Zykadia (ceritinib)

P3, N=603, Active, not recruiting, Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 --> Jan 2026

This disruption results in enhanced accumulation of protein aggregates, increased protein polyubiquitination, endoplasmic reticulum stress, and activation of apoptotic pathways. Collectively, our findings support the repurposing of ceritinib in combination with carfilzomib as a translationally relevant and safe strategy to circumvent PI resistance in MM, warranting further clinical investigation in the relapsed/refractory disease setting.

P2, N=200, Completed, Melanoma Institute Australia | Active, not recruiting --> Completed | N=1000 --> 200 | Trial completion date: Dec 2028 --> Dec 2025

Together, these findings provide a multidimensional understanding of DILI risks associated with ceritinib combination therapies. By integrating pharmacovigilance signals with physiologically relevant in vitro validation, this study highlights the utility of the human liver organoids for elucidating the mechanisms of hepatotoxicity insights and supporting safer prescribing practices, especially when ceritinib is co-administered with non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen in real-world clinical settings.

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.

P2, N=1000, Active, not recruiting, Melanoma Institute Australia | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2027 --> Nov 2025

Drug sensitivity analysis revealed that tyrosine kinase inhibitors (e.g., ceritinib, imatinib) potently inhibited cancer cell lines in the high PC score group, while inhibitors like acalabrutinib were effective in the low PC score group. Expression of hub genes in KIRC patients was validated using a local cohort and single-cell sequencing. We identified key genes regulating PC infiltration in KIRC and proposed a predictive model that effectively identifies high-risk KIRC patients.

Cisplatin-derived derivatives bearing phenylbutyrate and either crizotinib (complex 3) or ceritinib (complex 7) exhibited the greatest efficacy and selectivity against cancer cells while sparing noncancerous counterparts. Moreover, both agents triggered apoptosis and hallmarks of immunogenic cell death, including calreticulin exposure, ATP and HMGB1 release, and enhanced phagocytosis by macrophages. These findings highlight complexes 3 and 7 as promising multifunctional candidates that combine cytotoxic, anti-invasive, and immune-activating properties, supporting Pt(IV)-kinase inhibitor conjugates as a potential strategy for targeted cancer chemotherapy.

Several ALK inhibitors, like crizotinib, ceritinib, lorlatinib, repotrectinib, and alectinib, have shown different levels of success, but resistance to these treatments is still a big challenge. While ALK inhibitors have shown promise, resistance mechanisms necessitate the development of combination therapies and next-generation inhibitors. Future research should focus on optimizing targeted treatment strategies to improve survival outcomes in pediatric patients with ALK-positive neuroblastoma.

Temporal trends, clinical outcomes, and differences across TKI generations were examined.ResultsSecond-generation ALK-TKIs (e.g. alectinib) showed the most favorable hepatic safety profile, with the lowest observed mortality (3.5%) and hospitalization (13.0%). First-generation TKIs (crizotinib, ceritinib) and newer agents (lorlatinib, entrectinib) were associated with higher fatality rates (12.0%-13.2%)...These findings should be interpreted cautiously given inherent reporting biases. Future priorities include prospective studies, biomarker-integrated risk stratification, mechanistic investigation, and AI-enhanced monitoring to optimize the risk-benefit profile of ALK/ROS1-TKIs.

Furthermore, Akt1-mediated regulation of ACTH was found to occur via Nur77, the transcriptional activator of POMC. In conclusion, Ceritinib effectively suppresses tumor growth and ACTH production in PDOs of both functioning and silent CD, positioning it as a promising therapeutic agent for CD.

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.