Alunbrig (brigatinib) / Takeda - LARVOL DELTA

HLH in Disguise: A Diagnostic Puzzle in Treated ALK-Rearranged NSCLC (ESMO Asia 2025) - "Brigatinib was initiated in November 2022, resulting in rapid symptom relief and durable partial response without progression for three years...Etoposide was initiated, but her condition deteriorated rapidly and she died shortly after...This case highlights the diagnostic complexity of persistent fever in oncology patients with stable primary disease. In solid malignancies, HLH should prompt early and thorough evaluation for secondary causes—particularly lymphoma, which is more common—to enable timely and appropriate treatment."

B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lung Adenocarcinoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • ALK • CD20 • EGFR • IRF4 • Napsin A • NKX2-1

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

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

Briga-PED: Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors (clinicaltrials.gov) - P1/2 | N=65 | Recruiting | Sponsor: Princess Maxima Center for Pediatric Oncology | Trial completion date: Dec 2030 ➔ Dec 2033 | Trial primary completion date: Dec 2029 ➔ Dec 2033

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Solid Tumor

Cost-utility and budget impact analyses of anaplastic lymphoma kinase inhibitors in Thailand. (PubMed, Sci Rep) - "Sensitivity analyses confirmed that none of the ALK inhibitors were cost-effective compared to chemotherapy. The five-year BIA estimated the budget impact of ceritinib (450 mg/day, 750 mg/day), alectinib (600 mg/day, 1,200 mg/day), and brigatinib at 2,345 (63.81), 3,703 (100.76), 9,830 (267.49), 19,328 (525.92), and 9,502 (258.56) million THB (USD), respectively."

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

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

Updated results on brigatinib treatment for progressive tumors in patients with NF2-related schwannomatosis: a sub-study of the INTUITT-NF2 trial (SNO 2025) - "The most common AEs were diarrhea (65%), nausea (40%), muscle cramps (40%), hypertension (35%), increased LDH (35%), increased AST (33%), and increased ALT (25%). Conclusion : Brigatinib treatment was associated with high rates of tumor stability at 24 months across multiple tumor types in patients with NF2-related schwannomatosis."

Clinical • Brain Cancer • Cardiovascular • Ependymoma • Hypertension • Meningioma • Oncology • Solid Tumor

TEAD inhibitor VT3989, in combination with Brigatinib prevents NF2-deficient meningioma and schwannoma growth. (SNO 2025) - "Further validation of these processes is underway to identify synthetic lethality targets and determine the mechanism behind VT3989 and brigatinib synergy. Together, our data demonstrates the therapeutic efficacy of VT3989 in combination with brigatinib, highlighting its potential clinical benefit for future NF2-SWN patients."

Combination therapy • Brain Cancer • Ependymoma • Meningioma • Solid Tumor • NF2 • POSTN

Updated results on brigatinib treatment for progressive tumors in patients with NF2-related schwannomatosis: a sub-study of the INTUITT-NF2 trial (SNO 2025) - "The most common AEs were diarrhea (65%), nausea (40%), muscle cramps (40%), hypertension (35%), increased LDH (35%), increased AST (33%), and increased ALT (25%). Conclusion : Brigatinib treatment was associated with high rates of tumor stability at 24 months across multiple tumor types in patients with NF2-related schwannomatosis."

Clinical • Brain Cancer • Cardiovascular • Ependymoma • Hypertension • Meningioma • Oncology • Solid Tumor

TEAD inhibitor VT3989, in combination with Brigatinib prevents NF2-deficient meningioma and schwannoma growth. (SNO 2025) - "Further validation of these processes is underway to identify synthetic lethality targets and determine the mechanism behind VT3989 and brigatinib synergy. Together, our data demonstrates the therapeutic efficacy of VT3989 in combination with brigatinib, highlighting its potential clinical benefit for future NF2-SWN patients."

Combination therapy • Brain Cancer • Ependymoma • Meningioma • Solid Tumor • NF2 • POSTN

Central Nervous System Progression in Patients Receiving ALK-Targeted Central Nervous System-Penetrable Tyrosine Kinase Inhibitors: Treatment Patterns and Outcomes. (PubMed, JTO Clin Res Rep) - "This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (p = 0.21). For patients with ALK-rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI."

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

Updated results on brigatinib treatment for progressive tumors in patients with NF2-related schwannomatosis: a sub-study of the INTUITT-NF2 trial (WFNOS 2025) - "The most common AEs were diarrhea (65%), nausea (40%), muscle cramps (40%), hypertension (35%), increased LDH (35%), increased AST (33%), and increased ALT (25%). Conclusion : Brigatinib treatment was associated with high rates of tumor stability at 24 months across multiple tumor types in patients with NF2-related schwannomatosis."

