Supect (radotinib) / IL-Yang Pharm, R-Pharm - LARVOL DELTA

Preliminary safety and efficacy of ELVN-001, a selective active site inhibitor of BCR::ABL1, in patients with CML driven by atypical fusion transcripts (ASH 2025) - P1 | "Thepatient discontinued prior imatinib and nilotinib due to lack of efficacy, had a concurrent diagnosis ofMDS (treated with dasatinib plus azacitidine), a prior allogeneic myeloablative stem cell transplant, andwas last treated with asciminib (discontinued due to lack of efficacy)...The patient discontinued prior nilotinib, dasatinib,ponatinib, asciminib and a combination of asciminib and ponatinib due to lack of efficacy...ELVN-001 demonstrated encouraging anti-CML activity in patients with atypical transcripts, including inpatients with the e13a3 transcript, which is resistant to TKIs targeting the myristoyl pocket."

Clinical • Chronic Myeloid Leukemia • ABL1

Population Pharmacokinetics of Radotinib in Healthy Volunteers and Patients with Chronic Myeloid Leukemia. (PubMed, Pharmaceuticals (Basel)) - "A 400 mg once-daily regimen was predicted to provide comparable systemic exposures to those of other TKIs with similar physiochemical and pharmacological properties to radotinib, and a 36% lower exposure than that of the current 300 mg twice-daily regimen. The model developed in this study adequately describes the population pharmacokinetics of radotinib and provides a basis for optimal, individualized radotinib therapy for patients with CML."

Journal • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Flumatinib for the Treatment of Adult Patients with Resistant or Intolerant Chronic-Phase Chronic Myeloid Leukemia: Results from Real-World Data (ASH 2023) - "Prior therapies included imatinib, dasatinib, nilotinib, olverembatinib, radotinib and ponatinib. Of the 58 patients, only Grade 1 AEs were reported, including diarrhea, rash and eye edema. Conclusion Flumatinib has good efficacy and safety in the treatment of adult patients with resistant or intolerant Chronic-Phase Chronic Myeloid Leukemia, it will be a good choice for second-line or above treatment for CML-CP In clinical practice."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Improvement of Treatment-Free Remission Rate Following Discontinuation of BCR::ABL1 Tyrosine Kinase Inhibitors in Chronic Phase, Chronic Myeloid Leukemia (ASH 2023) - " Among patients newly diagnosed with CP-CML and treated at least one of TKIs (Imatinib, Nilotinib, Dasatinib, Bosutinib, and Radotinib) as the first treatment, patients who maintained MR4.5 (BCR::ABL1 IS ≤0.0032%) continuously for at least 6 years through qRT-PCR tests were enrolled in this study. Our result demonstrates that TFR rate can be improved in patients who received TKI treatment for approximately 10 years and maintained DMR for more than 6 years regardless of the type of TKI. Based on results, we can confirm one of important factors for safer TFR in CP-CML patients."

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

A More Rapid Initial Decline of BCR::ABL1 Transcripts and Longer Treatment Duration with Improvement of Treatment-Free Remission Rate after Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia (ASH 2024) - "Methods : Among patients newly diagnosed with CP-CML and treated at least one of TKIs (Imatinib, Nilotinib, Dasatinib, Bosutinib, and Radotinib) as the first treatment, patients who maintained MR4.5 (BCR : : ABL1 IS ≤0.0032%) continuously for at least 4 years through reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) tests were enrolled in this study. Conclusion : Our result demonstrates that TFR rate can be improved in patients who received TKI treatment for approximately 10 years and maintained DMR for more than 6 years regardless of the type of TKI. Based on results, we can confirm that a more rapid initial BCR : : ABL1 decline after commencing TKI and total duration of TKI therapy correlated with an increased probability of achieving TFR eligibility."

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

BCR-ABL tyrosine kinase inhibitors associated acute kidney injury: a pharmacovigilance study based on the FAERS database with a case report. (PubMed, BMC Nephrol) - "TKIs, including flumatinib, may cause AKI; however, FAERS-based disproportionality analysis does not indicate an increased renal safety signal compared to non-TKIs. Among TKIs, dasatinib and nilotinib have lower reporting disproportionality than imatinib does, suggesting a potential therapeutic advantage of their use for patients with kidney diseases."

Adverse events • Journal • Acute Kidney Injury • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Nephrology • Oncology • Renal Disease • ABL1 • BCR

Tyrosine kinase inhibitors, nilotinib and radotinib, suppress both catalytic function and mRNA expression of human cytochrome P450 2J2 and 2C8. (PubMed, Drug Metab Pharmacokinet) - "Among the TKIs, nilotinib and radotinib strongly inhibited CYP2J2-dependent astemizole O-demethylation and rivaroxaban hydroxylation, and CYP2C8-mediated paclitaxel 6α-hydroxylation (<20 %), with competitive inhibition constants of 0.41 and 0.22 μM, respectively (for astemizole O-demethylation). Given that their inhibition constants are lower than their reported plasma concentrations, both may substantially suppress CYP2J2 and CYP2C8 functional enzyme levels and enzymatic activities in clinical settings. This suppression could potentially alter vasodilation by affecting 14,15-EET production, influencing CYP2J2 and CYP2C8-mediated drug-disease (conditions) and drug-drug interactions."

