- |||||||||| Kinaction (masitinib) / AB Science
Journal: 'Piperazining' the catalytic gatekeepers: unraveling the pan-inhibition of SRC kinases; LYN, FYN and BLK by masitinib. (Pubmed Central) - Jul 21, 2020
Molecular dynamics simulations revealed initial selective targeting of catalytic residues (Asp334/Glu335 - LYN, Asp130/Asp148/Glu54 - FYN, Asp89 - BLK) by masitinib, with high-affinity interactions via its piperazine ring at the entrance of the ATP-binding pockets, before systematic access into the hydrophobic deep pocket grooves. Identification of these 'gatekeeper' residues could open up a novel paradigm of structure-based design of highly selective pan-inhibitors of BCR signaling in the treatment of diffuse large B-cell lymphoma.
- |||||||||| Kinaction (masitinib) / AB Science
Clinical, Journal: Prospective clinical trial of masitinib mesylate treatment for advanced stage III and IV canine malignant melanoma. (Pubmed Central) - Jul 3, 2020
Masitinib, a first-in-class tyrosine kinase inhibitor targeting mast cell activity in severe asthma patients, demonstrated a positive benefit/risk ratio over a sustained period and may provide a new treatment option in severe asthma, irrespective of baseline eosinophil level. There was only mild effectiveness in end-stage disease, indicating that masitinib mesylate is not an appropriate sole-agent option for treatment of advanced malignant melanoma in dogs.
- |||||||||| Kinaction (masitinib) / AB Science
[VIRTUAL] Efficacy and safety of masitinib in severe asthma: Eosinophilic subgroup analysis from study AB07015 () - May 19, 2020 - Abstract #EAACI2020EAACI_685;
P3
The primary analysis of study AB07015 was positive, with an acceptable safety profile, for uncontrolled severe asthma irrespective of eosinophil levels. Masitinib also shows significant improvement in severe eosinophilic (150 cells/L) asthma and may therefore provide a new treatment option for biologic-ineligible pts (e.g. eosinophil count of 300 cells/L) or pts in failure to biologics.
- |||||||||| Kinaction (masitinib) / AB Science, tadalafil / Generic mfg.
Preclinical, Journal: Effects of masitinib compared with tadalafil for the treatment of monocrotaline-induced pulmonary arterial hypertension in rats. (Pubmed Central) - May 19, 2020
Masitinib, a tyrosine kinase inhibitor appears safer and more potent than imatinib for treatment of malignancies, but its efficacy on PAH is unknown...Collectively, these results suggest that the treatment with a low-dose masitinib was non-inferior than tadalafil. A lower dose of masitinib may represent a novel approach to target both the cardiopulmonary remodeling and the dysregulated vasoconstriction in PAH.
- |||||||||| Review, Journal, Adverse events: Potential use of edaravone to reduce specific side effects of chemo-, radio- and immuno-therapy of cancers. (Pubmed Central) - Apr 19, 2020
EDA is a mild antiproliferative agent but has been found to enhance significantly the anticancer and antimetastatic activities of irinotecan in a colon cancer model...Notably EDA can reduce the renal dysfunction induced by cisplatin, the neurotoxicity of cyclophosphamide and the cardiotoxicity of doxorubicin...Therefore, EDA could also be useful to reduce specific side effects of immuno-therapy. Collectively, the information suggests that the medical use of EDA, a drug with a proven safety after 18 years of use in brain-related Human diseases, could be extended to cancer-related conditions.
- |||||||||| Kinaction (masitinib) / AB Science
Trial primary completion date: Efficacy and Safety of Masitinib in the Treatment of Progressive Multiple Sclerosis (clinicaltrials.gov) - Apr 8, 2020
P3, N=656, Completed,
Collectively, the information suggests that the medical use of EDA, a drug with a proven safety after 18 years of use in brain-related Human diseases, could be extended to cancer-related conditions. Trial primary completion date: Feb 2020 --> Sep 2019
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date: Masitinib in Patients With Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - Apr 7, 2020
P3, N=721, Active, not recruiting,
Trial primary completion date: Feb 2020 --> Sep 2019 Trial completion date: Sep 2020 --> Jun 2020 | Trial primary completion date: Sep 2020 --> Dec 2019
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Stroma: Masitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib (clinicaltrials.gov) - Apr 6, 2020
P3, N=258, Active, not recruiting,
Trial completion date: Sep 2020 --> Jun 2020 | Trial primary completion date: Sep 2020 --> Dec 2019 Trial completion date: Dec 2020 --> Jun 2020 | Trial primary completion date: Dec 2020 --> Jun 2020
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Combination therapy: Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients (clinicaltrials.gov) - Apr 6, 2020
P3, N=495, Not yet recruiting,
Trial completion date: Dec 2020 --> Jun 2020 | Trial primary completion date: Dec 2020 --> Jun 2020 Trial completion date: Dec 2023 --> Sep 2022 | Trial primary completion date: Dec 2022 --> Jun 2022
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Masitinib in Combination With Gemcitabine in Advanced/Metastatic Epithelial Ovarian Cancer Patients (clinicaltrials.gov) - Apr 6, 2020
P2/3, N=248, Active, not recruiting,
Trial completion date: Dec 2023 --> Sep 2022 | Trial primary completion date: Dec 2022 --> Jun 2022 Trial completion date: Dec 2020 --> Jun 2020 | Trial primary completion date: Dec 2020 --> Jun 2020
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Combination therapy, Metastases: AB12005: Masitinib Plus Gemcitabine in Pancreatic Cancer (clinicaltrials.gov) - Apr 6, 2020
P3, N=377, Active, not recruiting,
Trial completion date: Dec 2020 --> Jun 2020 | Trial primary completion date: Sep 2020 --> Dec 2019 Trial completion date: Dec 2020 --> Sep 2020 | Trial primary completion date: Dec 2020 --> Sep 2020
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Masitinib Plus Docetaxel in Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - Apr 6, 2020
P3, N=580, Recruiting,
Trial completion date: Dec 2020 --> Sep 2020 | Trial primary completion date: Dec 2020 --> Sep 2020 Trial completion date: Mar 2021 --> Dec 2020 | Trial primary completion date: Mar 2021 --> Dec 2020
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion, Trial completion date, Trial primary completion date: Efficacy and Safety of Masitinib in the Treatment of Progressive Multiple Sclerosis (clinicaltrials.gov) - Apr 3, 2020
P3, N=656, Completed,
Active, not recruiting --> Completed | Trial completion date: Jun 2020 --> Nov 2019 Active, not recruiting --> Completed | Trial completion date: Sep 2020 --> Feb 2020 | Trial primary completion date: Sep 2019 --> Feb 2020
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Combination therapy: Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients (clinicaltrials.gov) - Apr 3, 2020
P3, N=495, Not yet recruiting,
Active, not recruiting --> Completed | Trial completion date: Sep 2020 --> Feb 2020 | Trial primary completion date: Sep 2019 --> Feb 2020 Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Jun 2022 --> Dec 2022
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Combination therapy: Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients (clinicaltrials.gov) - Apr 2, 2020
P3, N=495, Not yet recruiting,
Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Jun 2022 --> Dec 2022 Trial completion date: Nov 2024 --> Jun 2023 | Trial primary completion date: Nov 2021 --> Jun 2022
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date: Masitinib in Patients With Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - Apr 1, 2020
P3, N=721, Active, not recruiting,
Trial completion date: Nov 2024 --> Jun 2023 | Trial primary completion date: Nov 2021 --> Jun 2022 Trial completion date: Dec 2019 --> Sep 2020 | Trial primary completion date: Dec 2019 --> Sep 2020
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Stroma: Masitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib (clinicaltrials.gov) - Apr 1, 2020
P3, N=258, Active, not recruiting,
Trial completion date: Dec 2019 --> Sep 2020 | Trial primary completion date: Dec 2019 --> Sep 2020 Trial completion date: Dec 2022 --> Dec 2020 | Trial primary completion date: Dec 2021 --> Dec 2020
- |||||||||| Kinaction (masitinib) / AB Science
Trial primary completion date, Combination therapy, Metastases: AB12005: Masitinib Plus Gemcitabine in Pancreatic Cancer (clinicaltrials.gov) - Apr 1, 2020
P3, N=377, Active, not recruiting,
Trial primary completion date: Dec 2019 --> Sep 2020 Trial primary completion date: Jun 2020 --> Dec 2020
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Masitinib Plus Docetaxel in Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - Apr 1, 2020
P3, N=580, Recruiting,
Trial primary completion date: Jun 2020 --> Dec 2020 Trial completion date: Sep 2020 --> Mar 2021 | Trial primary completion date: Mar 2020 --> Mar 2021
- |||||||||| Kinaction (masitinib) / AB Science
Preclinical, Journal: Flavone-based arylamides as potential anticancers: Design, synthesis and in vitro cell-based/cell-free evaluations. (Pubmed Central) - Mar 12, 2020
Two compounds 2aw and 2ax emerged as effective, broad-spectrum and potent anticancer agents that outperformed masitinibt and imatininb, which are FDA-approved anticancer drugs...Mechanistic study showed that compounds 2aw triggers cell cycle arrest in HT29 colon cancer cells. In conclusion, this work presents compound 2aw as a new broad-spectrum anticancer agent for further development of promising treatment of diverse cancers.
- |||||||||| Kinaction (masitinib) / AB Science
Journal: Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS. (Pubmed Central) - Dec 21, 2019
Postparalysis treatment of SOD1G93A rats with the tyrosine kinase inhibitor drug masitinib prevented mast cell and neutrophil infiltration, axonal pathology, secondary demyelination, and the loss of type 2B myofibers, compared with vehicle-treated rats. These findings provide further evidence for a yet unrecognized contribution of immune cells in peripheral motor pathway degeneration that can be therapeutically targeted by tyrosine kinase inhibitors.
- |||||||||| Kinaction (masitinib) / AB Science
Trial primary completion date: Masitinib in Treatment of Patients With Severe Persistent Asthma Treated With Oral Corticosteroids (clinicaltrials.gov) - Dec 3, 2019
P3, N=420, Active, not recruiting,
These findings provide further evidence for a yet unrecognized contribution of immune cells in peripheral motor pathway degeneration that can be therapeutically targeted by tyrosine kinase inhibitors. Trial primary completion date: Jun 2019 --> Nov 2019
- |||||||||| Kinaction (masitinib) / AB Science
Trial completion date, Trial primary completion date, Combination therapy: Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients (clinicaltrials.gov) - Dec 2, 2019
P3, N=495, Not yet recruiting,
Trial completion date: Dec 2020 --> Aug 2019 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2019 --> Aug 2019; Sponsor decision based on portfolio prioritization Trial completion date: May 2024 --> Nov 2024 | Trial primary completion date: May 2021 --> