Alunbrig (brigatinib)

Notably, C479 exhibited in vitro inhibitory activity comparable to Brigatinib. All the results indicate that the candidate compounds not only possess inhibitory activity similar to that of Brigatinib, but may also help diversify the existing repertoire of ALK-targeted agents and provide additional options for NSCLC research.

Although rare, GI perforation, represents a clinically relevant adverse event associated with alectinib, particularly in patients with diverticulosis or other predisposing conditions. It is essential to optimize safety and long-term disease control by raising awareness of early warning symptoms, conducting a baseline GI evaluation in high-risk patients and carefully sequencing therapy after discontinuation.

Three patients were treated with imatinib (one later switched to nilotinib and then dasatinib), while one patient each received osimertinib and brigatinib. When interstitial pneumonia occurs during TKI administration and does not respond to drug withdrawal and corticosteroid treatment, careful analysis of chest imaging features, along with bronchoalveolar lavage and/or bronchoscopic lung biopsy, is necessary for a definitive diagnosis. This case series and literature review suggest that nebulized GM-CSF or whole lung lavage (WLL) may be effective treatment options for TKI-induced autoimmune PAP.

For EGFR-mutant NSCLC, sequential development of tyrosine kinase inhibitors (TKIs) from first- to third-generation agents-culminating in osimertinib-has markedly improved survival. Similarly, successive generations of ALK inhibitors, including alectinib, brigatinib, and lorlatinib, have extended disease control, particularly within the central nervous system. The introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan for HER2-mutant NSCLC, and emerging TKIs like zongertinib, represent new therapeutic milestones...Beyond lung cancer, our group, in collaboration with Juntendo University ARO (academic research organization) and fifteen institutions in Japan, conducted the MARBLE phase II trial of atezolizumab plus chemotherapy for thymic carcinoma, achieving a 56% objective response rate and 9.6-month median progression-free survival, supporting potential ICI approval in Japan...The DLL3-targeted BiTE tarlatamab significantly improved overall survival to 13.6 months in the phase III DeLLphi-304 trial for relapsed SCLC, with manageable cytokine release syndrome. Collectively, these advances signify a shift toward biologically driven, molecular-targeted or immune-integrated therapy, aiming to transform lung cancer into a chronic, manageable disease in the future, hopefully.

Patients were treated with crizotinib, alectinib, or brigatinib. Our results highlight the high efficacy of ALKi in achieving disease control (DC) in patients with ALK-positive NSCLC, regardless of the specific fusion variant or treatment regimen. However, the subtle differences in stable disease (SD) and PD rates among fusion variants suggest that genetic profiling may be useful in predicting the durability of response.

VS biology reflects integrated genetic and epigenomic dysregulation. Advancing care will require multi-omic classification, biomarker-driven trials, and combination therapies targeting both signaling and epigenetic vulnerabilities. Future management is expected to shift toward personalized, mechanism-based strategies aimed at durable tumor control while preserving hearing and quality of life.

This case highlights the importance of molecular profiling in guiding targeted therapies for rare pediatric gliomas. Further research is needed to address questions regarding the optimal use of ALK inhibitors and their long-term impact on prognosis and neurocognitive development.

Alectinib demonstrated a clear survival advantage over crizotinib, consistent with trial findings. Lorlatinib showed potential benefit over alectinib, though limited by sample size and wide confidence intervals. This study provides the largest claims-based analysis of 1 L ALK TKIs and may help guide differentiation among agents with equivalent guideline placement.

P2, N=109, Recruiting, Scott R. Plotkin, MD, PhD | Active, not recruiting --> Recruiting

This case highlights that clinicians should consider drug-induced pleuritis when pleural effusion develops during brigatinib therapy, particularly when it is inconsistent with the disease progression. Dose reduction to as low as 30 mg/day may be a safe and effective therapeutic option for selected patients.

Furthermore, cell cycle arrest assay, apoptosis induction assays, Western blot assay, colony formation inhibition assay, cell migration inhibition assays, tube formation assay, and docking analysis were carried out to study the action mechanism of compound 8c. All these results indicated that compound 8c has the potential for further evaluation of in vivo efficacy and druggability.

Although FDA (Food and Drug Administration) approved inhibitors such as crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib have improved clinical outcomes, their efficacy is often challenged by resistance mechanisms, including secondary kinase domain mutations and activation of bypass pathways. Binding free energies and per-residue contributions were computed using MMGBSA. Boltz-2 machine learning platform to predict KD values and the top three hits were validated using PCA and free energy landscape.