Journal • Hematological Malignancies • Leukemia • Oncology

Electric Field-Driven Modulation of Nanomechanical Interactions Between Tyrosine Kinase Inhibitors and Human Serum Albumin: Insights from AFM-Based Force Spectroscopy. (PubMed, Molecules) - "In this study, we investigated how varying electric field strengths (0-100 mV/mm) influence the interfacial interaction between human serum albumin (HSA) and six tyrosine kinase inhibitors (TKIs): imatinib, bosutinib, dasatinib, nilotinib, ponatinib, and radotinib. Notably, more hydrophobic TKIs showed greater responsiveness. These findings highlight the potential of electric fields to modulate protein-drug interactions in a controllable manner, offering a new strategy for the development of electrically tunable drug delivery systems and smart biomedical interfaces."

Journal

In silico repurposing of FDA-approved drugs against MEK1: structural and dynamic insights into lung cancer therapeutics. (PubMed, Front Pharmacol) - "Radotinib and Alectinib exhibited superior docking scores (-10.5 and -10.2 kcal/mol), outperforming the reference MEK1 inhibitor Selumetinib (-7.2 kcal/mol). A limitation of this in silico study is the absence of experimental validation, which will be addressed in future work. Experimental validation is essential to confirm their efficacy and safety in MEK1-linked malignancies."

FDA event • Journal • Lung Cancer • Oncology • Solid Tumor • MAP2K1

Dose Optimization of Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia. (PubMed, Clin Pharmacol) - "This review will classify the dose optimization of all approved TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, asciminib, radotinib) at different stages of treatment based on clinical trials and real-life studies, including dose optimization prior to attempting TFR. In addition, we briefly describe the application of therapeutic drug monitoring in dose optimization and the potential benefits of dose optimization on health-related quality of life."

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

REAL-WORLD TREATMENT PATTERNS OF TYROSINE KINASE INHIBITORS IN KOREAN PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA (EHA 2025) - "Approval of nilotinib and radotinib (2012) for reimbursement in Korea led to a shift in treatment patterns between 2012-2017. These results provide insights on treatment decision-making and choosing the optimal TKI sequence in pts with CML based in Korea, taking into account the unique treatment landscape."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pulmonary Disease • Respiratory Diseases

PATIENTS WITH CHRONIC MYELOID LEUKEMIA WHO HAVE NOT ACHIEVED MAJOR MOLECULAR RESPONSE HAD SIGNIFICANTLY INCREASED RISK OF DISEASE PROGRESSION WHEN RECEIVING DE-ESCALATION TYROSINE KINASE INHIBITORS (TKIS) TREATMENT (EHA 2025) - "The definition of a lower dosage includes: imatinib < 400 mg/d, nilotinib < 600 mg/d, dasatinib < 100 mg/d, flumatinib < 600 mg /d, radotinib < 600 mg /d, asciminib < 80 mg/d. Compared with patients who reduced the maintenance dose of TKI after achieving MMR, patients receiving TKIs with lower dosage before achieving MMR or discontinued TKI treatment before reaching the TFR criteria had significantly increased risk of treatment failure and disease progression."

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

CLINICAL PHARMACOKINETIC CHARACTERISTICS AND THE EXPOSURE-RESPONSE RELATIONSHIP OF RADOTINIB IN ASIAN PATIENTS WITH CHRONIC MYELOID LEUKEMIA (EHA 2025) - "This abstract reports, for the first time, the PK characteristics and the exposure-response relationship of radotinib in patients. The accumulation of radotinib was substantial at the 12-hour dosing interval with the half-life of 25.5 hours, which suggests that the interval should be extended. Ctrough may be used for dose adjustments in CML patients, considering that radotinib exposure was higher in patients with MMR or DLTs."

Clinical • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Hepatology • Leukemia • Oncology • ABL1 • BCR

CLINICAL PHARMACOKINETIC CHARACTERISTICS AND THE EFFECT OF FOOD ON RADOTINIB IN HEALTHY VOLUNTEERS (EHA 2025) - "This is the first study that fully assessed the clinical PK characteristics of radotinib and the food effect in healthy volunteers. Following a single oral dose, the terminal t1/2 of than the dosing interval of 12 hours, suggesting that the dosing interval should be lengthened (e.g., 24 hours). Food intake substantially increases the extent of radotinib absorption."

Clinical • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Clinical Trial to Investigate the Effects of Food on the Pharmacokinetics and Safety of Orally Administered Radotinib (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Il-Yang Pharm. Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion

DASATINIB AS TARGETED THERAPY FOR POST-TRANSPLANT EXTRAMEDULLARY RELAPSE. AN OBSERVATIONAL STUDY (EBMT 2025) - "Among the 159, 70% were receiving, or had received, imatinib when EML presented...Dasatinib interruption resulted in EM relapses in 3; with nilotinib or radotinib, remission was regained... Dasatinib, alone or added to routine treatments, has produced remissions of leukemic involvement of CNS and various organs, some of unusually long duration. This is a significant advance in eradicating EML, where there is no reliably effective therapy. EML remissions were reported in most of 159 cases; including 34 of 35 with EML post-transplant."

Clinical • Observational data • Post-transplantation • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • T Acute Lymphoblastic Leukemia • Transplantation • ABL1 • LCK

DASATINIB AS TARGETED THERAPY FOR POST-TRANSPLANT EXTRAMEDULLARY RELAPSE. AN OBSERVATIONAL STUDY (EBMT 2025) - "Among the 159, 70% were receiving, or had received, imatinib when EML presented...Dasatinib interruption resulted in EM relapses in 3; with nilotinib or radotinib, remission was regained... Dasatinib, alone or added to routine treatments, has produced remissions of leukemic involvement of CNS and various organs, some of unusually long duration. This is a significant advance in eradicating EML, where there is no reliably effective therapy. EML remissions were reported in most of 159 cases; including 34 of 35 with EML post-transplant."

Clinical • Observational data • Post-transplantation • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • T Acute Lymphoblastic Leukemia • Transplantation • ABL1 • LCK

Radotinib-induced Eruptive Melanocytic Naevi in a Patient with Chronic Myeloid Leukaemia. (PubMed, Indian J Dermatol) - No abstract available

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

Chemotherapeutic potential of radotinib against blood and solid tumors: A beacon of hope in drug repurposing. (PubMed, Bioorg Chem) - "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."

Journal • Review • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • CNS Disorders • Hematological Malignancies • Idiopathic Pulmonary Fibrosis • Immunology • Leukemia • Movement Disorders • Multiple Myeloma • Oncology • Parkinson's Disease • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ABL1 • BCR

Repurposed drugs as histone deacetylase 8 inhibitors: Implications in cancer and neuropathological conditions. (PubMed, Front Pharmacol) - "Principal component analysis and Gibbs free energy calculations strongly recommend that both complexes were highly stable during the simulation. Overall, the results indicate that radotinib and sertindole can be promising candidates as HDAC8-targeting repurposed drugs against cancer and neuropathological conditions."

Epigenetic controller • Journal • CNS Disorders • Oncology • HDAC8

A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs (clinicaltrials.gov) - P3 | N=173 | Recruiting | Sponsor: Il-Yang Pharm. Co., Ltd. | Trial completion date: Apr 2025 ➔ Dec 2027 | Trial primary completion date: Jan 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Chronic Myeloid Leukemia • Leukemia • Oncology • ABL1 • BCR

Clinical Trial to Investigate the Effects of Food on the Pharmacokinetics and Safety of Orally Administered Radotinib (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Il-Yang Pharm. Co., Ltd. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

Efficacy and Safety of Dose Redution of Radotinib as a First Line Treament in Ph+ CML (clinicaltrials.gov) - P=N/A | N=168 | Recruiting | Sponsor: Il-Yang Pharm. Co., Ltd.

New trial • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Targeting STAT3, FOXO3a, and Pim-1 kinase by FDA-approved tyrosine kinase inhibitor-Radotinib: An in silico and in vitro approach. (PubMed, Arch Pharm (Weinheim)) - "Two compounds, namely, radotinib and capmatinib, were identified as top compounds using molecular docking. The Western blot analysis assay showed that the phosphorylation level of STAT3 was significantly decreased upon radotinib treatment. Taken together, our findings suggest that radotinib, which is currently used in the treatment of chronic myeloid leukemia (CML), could be considered as a potential candidate for repurposing in the treatment of HCC."

FDA event • Journal • Preclinical • Chronic Myeloid Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Hepatoblastoma • Hepatocellular Cancer • Hepatology • Leukemia • Liver Cancer • Oncology • Solid Tumor • FOXO3 • PIM1 • STAT3

Comparative efficacy and safety of first-line tyrosine kinase inhibitors in chronic myeloid leukemia: a systematic review and network meta-analysis. (PubMed, Transl Cancer Res) - "In terms of efficacy, second-generation TKIs such as dasatinib, nilotinib, and radotinib showed certain advantages in improving patients' MMR and CCyR compared to imatinib...Dasatinib more likely caused anemia, bosutinib thrombocytopenia, and imatinib neutropenia, whereas nilotinib and flumatinib might have better safety profiles in terms of severe hematologic adverse events...Thus, as each second-generation TKI has a distinct clinical efficacy and safety, and is associated with different economic factors, its choice should be dictated by the specific patient clinical conditions (patient's specific disease characteristics, comorbid conditions, potential drug interactions, as well as their adherence). Nevertheless, due to the limited number of original research, additional high-quality studies are needed to achieve any firm conclusion on which second-generation TKI is the best choice for that peculiar patient."

Journal • Retrospective data • Review • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Neutropenia • Oncology • Thrombocytopenia