Tasigna (nilotinib)

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: Jul 2025 --> Dec 2025

P2, N=40, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting

We found that TKIs, such as imatinib, nilotinib, and dasatinib, increased the gene expression of PRDX2 in K562 cells; however, only dasatinib increased the cytoplasmic protein expression of PRDX2. This discrepancy was linked to post-translational regulation through SUMOylation in cooperation with dasatinib. Our results suggest that the antioxidants PRDX1 and PRDX2 could serve as potential targets for TKIs in the treatment of CML.

We therefore conducted a confirmatory, preclinical multicenter randomized controlled replication trial to test the safety and efficacy of three drugs for preventing paclitaxel-induced polyneuropathy: (1) nilotinib, (2) lithium carbonate and (3) interleukin-6-neutralizing antibodies. Thus, although lithium carbonate and IL-6-neutralizing antibodies tended toward neuroprotection, the differences between these groups were not statistically significant. However, the PINPRICS study ultimately still provides important lessons with regard to the planning and conduction of multicenter preclinical trials.

P2, N=160, Not yet recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto | Trial completion date: Sep 2031 --> Jun 2032 | Initiation date: Sep 2024 --> Jun 2025 | Trial primary completion date: Sep 2028 --> Jun 2029

Nilotinib was screened as a candidate inhibitor of SRD5A3 and was confirmed to remarkably decrease cancer cell metastasis...The supernatant from SPP1+ macrophage significantly enhanced the expression of SOX4/SRD5A3 and the metastatic ability of cancer cells, and this effect was reversed by the deletion of SPP1. Collectively, our findings illuminate the SPP1-SRD5A3 signaling as the crucial driver in LNM and suggest that its blockade could be a promising option for overcoming LNM.

Its binding affinity to Caspase-7 is evidently highlighted by immunofluorescence assay as well as in-silico docking study which further establishes its efficacy in elucidating apoptotic activity. Based on the findings, it can be concluded that NLB functions effectively in BC when loaded into BSA nanoparticles (NLB-BSA-NPs) in vitro.

Based on this study, it would be advisable to identify the key DRLs with potential prognostic value in BLCA to enhance the evaluation of clinical outcomes in this context.

P2, N=163, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

We observed that certain transcriptome features present at diagnosis persisted after 12 months of nilotinib treatment, compared to CTRLs. This suggests that nilotinib may exert selective pressure, potentially supporting the survival and self-renewal of LSCs. Future insights into these pathways could help identify therapeutic targets to improve outcomes in CML.

The reporting odds ratios and their 95% confidence intervals for BCR-ABL inhibitor monotherapy, asciminib, nilotinib, and ponatinib were 1.31 (1.27-1.36), 2.11 (1.45-3.06), 2.66 (2.53-2.80), and 1.18 (1.05-1.33), respectively. Dasatinib plus triazole antifungal agents (reporting odds ratio: 2.98, 95% CI: 1.93-4.60) and ponatinib plus triazole antifungal agents (reporting odds ratio: 1.53, 95% CI: 1.08-2.16) were associated with a higher disproportionality of cardiac arrhythmias than BCR-ABL inhibitor monotherapy. The median time-to-onset was longer with monotherapy than with BCR-ABL inhibitors plus triazole antifungal agents (2.63 vs. 0.34 months, p < 0.001), both indicating an early failure type. BCR-ABL inhibitors plus triazole antifungal agents increase the risk of cardiac arrhythmia, particularly in the early stages of treatment, with the risk decreasing over time.

Immunotherapy, as well as Palbociclib and Perifosine, were predicted to be more effective for low-risk patients. Conversely, high-risk patients were more likely to benefit from Axitinib, Imatinib, Nilotinib, and Temsirolimus. This study identified 5 signature genes as potential biomarkers and therapeutic targets for THCA. These findings provide novel insights into the prognosis and targeted therapy of THCA, offering a foundation for furture clinical applications.

P2, N=104, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Six BCR::ABL1 TKIs have been approved by the US Food and Drug Administration, including 5 that are first-line treatment (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and 5 approved for treatment after disease progression despite initial therapy (dasatinib, bosutinib, nilotinib, ponatinib, asciminib). Many patients require continuous TKI therapy. Therefore, TKI therapy should be selected with consideration of adverse effects, and patients should be helped to maximize adherence to TKI treatment.

