Alunbrig (brigatinib) / Takeda - LARVOL DELTA

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

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

Updated results on brigatinib treatment for progressive tumors in patients with NF2-related schwannomatosis: a sub-study of the INTUITT-NF2 trial (WFNOS 2025) - "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. (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

Updated results on brigatinib treatment for progressive tumors in patients with NF2-related schwannomatosis: a sub-study of the INTUITT-NF2 trial (WFNOS 2025) - "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

"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

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

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

Sex differences in the tolerability to novel targeted therapies: Insights from a French lung cancer data system (ESMO 2025) - "The most used TTs were Osimertinib (71.5%), Alectinib (15.1%), Lorlatinib (5.4%), Brigatinib (3.9%), Dabrafenib+Trametinib (6.3%), Sotorasib (1.7%), Trastuzumab and Amivantamab (0.6% each), others comprising 1.5%. Our study underscore the need for sex-informed supportive care strategies and inclusive toxicity reporting in clinical trials of TTs. Legal entity responsible for the study Gustave Roussy."

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

PANOBINOSTAT OUTPERFORMS TARGETED THERAPIES IN SYNOVIAL SARCOMA PATIENT-DERIVED TUMOR XENOGRAFT ORGANOIDS (PDXOS) (SIOP 2025) - "While current therapies for SS include ifosfamide and doxorubicin, their efficacy is limited, and surgical resection combined with radiotherapy remains the standard for localized disease...PDXO-1 was treated with panobinostat (HDAC inhibitor), selumetinib, trametinib (MEK inhibitors), and alectinib, brigatinib, lorlatinib (ALK inhibitors) for 24 and 48 hours...These findings highlight the potential of HDAC inhibition as a promising therapeutic approach for SS, particularly for cases with limited response to current treatments. Acknowledgments: FAPESP (2023/14392-0); PRONON SIPAR 25000.211368/2019-41."

Clinical • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • SS18

Patient-derived organoid facilitating personalized medicine in non-small cell lung cancer: two case reports. (PubMed, Front Oncol) - "The corresponding PDO model demonstrated sensitivity to a combination of pemetrexed, carboplatin, and osimertinib, but insensitivity to osimertinib monotherapy...The patient had progressed on multiple lines of therapy, including alectinib and lorlatinib. The PDO model showed sensitivity to brigatinib but insensitivity to ensartinib. Subsequent treatment with brigatinib induced a PR that was sustained for 5.8 months; the patient survived for a total of 9 months following the initiation of this PDO-guided therapy. These two cases suggests that PDOs derived from primary and metastatic lesions may help optimize treatment regimens for patients with lung cancer brain metastases, thereby enabling personalized therapy and potentially improving survival outcomes."

Journal • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • EML4 • NRXN1

Successful and On-going Long-Term Disease Control (>24 Months) with Gilteritinib in an ALK+ NSCLC Patient with Brain Metastasis Who Has Progressed on Multiple ALK TKIs. A Case Report and Review of Literature on Gilteritnib. (PubMed, Lung Cancer (Auckl)) - P1 | "Despite the approval to date of 3 generations of ALK tyrosine kinase inhibitors (TKIs) and the clinical development of a 4th-generation ALK TKI, neladalkib (NVL-655), patients still eventually progress on sequential treatment of various generations of ALK TKIs...Since then, she has been treated with multiple ALK TKIs including crizotinib, alectinib, brigatinib, and lorlatinib sequentially (from age 75 to 80) but requiring dose reduction and interruption of lorlatinib due to neurocognitive toxicity from previous stereotactic brain radiation and resection and eventual discontinuation of lorlatinib...This is the first patient case report with >24 months on-going follow-up demonstrating that gilteritinib could be repurposed as a potent and tolerable ALK inhibitor based on previously reported pre-clinical activity and with potential CNS activity. A Phase 2 trial of gilteritnib in alectinib- or lorlatinib-refractory ALK+ NSCLC is being planned (NCT07140016)."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • EML4 • ROS1

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) - P=N/A | "Conclusions In this large prospective study of post-alectinib cases, brigatinib appeared to be effective regardless of the presence of ALK resistance mutations, including G1202R. Together with the safety profile consistent with previous reports, these findings suggest that brigatinib may be an appropriate treatment option in this setting."

Biomarker • Clinical • Observational data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • TP53

Comparative effectiveness of first-line (1L) tyrosine kinase inhibitors (TKIs) in ALK+ metastatic NSCLC (mNSCLC) by presence of brain metastases (BM) (ESMO 2025) - "Table: 1985P Multivariable Cox PH regression model results Reference: Crizotinib 1L Cohort HR (95% CI) Overall With BM Without BM TTD Alectinib 0.42 (0.36-0.49) 0.32 (0.24-0.42) 0.47 (0.39-0.56) Brigatinib 0.41 (0.27-0.61) 0.32 (0.16-0.64) 0.44 (0.26-0.75) Lorlatinib 0.38 (0.25-0.58) 0.25 (0.12-0.50) 0.47 (0.28-0.81) TTNT Alectinib 0.41 (0.35-0.48) 0.30 (0.22-0.40) 0.47 (0.39-0.57) Brigatinib 0.46 (0.29-0.71) 0.33 (0.16-0.68) 0.53 (0.30-0.91) Lorlatinib 0.35 (0.22-0.56) 0.21 (0.11-0.43) 0.47 (0.25-0.85) OS Alectinib 0.49 (0.40-0.61) 0.38 (0.26-0.56) 0.52 (0.40-0.68) Brigatinib 0.51 (0.26-1.00) 0.43 (0.16-1.15) 0.49 (0.19-1.30) Lorlatinib 0.42 (0.23-0.77) 0.22 (0.08-0.64) 0.58 (0.27-1.25) Conclusions 1L brigatinib, alectinib and lorlatinib demonstrated real-world effectiveness vs crizotinib and comparable effectiveness was observed for brigatinib vs alectinib and lorlatinib. Observed effectiveness of brigatinib, alectinib and lorlatinib in pts with/without BM highlights..."

