nilotinib / Generic mfg. - LARVOL DELTA

To Study the Effect of Nilotinib, a Tyrosine Kinase Inhibitor, on Learning and Memory and Its Comparison with Nitric Oxide Synthase Inhibitor in an Animal Model of Alzheimer's Disease. (PubMed, Ann Neurosci) - "This study aimed to compare the effect of nilotinib (a tyrosine kinase inhibitor) and N ω-nitro-l-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) as agents that improve learning and memory processes in a scopolamine-induced rat model of AD with memantine. Nilotinib demonstrated superior efficacy to L-NAME and may represent a potential therapeutic strategy for AD. Further studies are warranted to evaluate long-term effects and clinical applicability."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Pain

Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI) (ASH 2024) - P2 | "Pts had received prior treatment with imatinib (32.6%), dasatinib (48.8%), nilotinib (16.3%), or bosutinib (2.3%); 76.7% had received their prior TKI for ≥12 mo. These promising results support asciminib as a potential treatment option in these pts. Updated data (data cutoff June 28, 2024) will be presented at the ASH 2024 Annual Meeting."

Clinical • P2 data • Cardiovascular • Chronic Myeloid Leukemia • Cough • Fatigue • Hematological Malignancies • Hypertension • Leukemia • Oncology • Respiratory Diseases

ASCIMINIB (ASC) PROVIDES SUPERIOR EFFICACY AND EXCELLENT SAFETY AND TOLERABILITY VS TYROSINE KINASE INHIBITORS (TKI) IN NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA (CML) IN THE PIVOTAL ASC4FIRST STUDY (EHA 2024) - P3 | "ASC, the first BCR::ABL1 inhibitor to Specifically Target theABL Myristoyl Pocket (STAMP), was intentionally designed to be highly specific and minimize off-target effects.We report primary results from ASC4FIRST (NCT04971226), a randomized ph 3 study of ASC vs all currentstandard-of-care frontline TKIs in pts with newly diagnosed CML.Aims:The two primary objectives were to demonstrate superior major molecular response (MMR) rate at wk 48 withASC vs investigator-selected (IS) TKI and ASC vs IS TKI within the stratum of pts with imatinib (IMA) as theirprerandomization-selected (PRS) TKI (ASCIMA vs IS TKIIMA). Pts received ASC (n=201: ASCIMA, n=101; ASC2G, n=100) or an IS TKI (n=204: IS TKIIMA, n=102; IS TKI2G,n=102 [nilotinib, 48%; dasatinib, 41%; and bosutinib, 11%]). Median follow-up was 16.3 and 15.7 mo with ASCand IS TKIs, respectively. At cutoff (Nov 28, 2023), Tx was ongoing in 86%, 62%, and 75% of pts receiving ASC,IMA, and 2G TKIs, respectively (Figure).MMR..."

Clinical • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

A phase 2 study of nilotinib in pediatric patients with CML: long-term update on growth retardation and safety. (PubMed, Blood Adv) - P2 | "The phase 2, open-label study (DIALOG) of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) met its coprimary end points, showing sustained nilotinib efficacy in patients with newly diagnosed (ND) or imatinib/dasatinib resistant/intolerant (R/I) CML. Apart from the impact on growth, the safety profile of nilotinib was generally consistent with previous reports. This study was registered on www.clinicaltrials.gov at #NCT01844765."

Clinical • Journal • P2 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pain • Pediatrics

ASC4FIRST WK 144 ANALYSIS: CONTINUED SUPERIOR EFFICACY AND FAVORABLE SAFETY OF ASCIMINIB VS INVESTIGATOR-SELECTED TYROSINE KINASE INHIBITORS IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKEMIA (EHA 2026) - P3 | "2025) analyses, asciminib (ASC) had superior efficacy and improved safety/tolerability vs investigator-selected tyrosine kinase inhibitors (IS-TKIs: imatinib [IMA] and second generation [2G] TKIs), and a better benefit-risk profile vs 2G TKIs...No new BCR::ABL1 mutations emerged with ASC after wk 96; 1 each emerged with IMA and nilotinib...Reused with permission. This abstract was accepted and previously presented at the 2026 ASCO Annual Meeting."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