Imatinib (first generation), dasatinib, nilotinib and bosutinib (second generation) and ponatinib (third generation) are the five approved TKIs that inhibit BCR::ABL1 by binding to the ATP binding site of ABL1. In this review we detail the mechanism of action, preclinical data, clinical data, safety and tolerability of asciminib. Due to its mechanism of action, asciminib has fewer off target effects, resulting in an improved safety and tolerability profile.

P2, N=215, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P2, N=144, Completed, Ascentage Pharma Group Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Aug 2024 | Trial primary completion date: Dec 2024 --> Aug 2024

This study compared responses of three commonly used CML cell lines (K562, LAMA84, KCL22) to five TKIs (imatinib, nilotinib, dasatinib, bosutinib, ponatinib) and a Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor commonly used in clinical settings. This comprehensive comparison provides valuable insights for refining preclinical models and enhancing translational relevance in CML research and treatment development. Understanding the diverse responses of CML cell lines to TKIs and STAMP inhibitor facilitates the selection of appropriate models for specific research questions, ultimately improving the accuracy and reliability of preclinical studies in CML.

Bosutinib attenuated both thrombin and parasite-induced barrier alterations, while nilotinib was only effective against thrombin, and imatinib protected against neither. Our findings provide important mechanistic insight into the activities of BCR-ABL drugs to suppress endothelial barrier disruptive signaling in vitro and protect in a mouse model of CM. These findings can inform the repurposing of these drugs in malaria treatment, particularly for managing cerebral complications.

P1, N=11, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=20 --> 11 | Trial completion date: Jan 2024 --> Jul 2025 | Trial primary completion date: Jan 2024 --> May 2025

Nilotinib could deteriorate relaxation ability and temporal electrical integrity of the heart through impairing Ca2+ dynamics as well as repolarization phase, which were exacerbated by nilotinib-induced EAD. However, the drug only formed "trigger", which would explain the lower occurrence of nilotinib-induced torsade de pointes.

P1, N=30, Recruiting, Ruta Arays | N=15 --> 30

P2, N=17, Active, not recruiting, Andrew J. Wagner, MD, PhD | Trial completion date: Jul 2025 --> Jul 2026

An evaluation of the genetic profile of uridine diphosphate glucuronosyltransferase was made, as nilotinib inhibits the activity of this enzyme causing hyperbilirubinemia, with higher risk in slow metabolizers, such as those ones with *6/*6 genotype. This type of patient can be identified by genetic profiling, and adjustment in the dose of nilotinib could be made to avoid tyrosine kinase inhibitor switching.

Our study included standard-of-care agents (eg, imatinib and nilotinib) and second-generation ABL inhibitors, including ponatinib and bosutinib, designed to mitigate drug resistance. SIGNIFICANCE STATEMENT: This study examines the effects of clinically relevant small molecule breakpoint cluster region (BCR)-ABL tyrosine kinase inhibitors (TKIs) on platelet activity. This analysis includes first-time assessments of agents such as asciminib and ELVN-919 on human platelet function ex vivo, alongside established therapies (eg, imatinib, ponatinib) with well characterized effects on platelet function, to discern potential antiplatelet and other effects of BCR-ABL TKIs and inform clinical safety.

The F311I subline was sensitive to dasatinib but moderately resistant to imatinib and nilotinib, while the T315I subline and the F311I/T315I subline were highly resistant to these TKIs. Notably, the T315I subline and the F311I/T315I subline were sensitive to therapeutic concentrations of ponatinib, although more resistant than the F311I subline. Moreover, the T315 subline and the F311I/T315 subline were sensitive to asciminib at therapeutic concentration, as was the F311I subline. This is the first human leukemia model in which the impact of the T315I-inclusive compound mutation on TKI sensitivity was directly confirmed.

P4, N=34, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Our study showed a similar frequency of cardiovascular events between men and women. Accurate cardiovascular risk stratification with HFA-ICOS score in cancer patients is crucial. Diabetes and the HFA-ICOS score were significant predictors of events in the female groups. A sex approach in clinical practice could be pursued to improve the appropriateness of care.