Clinical • Brain Cancer • Cardiovascular • CNS Tumor • Ependymoma • Glioma • Hypertension • Meningioma • Oncology • Solid Tumor

TEAD inhibitor VT3989, in combination with Brigatinib prevents NF2-deficient meningioma and schwannoma growth. (WFNOS 2025) - "Further validation of these processes is underway to identify synthetic lethality targets and determine the mechanism behind VT3989 and brigatinib synergy. Together, our data demonstrates the therapeutic efficacy of VT3989 in combination with brigatinib, highlighting its potential clinical benefit for future NF2-SWN patients."

Combination therapy • Brain Cancer • Ependymoma • Meningioma • Solid Tumor • NF2 • POSTN

TEAD inhibitor VT3989, in combination with Brigatinib prevents NF2-deficient meningioma and schwannoma growth. (WFNOS 2025) - "Further validation of these processes is underway to identify synthetic lethality targets and determine the mechanism behind VT3989 and brigatinib synergy. Together, our data demonstrates the therapeutic efficacy of VT3989 in combination with brigatinib, highlighting its potential clinical benefit for future NF2-SWN patients."

Combination therapy • Brain Cancer • Ependymoma • Glioma • Meningioma • Oncology • Solid Tumor • NF2 • POSTN

Updated results on brigatinib treatment for progressive tumors in patients with NF2-related schwannomatosis: a sub-study of the INTUITT-NF2 trial (WFNOS 2025) - "The most common AEs were diarrhea (65%), nausea (40%), muscle cramps (40%), hypertension (35%), increased LDH (35%), increased AST (33%), and increased ALT (25%). Conclusion : Brigatinib treatment was associated with high rates of tumor stability at 24 months across multiple tumor types in patients with NF2-related schwannomatosis."

Clinical • Brain Cancer • Cardiovascular • Ependymoma • Glioma • Hypertension • Meningioma • Solid Tumor

IFCT-2101 MASTERPROTOCOL ALK: Study of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK) (clinicaltrials.gov) - P2 | N=110 | Active, not recruiting | Sponsor: Intergroupe Francophone de Cancerologie Thoracique | Trial primary completion date: Apr 2025 ➔ Sep 2025

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

Targeting IGF1R/Insr Pathway with Approved ALK-Inhibitors Overcomes Proteasome Inhibitor Resistance in Multiple Myeloma (ASH 2023) - "Background: The treatment of multiple myeloma (MM) has advanced rapidly with the discovery of proteasome inhibitors (PIs) bortezomib (BTZ) and carfilzomib (CFZ)...The combination of ceritinib, brigatinib, and entrectinib showed synergistic cytotoxicity with PI BTZ and CFZ and overcame PI-resistance in four different sets of PI-adapted cells... Ceritinib, an FDA-approved drug, overcomes PI resistance in MM by targeting InsR/IGF1R signaling, which is essential for PI resistance in MM. Therefore, ceritinib represents a promising, potential option for the treatment of PI-resistant MM."

Hematological Malignancies • Multiple Myeloma • Oncology • DDIT4 • IGF1 • IGF1R • IR • TSC1

The Impact of Clinical Evidence on the Inclusion of Non-Small Cell Lung Cancer Drugs in Brazil's Supplementary Healthcare System (ISPOR-EU 2025) - "Favorable recommendations were issued for brigatinib, lorlatinib as first-line treatment, and osimertinib, all supported by Phase 3 trials, with network meta-analyses for brigatinib and lorlatinib. Unfavorable decisions were observed for lorlatinib as a second-line treatment, tepotinib, and selpercatinib, which relied primarily on Phase 2 data, although selpercatinib also included some Phase 3 evidence... Regulatory decisions by ANS are influenced by the robustness of clinical trial evidence. These findings suggest that submissions relying solely on early-phase studies may face greater barriers to approval. This analysis provides valuable insights for optimizing future drug submission strategies within Brazil's supplementary healthcare system."