Real-World Impact of Frontline Second-Generation Tyrosine Kinase Inhibitors and Disease Burden on Outcomes in Adult Philadelphia-Positive Acute Lymphoblastic Leukemia (SOHO 2026) - "First-line TKI therapy included imatinib in 52.7%, dasatinib in 41.8%, and nilotinib in 5.5% of patients. Adult PH+ ALL demonstrated high relapse and mortality rates in this real-world cohort. Use of second-generation TKIs was independently associated with significantly improved relapse-free survival compared with imatinib-based therapy. Baseline anemia, elevated LDH, and higher BCR::ABL1 burden were associated with poorer outcomes."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Asciminib (ASC) in Combination with Imatinib (IMA), Nilotinib (NIL), or Dasatinib (DAS) May be a Potential Treatment (Tx) Option in Patients (Pts) with Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase (Ph+ CML-CP/AP): Final Results from the Asciminib Phase 1 Study (ASH 2023) - P1 | "INTRODUCTION: ATP-competitive tyrosine kinase inhibitors (TKIs) have extended the life expectancy of pts with CML. ASC in combination with ATP-competitive TKIs, while associated with a higher AE burden vs ASC monotherapy, demonstrated rapid efficacy in the enrolled pt population. The MTD for ASC + IMA was reached at ASC 60 mg QD + IMA 400 mg QD (Table); the MTD for ASC + NIL or DAS was not reached. ASC 40 or 60 mg QD + IMA 400 mg QD, ASC 40 mg BID + NIL 300 mg BID, and ASC 80 mg QD + DAS 100 mg QD were recommended doses for expansion."

Clinical • Combination therapy • P1 data • Chronic Myeloid Leukemia • Fatigue • Hematological Malignancies • Leukemia • Oncology

Atherothrombotic Adverse Effects of Tyrosine Kinase Inhibitors in Patients With Chronic Myeloid Leukemia (SOHO 2026) - " The patients were receiving imatinib (26 patients; 16%), nilotinib (50 patients; 31%), dasatinib (26 patients; 16%), bosutinib (4 patients; 3%), ponatinib (44 patients; 28%), asciminib (7 patients; 6%), and vamotinib (2 patients; 1%). In patients with CML, ATAEs are associated with initially high CV risk. Nilotinib and ponatinib demonstrated the most unfavorable toxicity profiles. These findings highlight the importance of CV risk assessment before TKI initiation and its dynamic monitoring during treatment."

Adverse events • Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Use of receptor and nonreceptor tyrosine kinase inhibitors and Parkinson disease risk. (PubMed, Neurotherapeutics) - "This study investigated associations between Medicare Part D prescription fills prior to PD diagnosis for 7 rTK inhibitors (erlotinib, sorafenib, pazopanib, imatinib, sunitinib, nintedanib, and dasatinib) and 4 nrTK inhibitors (nilotinib, ibrutinib, ruxolitinib, and tofacitinib) and PD risk. Given the chemotherapeutic mechanisms of these medications, and the known cancer-PD inverse relationship, we performed a sensitivity analysis adjusting for relevant cancer subtypes, yielding a similar inverse association. Overall, the use of rTK and nrTK inhibitors was associated with a lower risk of developing PD, although there may be differential impact of this medication class depending on specific inhibition pathways."

Journal • CNS Disorders • Movement Disorders • Oncology • Parkinson's Disease

Olverembatinib As Second-Line (2L) Therapy in Patients (pts) with Chronic Phase-Chronic Myeloid Leukemia (CP-CML) (ASH 2024) - P2 | "Twelve (28.6%) pts had received 1L imatinib, and 30 (71.4%) had been treated with a 1L 2G TKI, including dasatinib (n = 5, 11.9%), nilotinib (n = 11, 26.2%), or flumatinib (n = 14, 33.3%). Conclusions This is the first study report of olverembatinib in 2L CP-CML treatment. Olverembatinib may provide an effective and safe 2L treatment option for pts with CP-CML, especially those failing on 1L 2G TKIs."

