Alunbrig (brigatinib) / Takeda - LARVOL DELTA

Case Report: Severe brigatinib-induced pneumonitis in a patient with EML4-ALK+ metastatic non-small cell lung adenocarcinoma. (PubMed, Front Oncol) - "The workup for alternative etiologies of respiratory distress was unrevealing, and the patient was treated for presumed brigatinib-induced pneumonitis with high-dose methylprednisolone. This case demonstrates high-grade, rapidly progressive brigatinib-induced pneumonitis with prompt clinical improvement after steroids and a marked disease response without recurring toxicity after treatment with an alternative ALK TKI, alectinib."

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

Successful Treatment of Osimertinib Resistance in an EGFR-Mutant Lung Cancer Patient With a Rare STRN3-ALK Fusion Using Brigatinib and Osimertinib. (PubMed, Kaohsiung J Med Sci) - No abstract available

Journal • Lung Cancer • Oncology • Solid Tumor • EGFR • STRN3

Progression and expansion of ALK inhibitors against NSCLC: A dual target approach. (PubMed, Eur J Med Chem) - "Since the ALK inhibitors such as Crizotinib, Ceritinib, Brigatinib, Alectinib and Lorlatinib, was endorsed for the treatment of advanced NSCLC linked to ALK gene rearrangement. The aim of this review is to summarize the introduction to ALK and the synergy between ALK and other anti-tumor targets, recent developments in the synthesis of various dual inhibitors of the ALK. We also thoroughly discussed their design concepts, structure-activity relationships (SARs), preclinical and clinical data as well as in silico studies to provide ideas for further development of novel ALK based dual inhibitors."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • ROS1

ALK-driven NSCLC and radiotherapy - pro (ESTRO 2025) - "LAURA selected patients with common mutations in EGFR due to the availability of a well-tolerated and efficacious agent (osimertinib), but the findings of this study are likely to be transferable to other such settings...eg. brigatinib, alectinib. A small retrospective series published recently suggests that consolidation ALK-targeted therapy may be more beneficial than durvalumab and no treatment in the scenario where an ALK rearrangement has been identified in the tumour. Prospective evidence is awaited from the ongoing phase 2 BOUNCE trial and phase 3 HORIZON-1 trials, although some patients may ask about off-license use of ALK-targeted therapies in the interim. This presentation will discuss the completed and ongoing studies in the 'ALK-positive' NSCLC chemoradiation setting and explore the implications of these data."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • EML4

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) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

Real-world comparative outcomes of alectinib and brigatinib in ALK-positive non–small cell lung cancer: A retrospective cohort analysis using HIRA data. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Real-world • Real-world evidence • Retrospective data • 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 | "Clinical Trial Registration Number: NCT05361564 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

Disproportionality Analysis of ALK Inhibitor-Induced Hemolytic Adverse Events: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database. (PubMed, Can J Physiol Pharmacol) - "The findings highlight alectinibs potential hemolytic risk, necessitating hematologic monitoring. Proposed mechanisms include immune-mediated hemolysis, direct cytotoxicity, and metabolic variability. Routine hemoglobin and bilirubin assessments, along with clinical vigilance, are essential. Further studies are needed to elucidate mechanisms of causality and optimize patient safety."

Adverse events • Journal • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Inter-Ethnic Differences in the Efficacy and Safety of Tyrosine Kinase Inhibitors Used in Oncology: Insights From Phase 3 Clinical Trials. (PubMed, Clin Transl Sci) - "Twelve (16%) of the analyses investigating the efficacy of afatinib, brigatinib, dacomitinib, gilteritinib, lorlatinib, neratinib, osimertinib, or pazopanib were assessed to report population differences in PFS and/or OS...The majority of clinical trials noted no clinically remarkable differences in safety between subpopulations; however, for brigatinib, crizotinib, pazopanib, and sunitinib, distinct patterns of adverse events were reported in the Asian and non-Asian subgroups. The underrepresentation of specific subpopulations, the grouping together of results of diverse subpopulations, as well as inconsistencies in the definition and reporting of participant ethnicity/ancestry are barriers to the meaningful exploration of inter-ethnic differences in TKI response. Therefore, further insight into the associations between ethnicity/ancestry and TKI response will require an increase in the diversity of clinical trial participants and appropriate analysis and reporting of..."

Journal • P3 data • Review • Oncology

Challenges in Projecting Treatment Journeys for ALK-mutated NSCLC: Addressing Uncertainty in PPS and Immature Overall Survival Data (ISPOR 2025) - "We aimed to evaluate the incorporation of RWE to address the PPS using data from 126 patients with ALK-mutated stage IV NSCLC from Oncoclínicas&Co/MedSir, Brazil between 2007 and 2024. We analyzed RCTs and RWE for patients with ALK-mutated stage IV NSCLC treated with third-generation TKIs: lorlatinib, alectinib, and brigatinib. The lack of a defined PPS standard and immature OS data increases uncertainty in treatment projections. While RWE mitigates gaps, robust sensitivity analyses remain critical to account for variability in post-progression outcomes."