Using in vitro proliferation assays on newly generated Ba/F3 cell lines, we confirmed that the mutation confers moderate resistance to ponatinib, and to imatinib and nilotinib. This shift confers resistance to TKIs that preferentially bind to the inactive conformation, as well as to the allosteric asciminib inhibitor. However, the mutation retains sensitivity to dasatinib, which targets the active form of the kinase.

ES patients in the high-risk group exhibited a poorer prognosis, had a higher proportion of myeloid-derived suppressor cells (MDSCs) and M2 type of tumor-associated macrophages, and showed heightened sensitivity to some antitumor agents such as nilotinib and olaparib. This study is the first to construct a disulfidptosis-related prognostic signature that may predict the prognosis and immune response in ES patients, thereby providing a new reference for understanding the mechanisms of ES and guiding immunotherapy.

The ability to distinguish molecular response between lines of therapy is demonstrated using model-based analysis. These nilotinib information enable the extrapolation of novel tyrosine kinase inhibitors (e.g., asciminib) response to other lines of therapy in patients with CML-CP.

We investigated the levels of RNLS in the blood of CML patients in the chronic phase, treatment naïve patients, and those in remission under TKI treatment (either imatinib or nilotinib) and compared them to healthy individuals. Unlike other malignancies studied, RNLS plasma levels are significantly decreased in CML. In future perspectives, RNLS could potentially serve as a diagnostic, prognostic, or therapeutic option for these patients.

Several second-generation tyrosine kinase inhibitors (2GTKIs), such as nilotinib, dasatinib, bosutinib, and radotinib (RTB), followed the groundbreaking introduction of imatinib. This review is the first attempt that extensively presents a compilation of data on RTB and describes its therapeutic potential against blood and solid tumors. Further investigations on RTB could expand its chemotherapeutic usage in various solid tumors and enhance the possibility of drug repurposing in cancer therapy.

The patient was started on nilotinib therapy...This case pinpoints the importance of comprehensive study when MDS is present with deletion 20q and a t(9;22), as it can be misdiagnosed as CML. While definitive therapeutic guidelines have yet to be established for this rare presentation of MDS, the use of tyrosine kinase inhibitors is under investigation.

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

Collectively, GFPT2 is potentially useful as a biomarker for prognostic prediction and immune infiltration in a variety of malignancies ,and could lead to exciting new approaches to personalized oncotherapy.

Further, nilotinib treatment did not affect the expression of genes associated with neuronal health and mitochondrial functioning. Taken together, our findings do not support the efficacy of nilotinib treatment for neuroprotection.

The primary treatment for chronic myeloid leukemia (CML) involves first- and second-generation tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, bosutinib, and dasatinib. It includes in silico calculations, such as the octanol/water partition coefficient (cLogP) via SwissAdme, and 2D maps of intermolecular interactions through molecular docking. This approach enhances understanding for both specialists and those interested in medicinal chemistry and pharmacology, while also contextualizing future directions for further optimizations of ponatinib, facilitating the development of new analogs of this crucial inhibitor for the treatment of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).

The results imply that MEF2C could be a valuable indicator for predicting outcomes and a possible target for immunotherapy for LUAD patients.

Interestingly, the other prominent TKIs Nilotinib and Imatinib did not exert similar effects on muscle cell physiology. Collectively, we identified an unanticipated transcriptional mechanism underlying Sorafenib-induced cachexia. Our findings hold the potential to strategize therapy regimens to minimize chemotherapy-induced cachexia.

As tyrosine kinases serve pivotal roles in platelet hemostatic function, we investigated the potential impact of both established and emerging ABL TKIs on human platelet activities ex vivo Our study included standard-of-care agents (e.g., imatinib and nilotinib), and second-generation ABL inhibitors including ponatinib and bosutinib designed to mitigate drug resistance. Significance Statement This study examines the effects of clinically relevant small molecule BCR-ABL tyrosine kinase inhibitors (TKIs) on platelet activity. This analysis includes first-time assessments of agents such as asciminib and ELVN-919 on human platelet function ex vivo, alongside established therapies (e.g., imatinib, ponatinib) with well-characterized effects on platelet function, to discern potential anti-platelet and other effects of BCR-ABL TKIs and inform clinical safety.

Our disulfidptosis-related lncRNA signature comprised of AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1 could serve as a prognostic biomarker and guidance to therapy response for OC patients.