Clinical • Anemia • Cardiovascular • Chronic Myeloid Leukemia • Hypertension • Neutropenia • Thrombocytopenia • ABL1 • BCR

Asciminib (ASC) Add-on to Imatinib (IMA) Demonstrates Sustained High Rates of Ongoing Therapy and Deep Molecular Responses (DMRs) with Prolonged Follow-up in the ASC4MORE Study (ASH 2023) - P2 | "Here, we report results of ASC add-on to IMA vs continued IMA vs switch to nilotinib (NIL) and of pts who crossed over from continued IMA to ASC add-on after 96 wks of Tx in pts not achieving DMR with ≥1 y of IMA as their first TKI (cutoff: 6 Mar 2023)...The top reasons for discontinuation were pt decision (9.5% with ASC 40 mg add-on), adverse events (AEs; 14.3% and 33.3%, with ASC 60 mg add-on and NIL, respectively), and physician decision (66.7% with IMA, all of whom crossed over to ASC 60 mg add-on)... Among pts not achieving DMR after ≥1 y on IMA, more pts achieved MR4.5 with ASC add-on to IMA than with continuing IMA or switching to NIL at wk 96. Pts crossing over from IMA to ASC 60 mg add-on were still able to achieve DMRs. ASC add-on to IMA was well-tolerated, with no new or worsening safety findings compared with those known for ASC alone."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Safety and Efficacy of Tgrx-678, a Potent BCR::ABL1 allosteric Inhibitor, in Patients with Tyrosine Kinase Inhibitor Resistant and/or Intolerant Chronic Myeloid Leukemia: Updated Results of Phase 1 Study Tgrx-678 -1001 (ASH 2024) - P1, P2 | "Methods : In phase Ia, CML-CP and CML-AP patients who were R/I at least to imatinib, dasatinib and nilotinib were enrolled...Patients were heavily pretreated; 71 (66%) CP and 44 (88%) AP patients had received ≥ 3 prior TKIs; 40 (37%) CP and 30 (60%) AP patients had previously received ponatinib, olverembatinib, asciminib, and/or HS-10382 (a new STAMP inhibitor)...The updated data indicate promising efficacy in both CP and AP patients including those with the T315I mutation and those who failed 3G-TKI or STAMP inhibitors. Ongoing Phase 2 trials in China (NCT NCT06453902) and Phase 1 trials in US (NCT06088888) are further evaluating TGRX-678, underscoring the need for continued assessment."

Clinical • P1 data • Anemia • Chronic Myeloid Leukemia • Diabetes • Dyslipidemia • Hypertriglyceridemia • Leukopenia • Metabolic Disorders • Neutropenia • Thrombocytopenia • ABL1

Asciminib vs Dasatinib/Nilotinib as First-Line Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: A Propensity Score-Matched Analysis of Disease Progression and Safety Outcomes (SOHO 2026) - "The primary end point was disease progression between days 90 and 270, defined as escalation to ponatinib or omacetaxine, hematopoietic stem cell transplantation, or transformation to acute leukemia. The progression difference did not reach statistical significance, partly reflecting insufficient power to detect a moderate effect. Retrospective claims-level ascertainment of progression is imperfect, as some therapy switches may not represent true disease advancement. The cytopenia reduction with asciminib was substantial and statistically significant."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • BCR

A Case Report and Literature Review of Acute Myeloid Leukemia With P190-Positive BCR :: ABL Fusion Gene (SOHO 2026) - "P190 BCR::ABL-positive AML is extremely rare; has nonspecific clinical and morphological manifestations; and is easily misdiagnosed as acute lymphoblastic leukemia. Definitive diagnosis relies on molecular detection of the P190 subtype, and immunophenotyping is crucial to confirm myeloid origin. This highly aggressive subtype exhibits poor response to standard AML induction chemotherapy and extremely poor short-term prognosis."

Case report • Clinical • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ANPEP • CD123 • CD33 • CD34 • CD7 • IL3RA • KIT

Efficacy and Safety of Ponatinib as a Second‑Line Treatment for Chronic‑Phase Chronic Myeloid Leukemia: Retrospective Study at Two Japanese Centers. (PubMed, Indian J Hematol Blood Transfus) - "The TKIs administered as first-line treatment were as follows: bosutinib in eight patients (50%), dasatinib in six patients (38%), and nilotinib in two patients (13%). Five patients (31%) discontinued ponatinib. Ponatinib demonstrated high efficacy in treating CML-CP resistant or intolerant to second-generation TKIs."

