Alunbrig (brigatinib) / Takeda - LARVOL DELTA

Explainable Machine Learning Reveals Clinical and ctDNA Drivers of Systemic and Intracranial Outcomes with First-Line Brigatinib in ALK-Positive NSCLC (ELCC 2026) - No abstract available

Circulating tumor DNA • Clinical • Machine learning • 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) - 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

CUBIK: Clinical Utility of Liquid Biopsy in Brigatinib ALK+ Patients (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Fundación GECP | Trial primary completion date: Nov 2025 ➔ Nov 2026

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

Patterns of Progression with Lorlatinib and Insights into Subsequent Anticancer Therapy Efficacy in Advanced ALK+ NSCLC (IASLC-WCLC 2024) - P3 | "Best Overall Response and Objective Response Rate on First Subsequent Anticancer Therapy Study treatment Lorlatinib Crizotinib First Subsequent Therapy Any ALK TKI (n=23) a Any non-ALK TKI (n=15) b Overall (n=38) Any ALK TKI (n=101) a Any non-ALK TKI (n=8) b Overall (n=109) Objective response rate (95% CI), % c 26.1 (10.2-48.4) 20.0 (4.3-48.1) 23.7 (11.4-40.2) 17.8 (10.9-26.7) 12.5 (0.3-52.7) 17.4 (10.8-25.9) Best overall response, n (%) Complete response 2 (9) 1 (7) 3 (8) 1 (1) 0 1 (1) Partial response 4 (17) 2 (13) 6 (16) 17 (17) 1 (13) 18 (17) Stable disease 1 (4) 3 (20) 4 (11) 23 (23) 0 23 (21) Progressive disease 6 (26) 3 (20) 9 (24) 10 (10) 2 (25) 12 (11) Unknown 3 (13) 5 (33) 8 (21) 9 (9) 4 (50) 13 (12) Not reported, therapy ongoing 7 (30) 1 (7) 8 (21) 41 (41) 1 (13) 42 (39) a Includes alectinib, brigatinib, ceritinib, crizotinib, and lorlatinib. b Includes chemotherapy ± anti-angiogenic, chemotherapy/immunotherapy,..."

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

Cost of managing brain metastases in ALK-positive advanced NSCLC patients receiving first-line ALK TKIs in China. (PubMed, Lung Cancer Manag) - "Limited CIR beyond 12 months existed for brigatinib and ensartinib. Results from the Asian group's CIR aligned with global trials. Due to lower BM CIR, lorlatinib showed higher BM management cost savings compared to crizotinib and alectinib in Chinese 1 L patients."

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

Magnolol suppresses TKI-resistant EGFR-mutant lung cancer by inhibiting EGFR and AXL-cMyc. (PubMed, Eur J Pharmacol) - "Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), particularly osimertinib, remains a major therapeutic challenge in EGFR-mutant lung cancer...These effects were enhanced when combined with brigatinib, a clinically approved multi-kinase inhibitor with activity against mutant EGFR...Collectively, these findings suggest that magnolol exerts multitargeted effects involving inhibition of mutant EGFR, suppression of the AXL-cMyc signaling axis, and disruption of DNA repair, thereby sensitizing resistant tumors to EGFR-TKIs. Magnolol may represent a promising adjuvant strategy for overcoming acquired resistance in EGFR-mutant lung cancer."

Journal • Lung Cancer • Oncology • Solid Tumor • AXL • EGFR • HRD • MYC • RAD51

From class effects to specificity FAERS evidence and network mapping of adverse events in NSCLC targeted therapy. (PubMed, Int J Surg) - "This first NSCLC-focused FAERS comparison integrating four-method signal detection with network analysis delineates reproducible class effects superimposed by drug-specific toxicities. Findings support tailored monitoring (e.g., dermatologic care for EGFR-TKIs; ECG/electrolytes for osimertinib; lipid/CK surveillance for ALK-TKIs; blood pressure/liver testing for RET-TKIs) to inform risk-aware first-line decisions."

Adverse events • Journal • Cardiovascular • Dyslipidemia • Hypertension • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • ROS1

Hepatotoxicity of new-generation ALK inhibitors versus crizotinib in patients with non-small cell lung cancer: A systematic review and meta-analysis. (PubMed, iScience) - "Alectinib, lorlatinib, and brigatinib are associated with lower risks of hepatotoxicity when compared with crizotinib. Lorlatinib conferred a greater reduction in any grades AST than second-generation inhibitors compared to crizotinib. Our findings suggest that the selection of the ALK inhibitor should be individualized based on the specific profile of hepatotoxicity and their efficacy."

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

Brigatinib Versus Alectinib in ALK-positive Non-small Cell Lung Cancer After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial. (PubMed, J Thorac Oncol) - P3 | "Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC. Safety was consistent with the well-established and unique profiles of each drug. The low proportion of patients with ctDNA-detectable ALK fusion may account for prolonged PFS with both drugs in ALTA-3."

Journal • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

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

ALTA-3: A randomized trial of brigatinib (BRG) vs alectinib (ALC) in crizotinib (CRZ)-refractory advanced ALK+ NSCLC (ESMO Asia 2022) - P3 | "Conclusions At the IA, BIRC PFS was numerically similar between arms. No new safety findings were observed, with safety profiles consistent with known BRG and ALC profiles."

Clinical • Anemia • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Breakfast and Non-CE Product Theater/OncLIve Seminar: ALUNBRIG® (brigatinib) for the First-Line Treatment of ALK+ mNSCLC (WLCC 2026) - No abstract available

Clinical • Lung Cancer • Non Small Cell Lung Cancer

Efficacy of Brigatinib in Patients With Advanced Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Who Progressed on Alectinib or Ceritinib: ALTA-2 Study. (PubMed, J Thorac Oncol) - P2 | "In ALTA-2, brigatinib demonstrated limited activity in patients with ALK+ NSCLC post-ceritinib or post-alectinib therapy. Median PFS was longer with brigatinib in patients without baseline detectable plasma ALK fusion."

