Alunbrig (brigatinib)

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.

Combined with different clinical and pre-clinical anticancer compounds such as V9302, CB839, Sutent, Brigatinib, DRB18 significantly increased death of A549 and Panc1 cells. Mechanistically, DRB18 treatment with paclitaxel elevated the expression of Caspases 3 and 9, suggesting GLUT-inhibiting and apoptosis-inducing anticancer mechanisms of DRB18 with paclitaxel. Collectively, our results demonstrate anticancer efficacy of pan class-I GLUT inhibitor DRB18 in combination with paclitaxel, providing a potentially more efficacious therapeutic strategy for treating advanced NSCLC and other cancers.

In contrast, permanent discontinuation was associated with higher weight/BSA in brigatinib/ceritinib/crizotinib-treated patients. Higher weight and larger BSA at the start of ALK TKI treatment were associated with higher likelihood of toxicity, leading to more DRs and TIs-particularly in males and patients receiving alectinib and lorlatinib. However, weight and BSA were not associated with treatment outcomes.

To date, chemotherapy-based treatments remain the standard of care for C797S + NSCLC patients resistant to third-generation EGFR TKIs. However, for T790M-/C797S + patients received a third-generation EGFR TKI as first-line therapy, EGFR-TKI rechallenge, involving a combination of first and third-generation EGFR TKIs or first/second-generation TKIs, may be an optimal strategy.

Comprehensive in vitro evaluations revealed remarkable antiproliferative activity across all derivatives, with BL-5 (norbornene as linker) demonstrating exceptional potency (IC₅₀ = 36.21 nM) against H3122 cells, surpassing both reference SIAIS164018 (BB-1, IC₅₀ = 78.93 nM) and Brigatinib (IC₅₀ = 44.83 nM)...MD simulations provided critical insights, revealing that the BL-1, BL-4 and BL-5 significantly enhanced the ternary complex stability compared to traditional linkers. These findings establish the polyhedral alkanes as novel linkers in PROTAC design, with BL-5 emerging as a particularly promising candidate for targeting ALK.

We previously generated an orthotopic, NF2-deficient meningioma model using the luciferase-expressing Ben-Men-1 cell line established from a sporadic tumor and identified the multi-kinase inhibitor brigatinib and the mTOR kinase inhibitor INK128 to potently impede tumor growth. As the first NF2-SWN-related meningioma cell line, AG-NF2-Men is a unique reagent for investigating meningioma biology and therapeutics. A clinical trial to evaluate the combination of brigatinib with an mTOR inhibitor in NF2-deficient meningiomas is warranted.

These findings underscore the importance of routine cardiovascular monitoring, particularly in older patients and those with atrial arrhythmias.

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.

P1/2, N=65, Recruiting, Princess Maxima Center for Pediatric Oncology | Trial completion date: Dec 2030 --> Dec 2033 | Trial primary completion date: Dec 2029 --> Dec 2033

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.

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.

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.