Journal • Retrospective data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

A Novel BCR::ABL1 I502 T Mutation Associated With Acquired Asciminib Resistance in Chronic-Phase Chronic Myeloid Leukemia (SOHO 2026) - "Case: A 41-year-old woman with CP-CML was initially treated with imatinib for 5 years before transitioning to nilotinib for molecular relapse...Critically, I502 T retained sensitivity to dasatinib (IC50 0.3 nM) and ponatinib (IC50 0.7 nM)... I502 T is a novel myristoyl pocket mutation that confers high-level asciminib resistance while retaining sensitivity to ATP-competitive TKIs, further expanding the landscape of resistance at this critical drug-binding interface. ATP: adenosine triphosphate, BCR::ABL1: breakpoint cluster region–Abelson murine leukemia viral oncogene homolog 1, ERK: extracellular signal-regulated kinase, IC50: half-maximal inhibitory concentration, S6: ribosomal protein S6, STAT5: signal transducer and activator of transcription 5, VAF: variant allele frequency, WT: wild-type."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • RPS6 • STAT5

Repurposing Anticancer Drugs in Parkinson's Treatment: Molecular Pathways Driving Neuroprotection and Therapeutic Advancement. (PubMed, Mol Neurobiol) - "Ixazomib enhances α-synuclein clearance via autophagy in preclinical models. Nilotinib showed poor CNS penetration (< 0.3% in CSF), resulting in worsening motor outcomes. Relatlimab, trehalose, and lapatinib demonstrated preclinical benefits through inhibition of α-synuclein spread, mTOR-independent autophagy, and multi-pathway neuroprotection, respectively. The AZA-PD Phase 2 trial (azathioprine) demonstrated a favourable safety and tolerability profile and offered valuable insights into peripheral immune modulation in early PD, though it did not meet its primary endpoint of slowing disease progression...Mechanistic convergence provides a rationale for repurposing drugs; however, clinical success requires addressing the unique challenges of neurodegeneration. Future approaches should focus on precision medicine, innovative delivery systems, and multi-target interventions rather than direct therapeutic translation."

Journal • Review • CNS Disorders • Immune Modulation • Immunology • Metabolic Disorders • Movement Disorders • Oncology • Parkinson's Disease • Targeted Protein Degradation

Target Attainment and Clinical and Biochemical Parameters Associated with the Pharmacokinetics of 12 Tyrosine Kinase Inhibitors. (PubMed, Clin Pharmacokinet) - "Target attainment was suboptimal for most TKIs, supporting the need for TDM-guided optimisation and individualised dosing. Associations between TKI exposure and renal, hepatic, and haematological parameters further support personalised treatment strategies."

Journal • PK/PD data • Hematological Disorders • Oncology

Cardiac Safety of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Real-World Propensity-Matched Comparison of Dasatinib, Nilotinib, and Imatinib (SOHO 2026) - "Dasatinib was associated with 28%–31% higher 3-year mortality vs both imatinib and nilotinib, while cardiac-specific event rates did not differ significantly across any pairwise TKI comparison. The mortality excess with dasatinib was not explained by the cardiac endpoints, suggesting non-cardiac mechanisms (eg, pulmonary toxicity) may contribute. Prospective evaluation with cause-of-death adjudication is warranted before these signals inform front-line TKI selection."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ABL1 • BCR

Treatment-free remission after two nilotinib consolidation durations in chronic myeloid leukemia treated with imatinib: Phase 3 ENESTPath results. (PubMed, Leukemia) - "In the TFR phase, MR4.0 rates at 12 months (Arm 1: 31.9%, Arm 2: 37.5%; p = 0.383) and 24 months (Arm 1: 29.4%, Arm 2: 30.8%) revealed no differences in TFR success between 2 and 3 years of nilotinib. Irrespective of the consolidation duration, switching to nilotinib 300 mg BID provided the opportunity to achieve TFR if patients were unable to reach stable DMR with first-line imatinib."