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

Efficacy and safety of brigatinib after alectinib in patients with ALK-positive NSCLC: Integrated analysis of the ALTA-2 and J-ALTA studies. (PubMed, Lung Cancer) - P2 | "This integrated analysis showed that brigatinib has clinically meaningful activity after disease progression on alectinib."

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

Study Compares Effectiveness of First-Line TKIs in Patients With ALK+ NSCLC and Brain Metastases (Cancer Nursing Today) - "Sharmistha Ghosh...and colleagues conducted the study and presented their findings during the European Society of Medical Oncology (ESMO) 2025 Annual Congress....A total of 1,623 patients participated in the study, with 384 patients receiving crizotinib, 1,100 receiving alectinib, 58 receiving brigatinib, and 81 receiving lorlatinib, all in the first-line....The cohorts comparing brigatinib, alectinib, and lorlatinib versus crizotinib demonstrated significant hazard ratios (HR) for TTD and TTNT, overall and within [brain metastases] subgroups...while 'OS results were numerically consistent'."

Clinical data • Real-world • Non Small Cell Lung Cancer

Tumor mutational burden (TMB) and proliferation as negative prognostic factors for ALK+ lung cancer: First results from the randomized ABP phase II trial (ESMO 2025) - P2 | "Conclusions 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 • WT1

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) - "In patients with NSCLC harboring EGFR mutations, gefitinib or osimertinib with chemotherapy significantly prolonged PFS compared with gefitinib or osimertinib monotherapy. No treatment-related death occurred in either group. Conclusions B-DASH study showed that brigatinib combined with carboplatin and pemetrexed is feasible in interim safety analyses."

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

Discovery of a brain-penetrant fourth-generation EGFR inhibitor to overcome the human triple (L858R/T790 M/C797S) mutation. (PubMed, Eur J Med Chem) - "Osimertinib has been approved as the first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC) and exhibits good brain penetration...Here, we report a series of brigatinib derivatives, rationally designed as fourth-generation EGFR inhibitors...It significantly inhibits tumor growth in the NCI-H1975 xenograft tumor model. Based on its excellent in vitro and in vivo properties, compound D18 can be considered a promising candidate for the treatment of EGFR L858R/T790M/C797S triple mutations and brain metastases."

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

Multidisciplinary treatment of advanced or metastatic ALK-positive non-small cell lung cancer: Real-world data on Brigatinib combined with local therapy (OGP-OGTC 2025) - "Combining brigatinib with local therapy appears safe and potentially more effective for advanced ALK positive NSCLC. Further studies are warranted"

Clinical • Metastases • Real-world • Real-world evidence • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • ALK

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

Sex differences in cardiotoxicity of anaplastic lymphoma kinase inhibitors: An analysis of the FDA Adverse Event Reporting System. (PubMed, Oncology) - "This is the first study to identify sex differences in ALK-TKI-associated cardiotoxicity, highlighting a consistent female predominance in reported adverse events. In particular, considering its widespread use and the clinical importance of left ventricular failure, the pronounced disproportionality signal of cardiotoxicity in females associated with alectinib is thought to have substantial clinical impact. These results underscore the need for heightened clinical vigilance and further research into sex-specific risk stratification and preventive strategies for cardiotoxicity in patients receiving ALK-TKIs."

Adverse events • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Real-World Outcomes of Brigatinib Compared to Alectinib as a Second-Line Therapy After Crizotinib in Advanced Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer Patients. (PubMed, Thorac Cancer) - "In crizotinib-refractory ALK-positive NSCLC, systemic efficacy was not significantly different between brigatinib and alectinib; however, alectinib was associated with more favorable intracranial PFS and ORR, which may be partly explained by differences in prior brain-directed local treatments."

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

Efficacy and safety of brigatinib after alectinib in patients with ALK-positive NSCLC: Integrated analysis of the ALTA-2 and J-ALTA studies (Lung Cancer) - "The objective response rate by independent review committee (IRC) was 31 % (95 % CI: 23 %–39 %); median duration of response was 9.2 months (95 % CI: 5.5–19.4). Median IRC-assessed progression-free survival (PFS) was 5.2 months (95 % CI: 3.7–7.3), and overall survival was 25.0 months (16.2–not reached)."

Retrospective data • Non Small Cell Lung Cancer

Case Report: Treatment response of SQSTM1-ALK fusion lung adenocarcinoma to multiple ALK inhibitors. (PubMed, Front Pharmacol) - "This is the first report of a patient with SQSTM1-ALK fusion who experienced different responses after treatment with alectinib, ensartinib, lorlatinib, and brigatinib. We hope that this case provides clinical evidence to guide treatment strategies for this rare variant and further supports the individualized application of ALK-tyrosine kinase inhibitors (TKIs) in patients with non-classical fusions."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4 • SQSTM1