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

Predictive value of baseline and longitudinal MRI radiomics for intracranial progression-free survival in ALK-positive NSCLC patients with brain metastases (SITC 2025) - "This study aimed to evaluate the predictive performance of MRI-based radiomic features, assessed at baseline and first follow-up, for iPFS in this population.Methods Retrospective data from 98 ALK+ NSCLC patients with brain metastases treated with ALK TKIs (brigatinib, crizotinib) were analyzed. The exploratory lesion-level volumetric response model showed moderate discrimination (AUC 0.70) but was impacted by dataset class imbalance (92% controlled lesions).Conclusions Longitudinal delta radiomic features, capturing dynamic changes between baseline and early follow-up MRI scans, significantly enhance the prediction of iPFS compared to using only baseline features in ALK+ NSCLC patients with brain metastases receiving TKI therapy. These findings highlight the potential of dynamic radiomic analysis, integrating multi-sequence MRI data, as a powerful non-invasive tool for prognostication and monitoring treatment response.Abstract 512 Figure 1Request permissionsROC Curve or..."

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

Association Between ALK Tyrosine Kinase Inhibitor and the Risk of Interstitial Lung Disease and Pneumonitis in Non-Small Cell Lung Cancer Patients: A Systematic Review (ISPOR-EU 2025) - "In the network meta-analysis (NMA), brigatinib was associated with significantly higher risks of both overall ILD and overall pneumonitis than crizotinib (OR=8.87, 95%CI: 1.07 to 73.29; OR=3.43, 95%CI: 1.00 to 11.71, respectively), alectinib (OR=12.78, 95%CI: 1.56 to 104.98; OR=6.09, 95%CI:1.57 to 23.68, respectively) and ceritinib (OR=32.50, 95%CI: 1.05 to 1005.95; OR=21.88, 95%CI: 1.78 to 268.53, respectively). ALK-TKIs increase the risks of both ILD and pneumonitis in NSCLC patients, with brigatinib posing the highest risks among ALK-TKIs."

Clinical • Review • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ALK

Response to a combination of T-DXd (Trastuzumab-Deruxtecan) plus Alectinib in a patient with ALK-TKI resistant ALK+ NSCLC harboring a common polymorphism MET N375S (DGHO 2025) - "From 2021 to 2023 the patient received sequential ALK-TKIs, including alectinib (9 months, mixed response ), lorlatinib (4 months, PD), brigatinib (4 months, PD) followed by atezo/bev/pac/carbo with a partial remission lasting for 6 months At no time point, on- or off target resistance alterations were detectable. In molecular pathology, NGS is primarily appointed to detect clinically relevant alterations, with a focus on hotspot mutations in driver oncogenes. However, a multitude of putatively benign polymorphisms are detected alongside and their contribution to a given therapy may be complex and potentially underestimated. Close genetic disease monitoring, continuous updates of annotation databases and discussions in molecular tumor boards may help to guide treatment options."

Clinical • Genetic Disorders • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Respiratory Diseases • Solid Tumor • ALK • EML4 • LRRTM4 • TP53

Brigatinib Monotherapy in Children with R/R ALK+ ALCL, IMT, or Other Solid Tumors: Updated Results from the Brigaped (ITCC-098) Phase 1 Dose-Escalation Study (ASH 2024) - P1/2 | "The phase 2 part of this study is currently open for accrual with disease-specific cohorts for ALK+ ALCL and IMT (age ≥1 - <26 years). An age-appropriate formulation is in development and will be used to confirm the RP2D in smaller children."

Clinical • Monotherapy • P1 data • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ophthalmology • Pediatrics • Sarcoma • Solid Tumor • ALK

BET proteins mediate survival mechanisms in human schwannoma model cells challenged with trametinib but not brigatinib. (PubMed, Oncogene) - "However, this response is not observed when BET inhibitors are combined with brigatinib, a multi-kinase inhibitor in clinical use. These findings highlight the complex cellular adaptations in schwannomas and suggest that targeting BET alongside MEK inhibition prevents resistance mechanisms and promotes cell death."

Journal • Brain Cancer • CNS Disorders • Solid Tumor • BRD4 • JUN

"Tumor mutational burden (TMB) and proliferation as negative prognostic factors for ALK+ lung cancer - first results from the randomized ABP phase 2 trial" (DGHO 2025) - "Aurora kinase A was the most significant member of all three categories with HR 2.33 (p=7E-6) and 2.84 (p=0.0027) for PFS and OS per doubling of gene expression.Brigatinib and alectinib upfront result in comparable median PFS of 2.5 - 3 years. Despite low values, TMB reveals a stronger link with clinical outcomes than other features, while a proliferation signature emerges as potential novel molecular risk factor."

Biomarker • Clinical • P2 data • Tumor mutational burden • Lung Cancer • Oncology • Solid Tumor • ALK • AURKA • EML4 • HRD • TMB • TP53