Journal • P3 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Olverembatinib (HQP1351) Demonstrates Efficacy Vs. Best Available Therapy (BAT) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant Chronic Myeloid Leukemia Chronic-Phase (CML-CP) in a Registrational Randomized Phase 2 Study (ASH 2023) - P2 | "Introduction This was a multicenter, randomized, registrational phase 2 study to assess the efficacy and safety of olverembatinib compared with BAT in pts with CML-CP who were resistant and/or intolerant to 3 TKIs (imatinib [I], dasatinib [D], nilotinib [N]) in China...Pts were randomized 2:1 to investigational olverembatinib (40 mg QOD) or the BAT arm, which could be one of the following per investigator choice: TKIs (I, D, or N), interferon (IFN), hydroxyurea (HU), and homoharringtonine (HHT)...Olverembatinib was observed to be better tolerated and more effective than BAT in treating these pts. Internal study (CT.gov) numbers: HQP1351CC203 (NCT04126681)."

Clinical • P2 data • Anemia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Leukemia • Leukopenia • Myocardial Infarction • Neutropenia • Oncology • Thrombocytopenia • ABL1

ASC4FIRST, a pivotal phase 3 study of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic myeloid leukemia (CML): Primary results. (ASCO 2024) - P3 | " Adults with CML were randomly assigned 1:1 to receive ASC 80 mg once daily or an IS TKI at standard label doses, stratified by ELTS risk category and prerandomization selected (PRS) TKI (imatinib [IMA] or second-generation [2G] TKIs), which was selected by investigators before randomization, accounting for pt preference... Pts received ASC (n=201: ASC IMA , n=101; ASC 2G , n=100) or IS TKI (n=204: IS TKI IMA , n=102; IS TKI 2G , n=102 [nilotinib, 48%; dasatinib, 41%; bosutinib, 11%])... ASC is the only agent to show a statistically significant superior efficacy and excellent safety and tolerability vs all current standard-of-care frontline Tx, with potential to be the therapy of choice for CML."

Clinical • Late-breaking abstract • P3 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Prescription Behaviour and Drug Interactions of Acid Suppressants With Tyrosine Kinase Inhibitors in Patients With Leukaemia: Data From Germany. (PubMed, EJHaem) - "Results indicate substantial co-prescription rates involving dasatinib, nilotinib, imatinib, bosutinib and ponatinib, with variations across years and agents. The findings highlight the need for improved prescriber awareness, adherence to guidelines and risk mitigation strategies such as therapeutic drug monitoring or alternative dosing. Collaborative efforts between clinicians and regulatory bodies are essential to minimize risks and optimize patient outcomes."

Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

A machine learning approach identifies a transcriptomic signature predicting treatment-free remission in chronic myeloid leukemia (ASH 2025) - P=N/A | "While some clinical andbiological factors have been shown to be associated with TFR, there is currently no validated score topredict TFR in the clinical setting, and the factors underlying molecular relapse are still poorlyunderstood.The main objective of this study was to use transcriptomic data to predict TFR before imatinib (IMA)cessation in patients with CML.MethodsPatients enrolled in the STIM2 multicenter trial (ClinicalTrials.gov, NCT01343173) and with availablefrozen peripheral blood cells (PBC) sample before IMA cessation were included in the main cohort (n=96patients)...Molecular relapse afterTKI cessation was defined as loss of MMR at 1 point.Additional patients with available frozen PBC just before IMA or nilotinib (NIL) cessation from threeFrench academic centers (Centre Hospitalier Lyon Sud, Centre Leon Bérard, Institut Bergonié) wereincluded in the independent validation cohort (n=72 patients, including n=37 IMA and n=35 NIL..."

Clinical • Machine learning • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1 • IL2 • STAT5 • TNFA

Asciminib in combination with imatinib, nilotinib, or dasatinib in patients with chronic myeloid leukemia in chronic or accelerated phase: phase 1 study final results. (PubMed, Leukemia) - "Based on these safety, tolerability, and preliminary efficacy results, asciminib 40 mg twice daily (BID) plus nilotinib 300 mg BID, asciminib 40 or 60 mg once daily (QD) plus imatinib 400 mg QD, and asciminib 80 mg QD plus dasatinib 100 mg QD were identified as recommended doses for expansion. The maximum tolerated dose was reached at asciminib 60 mg QD plus imatinib 400 mg QD and was not reached with asciminib plus nilotinib or dasatinib."

Journal • P1 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology