Supect (radotinib)

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.

P1, N=24, Active, not recruiting, Il-Yang Pharm. Co., Ltd. | Not yet recruiting --> Active, not recruiting

P=N/A, N=168, Recruiting, Il-Yang Pharm. Co., Ltd.

P3, N=173, Recruiting, Il-Yang Pharm. Co., Ltd. | Trial completion date: Apr 2025 --> Dec 2027 | Trial primary completion date: Jan 2025 --> Jun 2026

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.

P2, N=40, Recruiting, Il-Yang Pharm. Co., Ltd. | Trial completion date: May 2025 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2025

P1, N=24, Not yet recruiting, Il-Yang Pharm. Co., Ltd.

Our findings highlighted the potential of Nilotinib and Radotinib as promising candidates against HCK that offer valuable insights into their binding mechanisms. This computational approach provides a comprehensive understanding of drug interactions with HCK and sets the stage for future experimental validation and drug development endeavors.Communicated by Ramaswamy H. Sarma.

P3, N=238, Active, not recruiting, Il-Yang Pharm. Co., Ltd. | Trial completion date: Dec 2023 --> Jun 2025

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.

Newer BCR-ABL TKIs provide superior cancer outcomes but with increased risk of acute arterial thrombosis, which further increases in patients with cardiovascular comorbidities and mitigates survival benefits compared to imatinib...Of the new agents, bafetinib decreased EC viability and increased microvessel permeability while asciminib and radotinib did not impact any EC function tested. In summary, the vasculotoxic TKIs (dasatinib, ponatinib, nilotinib) cause EC toxicity but with mechanistic differences, supporting the potential need for drug-specific vasculoprotective strategies. Asciminib and radotinib do not induce EC toxicity at clinically relevant concentrations suggesting a better safety profile.

The following terms were searched: (Leukemia, Myelogenous, Chronic and BCR-ABL Positive), chronic myeloid leukemia, tyrosine kinase inhibitor, TKI, imatinib, dasatinib, nilotinib, bosutinib, and radotinib. In conclusion, our findings suggest that cutaneous adverse events occur more frequently with second-generation TKIs than with imatinib. Therefore, effective management of the cutaneous outcome is necessary to achieve high patient adherence to medication and successful treatment with TKIs.

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.

Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood-brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.

Background: In ASCEMBL, after ≥2 y of follow-up, asciminib (ASC) continued to demonstrate superior efficacy and better safety and tolerability than bosutinib (BOS), with more pts on ASC remaining on and continuing to benefit from therapy over time... Eligible pts with intolerance or treatment failure/lack of efficacy per European LeukemiaNet (ELN) 2013 recommendations were randomized 2:1 to ASC 40 mg twice daily or BOS 500 mg once daily and gave informed consent...Overall MMR rates at wk 96 were higher with ASC than BOS regardless of the last prior TKI received (imatinib, 55.6% vs 14.3%; nilotinib, 40.9% vs 35.7%; dasatinib, 37.1% vs 10.5%; radotinib, 50.0% vs 0%; ponatinib, 20.0% vs 11.8%) and reason for its discontinuation (intolerance [ASC, n=59; BOS, n=22] vs resistance [ASC, n=95; BOS, n=54])... Responses were fast with ASC and continued to deepen over time. Pts who remained on ASC beyond wk 24 could still achieve MMR by later time points. Overall MMR rates at wk 96 were higher with ASC than BOS regardless of the last TKI and reason for its discontinuation; MMR rates were also higher with ASC in pts resistant to all prior 2G TKIs.

Treatment agents such as tyrosine kinase inhibitors (Imatinib, Dasatinib, Nilotinib, Bosutinib, Ponatinib, Radotinib), Omacetaxine and Asciminib have been used in the treatment of Bcr abl positive CML according to the patient's clinic and mutation status. All patients responded well to imatinib therapy. During follow up patients who maintained their MMR achieve had a better clinical course and prognosis compared to other CML patients.

Furthermore, radotinib significantly suppressed MM cell growth in a xenograft animal model using IM-9 cells. In conclusion, radotinib may play an important role as a candidate agent for MM treatment.

P3, N=173, Recruiting, Il-Yang Pharm. Co., Ltd. | Trial completion date: Apr 2023 --> Apr 2025 | Trial primary completion date: Mar 2022 --> Jan 2025

P3, N=238, Active, not recruiting, Il-Yang Pharm. Co., Ltd. | Recruiting --> Active, not recruiting

In addition, radotinib significantly suppressed MM cell growth in a xenograft animal model using RPMI-8226 cells, and killed ex vivo myeloma cells from patients. In conclusion, radotinib may play an important role as a candidate agent or chemosensitizer for the treatment of MM.

No abstract available

Safety profiles were consistent with previous reports; most adverse events occurred within 12 months. Radotinib continues to demonstrate robust, deep molecular responses, suggesting that treatment-free remission may be attainable.

Therefore, our results can be concluded that radotinib in combination with Ara-C possesses a strong anti-AML activity.

Out of 56 patients with molecular relapse, 54 patients (except two patients who restart radotinib) were re-treated with IM, all patients (except one patient lost follow-up) re-achieved MMR at a median of 1.9 months (range, 0.0 - 5.4 months) after resuming treatment. Among them, two patients who re-achieving of MMR after resuming IM therapy lost MMR again; One patient who relapsed at 53.2 months after IM discontinuation, despite re-achieving MMR 1.4 later after IM restarting, suddenly progressed to blast crisis at 6 months after restarting IM and in spite of switching to dasatinib and ponatinib, she died...In addition, we demonstrated that a second attempt might be possible. Further studies on the predictors to select patients for a trial of second stop are warranted.