical drivers did not respond to brigatinib, suggesting alternative therapeutic approaches in that cohort."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • NRAS

Establishment and characterization of NCC-EMC1-C1: a novel patient-derived cell line of extraskeletal myxoid chondrosarcoma. (PubMed, Hum Cell) - "High-throughput screening of 221 anticancer drugs using NCC-EMC1-C1 identified three candidates, brigatinib, panobinostat, and romidepsin, that demonstrated low IC50 values. These data indicated the utility of NCC-EMC1-C1 for the experiments based on screening. We conclude that NCC-EMC1-C1 is a valuable tool for preclinical and basic research on EMC."

Journal • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EWSR1 • NR4A3

Progression-Free Survival and Objective Response Rates As Surrogate Endpoints for Overall Survival Among Patients With ROS1+ Locally Advanced or Metastatic Non-Small Cell Lung Cancer Receiving ROS1 Tyrosine Kinase Inhibitors (ISPOR 2025) - " Twelve cohorts from non-randomized clinical trials involving treatment with crizotinib, entrectinib, lorlatinib, brigatinib or ceritinib were identified; repotrectinib cohorts were excluded. The current analysis demonstrated a strong association between OS and PFS among TKI-treated patients with ROS1+ aNSCLC, lending support to previous real world evidence evaluating surrogacy of PFS. However, OS and ORR demonstrated a weak association with substantial uncertainty. The lack of head-to-head evidence precluded assessment of the correlation between treatment effects."

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

Molecular profiling using NGS in lung cancer patients: Revolutionizing targeted therapy and personalized treatment. (ASCO 2025) - "The hotspot KRAS mutation G12C was detected in 10,3% of cases and it is associated with response to the FDA approved drugs Sotorasib and Adagrasib...Additionally, ALK fusion was detected in 2,2% of patients offering response to on label therapies like Brigatinib and Lorlatinib... The findings described above underline the necessity of a multigene analysis for patients with NSCLC, in order to benefit from the available targeted therapies. PDL-1 testing increases this benefit as it is a positive predictive biomarker for immunotherapy, even for patients harboring no driver mutations."

Clinical • IO biomarker • Next-generation sequencing • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • HER-2 • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • RET • ROS1 • STK11

Real-world baseline characteristics and diagnostic path of Polish patients with ALK-positive NSCLC eligible for brigatinib treatment: Interim results from the ENTIRETY study. (ASCO 2025) - P | "These findings enhance our understanding of the characteristics and diagnostic path of Polish patients with ALK+ NSCLC receiving brigatinib treatment. Patient flow*.*Data based on patient-reported questionnaire unless noted otherwise. # Based on patients' medical history (with no missing values)."

Clinical • Real-world • Real-world evidence • CNS Disorders • Fatigue • Insomnia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Sleep Disorder • Solid Tumor • ALK