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

Brigatinib in ALK-Positive ALCL after Failure of Brentuximab Vedotin. (PubMed, N Engl J Med) - No abstract available

Journal • ALK

Efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC: Integrated analysis of the ALTA-1L and J-ALTA trials. (PubMed, Lung Cancer) - P2, P3 | "Brigatinib demonstrated clinically meaningful systemic and intracranial efficacy in patients with ALK TKI-naive ALK+ NSCLC. Safety results were consistent with the known profile for brigatinib."

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

Longitudinal Tracking of ALK-Rearranged NSCLC From Plasma Using Circulating Tumor RNA and Circulating Tumor DNA. (PubMed, JTO Clin Res Rep) - P1 | "We retrospectively analyzed 86 plasma samples from 33 patients enrolled in the BRIGHTSTAR clinical trial assessing local consolidative therapy (LCT) and brigatinib in patients with stage IV or recurrent NSCLC and confirmed ALK rearrangement (NCT03707938) using a targeted next-generation sequencing assay that analyzes ctDNA to detect gene rearrangements and mutations in 80 genes and ctRNA to detect gene arrangements in 36 genes...Plasma cell-free DNA concentrations for patients with detectable ALK rearrangements at baseline were significantly higher than for those without detectable gene fusions (12.3 ng/mL versus 20.2 ng/mL, p = 0.0046). The inclusion of ctRNA in liquid biopsies increased detection of ALK rearrangements and detection at baseline was associated with significantly worse progression-free survival highlighting the added benefit of ctRNA."

Circulating tumor DNA • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

A window of opportunity study for preoperative brigatinib in resectable anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC): WILDERNESS trial. (ASCO 2025) - P2 | "Neoadjuvant brigatinib was effective and safe in patients with resectable ALK-positive NSCLC. Single-cell transcriptomic analysis highlights the balance between effector and regulatory T cell programs as a critical determinant of pathologic response and the clearance of drug-tolerant and persister cancer cells."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD4 • CD8 • FOXP3 • PRDM1

A phase II randomized, open-labelled, multicenter study of safety and efficacy of combination brigatinib and carboplatin-pemetrexed therapy or brigatinib monotherapy as first-line treatment in patients with advanced ALK-positive non–small cell lung cancer (IFCT-2101 MASTERPROTOCOL ALK). (ASCO 2022) - P2 | "Exploratory objectives include the evaluation of early blood ctDNA decrease on patient outcome. The study is enrolling and primary completion date is March 2025."

Clinical • Monotherapy • P2 data • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Phase II study of brigatinib in patients with TKI-naive ROS1-rearranged non-small cell lung cancer (NSCLC):Barossa study. (JSMO 2023) - No abstract available

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Phase 1/2 trial of brigatinib plus panitumumab in patients with osimertinib-resistant EGFR-mutated non-small cell lung cancer harboring EGFR C797S mutation. (PubMed, Cancer Treat Res Commun) - "The clinical development of this combination strategy was discontinued, as brigatinib treatment was not feasible in patients with advanced EGFR-mutated NSCLC resistant to osimertinib."

IO biomarker • Journal • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Brigatinib in NF2-Related Schwannomatosis with Progressive Tumors. (PubMed, N Engl J Med) - P2 | "Brigatinib treatment resulted in radiographic responses in multiple tumor types and clinical benefit in a heavily pretreated cohort of patients with NF2-SWN. (Funded by the Children's Tumor Foundation and others; INTUITT-NF2 ClinicalTrials.gov number, NCT04374305.)."

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

Clinical utility of liquid biopsy for non-small cell lung cancer patients with ALK fusion variants treated with brigatinib (ESMO 2024) - P2 | "Detection rate by ctDNA profiling is higher compared with RNA-based approaches and it is of prognostic significance."

Biopsy • Clinical • Liquid biopsy • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4 • TMB

Expanding therapeutic options for people with NF2-related schwannomatosis: Encouraging results with brigatinib. (PubMed, Neuro Oncol) - No abstract available

Journal • Brain Cancer • Solid Tumor

Dual FAK and EPHA2 targeting by brigatinib tackles PARP inhibitor adaptive survival response in high-grade serous ovarian cancer. (PubMed, Sci Transl Med) - "Moreover, in HGSOC patient-derived xenograft (PDX) models, brigatinib and PARPi combination therapy induced tumor regression and improved overall survival compared with PARPi alone, particularly in models with high FAK and EPHA2. These findings support dual targeting of FAK and EPHA2 as a strategy to achieve effective and durable PARPi responses and identify a promising biomarker-based combinatorial approach using brigatinib and PARPi for HGSOC, particularly the subset characterized by high FAK and EPHA2."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • ALK • EPHA2 • FOSL1 • FRA1

A New Class of Multitargeting PtIV Anticancer Agents: Prodrugs That Release PtII Drugs and Bioactive Moieties Tethered to PtIV via a Tertiary Amine. (PubMed, J Med Chem) - "Herein, we describe the general approach for design and synthesis of PtIV complexes conjugated to organic drugs (brigatinib, osimertinib, adavosertib, and irinotecan) via their tertiary amines. The PtIV prodrugs conjugated to tyrosine kinase inhibitors (TKIs) showed potent anticancer activity in 2D and 3D cancer models by combining the modes of action of platinum and TKi. They inhibited in vivo tumor growth in an LLC model better than brigatinib, osimertinib, and cisplatin with significantly lower body weight loss."

Journal • Oncology