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

Optimized Treatment Sequences for ALK+ Stage IV NSCLC: Cost-Effectiveness Analysis From RCT data and Real-World Evidence (ISPOR 2025) - "This study aims to analyze the cost-effectiveness relationship between randomized clinical trials (RCT) and real-world evidence (RWE) involving 126 patients with ALK-mutated stage IV NSCLC from Oncoclínicas&Co/MedSir, Brazil, between 2007 and 2024. An analytical decision model was developed, considering transitions between six health states: first-line progression-free survival (PFS) with tyrosine kinase inhibitors (TKIs; lorlatinib, alectinib, brigatinib), first-line post-progression survival (PPS), second-line PFS with TKIs, third-line PFS with chemotherapy, PPS, and death. RWE clarified some uncertainties in the model, but the cost-effectiveness ratio remains unfavorable across both models, likely due to the high costs of the evaluated technologies."

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

Cost-Utility Analysis of Lorlatinib in First-Line Treatment of adult patients with ALK-Positive Advanced Non-Small Cell Lung Cancer (aNSCLC) in Colombia (ISPOR 2025) - "In the Colombian health care system setting, lorlatinib is a cost-effective alternative against alectinib, brigatinib and crizotinib for the first-line treatment of adult patients ALK-positive aNSCLC."

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

A Simple and Practical Guide to Implementing Generalized Risk-Adjusted Cost-Effectiveness (GRACE): A Case Study in Non-Small Cell Lung Cancer (ISPOR 2025) - "This study aims to outline a simplified process for implementing GRACE and demonstrates its application by extending a traditional cost-effectiveness analysis (CEA) of three therapies for advanced non-small cell lung cancer (NSCLC) into a GRACE analysis. A traditional CEA model evaluating alectinib, brigatinib, and lorlatinib in advanced anaplastic lymphoma kinase (ALK)-positive NSCLC was extended into GRACE. GRACE analyses can significantly shift cost-effectiveness conclusions and accommodate both societal and patient-centered risk preferences. This study provides a step-by-step guide to extending traditional CEA models into GRACE, demonstrating its feasibility and flexibility in advancing more accurate, comprehensive, and equitable value assessments."

Case study • Clinical • Cost effectiveness • HEOR • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

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) - "R2 was calculated along with 95% confidence intervals (CIs) using a bootstrapping method. 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 strong associations between OS and both PFS and ORR among TKI-treated patients with ROS1+ aNSCLC, lending support to previous real world evidence evaluating surrogacy of PFS. However, uncertainty was substantial and 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

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

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

Clinical practice guideline on anaplastic lymphoma kinase-tyrosine kinase inhibitors for non-small cell lung cancer (2025 edition) (PubMed, Zhonghua Zhong Liu Za Zhi) - "As of December 31, 2024, eight ALK-TKIs, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, iruplinalkib, and invonalkib have garnered approval from the China National Medical Products Administration (NMPA) (Ranking according to the approval time for marketing by NMPA), providing targeted treatment agents for ALK-positive NSCLC patients. To standardize the application of ALK-TKIs, The Chinese Association for Clinical Oncologists and the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care has organized experts to compile the "Clinical practice guideline on anaplastic lymphoma kinase-tyrosine kinase inhibitors for non-small cell lung cancer (2025 edition)". This guideline provides recommendations in four aspects, encompassing ALK fusion testing, ALK-TKI targeted therapy, ALK-TKI adverse events management, and patient post-treatment follow-up, thus serving as a valuable..."

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

Short‑term efficacy assessment of brigatinib for the treatment of neurofibromatosis type 2: A retrospective study. (PubMed, Oncol Lett) - "However, no significant improvement was seen in acoustic neuroma volume or the mean hearing threshold (both P>0.05). In conclusion, brigatinib may relieve meningiomas and pain and improve emotional well-being in patients with NF2."

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

Identification of genes associated with drug persistence/resistance using CRISPR screening and scRNA-seq of ALK rearranged lung cancer (AACR 2025) - "Cas9 and genome-wide sgRNA-introduced cells were cultured with alectinib or lorlatinib for 9 days, and sgRNAs in surviving drug-tolerant cells were analyzed by NGS...In contrast, NF2 knockout itself induces drug resistance rather than drug persistence, and we found that brigatinib may be able to overcome the resistance induced by NF2 loss, because brigatinib inhibited ALK as well as several other kinases at single digit nM...Single-cell RNA sequencing revealed that MMP11-positive cancer-associated fibroblasts (CAFs) and a subset of tumor-associated macrophages (TAMs) were the major sources of Gas6 in the tumor microenvironment. This study uncovered some of the unidentified resistance mechanisms and potential therapeutic strategies to overcome the resistance."

Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • AXL • CAFs • EGFR • ERRFI1 • GAS6 • MMP11 • NF2 • PTEN

Evaluation of lorlatinib efficacy using plasma DNA (AACR 2025) - "This study is the first to analyze lorlatinib's efficacy in such patients by integrating ctDNA analysis to explore predictive markers and resistance mechanisms. This multi-center prospective study enrolled patients with ALK-rearranged NSCLC resistant to alectinib, with no prior exposure to ALK-TKIs other than alectinib and brigatinib. This exploratory study highlights the complexity of resistance mechanisms in ALK-rearranged NSCLC treated with lorlatinib, demonstrating ctDNA's potential as a predictive biomarker for treatment outcomes. The persistence and emergence of specific mutations, such as in TP53 and ALK, underscore the need for further investigation into combination or personalized therapeutic strategies. Despite the study's limited sample size, these findings offer critical insights into the genomic landscape influencing lorlatinib efficacy following alectinib resistance."

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

UNLOCK, a preclinical platform of PDX models resistant to innovative therapies (AACR 2025) - P=N/A | "These models are developed across several cohorts, including castration-resistant prostate cancer (22 PDX: 18 AR pathway inhibitors, 1 post-PARPi, and 3 Lu-PSMA), lung cancer (40 PDX with EGFR inhibitors, including 28 post-osimertinib, and 22 PDX with ALK inhibitors, including 2 post-brigatinib, 9 post-lorlatinib, and 6 post-alectinib). The development of 197 PDX models under the UNLOCK program represents a significant resource, enabling the evaluation of novel drugs, adaptive treatment strategies, and combinatorial approaches. This unique collection of PDX models paves the way for advancing precision oncology and overcoming therapeutic resistance."

Preclinical • Biliary Cancer • Bladder Cancer • Castration-Resistant Prostate Cancer • Cholangiocarcinoma • Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • FGFR2 • FGFR3 • KRAS

Brigatinib Plus Chemotherapy or Local Consolidation Therapy in ALK Positive Advanced Non-small Cell Lung Cancer (BrightStar-2) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=168 ➔ 0 | Trial completion date: Dec 2031 ➔ Apr 2025 | Recruiting ➔ Withdrawn | Trial primary completion date: Dec 2029 ➔ Apr 2025

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

Effectiveness of First-Line Treatment with Anaplastic Lymphoma Kinase and ROS1 Protoncogene Inhibitors in Non-Small Cell Lung Cancer Patients-Real-World Evidence of Two Polish Cancer Centers. (PubMed, Cancers (Basel)) - "In this retrospective study, we compare the efficacy of crizotinib, brigatinib, and alectinib in NSCLC patients with different clinical courses of the disease. Second-generation ALK inhibitors are more effective than crizotinib in ALK-rearranged patients. Liver metastases, but not brain metastases, are the main clinical factors shortening PFS and OS in NSCLC patients treated with ALK inhibitors."

HEOR • Journal • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

First-Line Alectinib, Brigatinib, and Lorlatinib for Advanced ALK-Positive Non-Small Cell Lung Cancer: A Cost-Effectiveness Analysis. (PubMed, Value Health) - "While our model slightly favors brigatinib at a $150,000/QALY willingness-to-pay threshold, substantial uncertainty precludes definitive cost-effectiveness conclusions among the three first-line therapies."

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

CUBIK: Clinical Utility of Liquid Biopsy in Brigatinib ALK+ Patients (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Fundación GECP | Trial completion date: Apr 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Nov 2025

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

Effectiveness of First-Line Treatment with Anaplastic Lymphoma Kinase and ROS1 Protoncogene Inhibitors in Non-Small Cell Lung Cancer Patients-Real-World Evidence of Two Polish Cancer Centers (Multidisciplinary Digital Publishing Institute) - 'In this retrospective study, we compare the efficacy of crizotinib, brigatinib, and alectinib in NSCLC patients....In ALK-rearranged patients, ORR was insignificantly higher in patients treated with second-generation ALK inhibitors than in patients receiving crizotinib (68.25% vs. 48% of patients, p = 0.0547). Median PFS in the crizotinib group was 8 months, and in the group that received second-generation ALK inhibitors this was not reached (HR = 5.2182, 95% CI: 2.6163–10.4079, p < 0.0001). Similarly, median OS was significantly lower in patients treated with crizotinib than in patients receiving second-generation ALK inhibitors (26 vs. not reached, HR = 3.529, 95% CI: 1.5559–7.2258, p = 0.002). The efficacy of crizotinib in patients with ROS1 and ALK gene rearrangement did not differ significantly (ORR—37.5 vs. 48%, median PFS—6 vs. 7 months, median OS—8 vs. 26 months, respectively)."

Retrospective data • Non Small Cell Lung Cancer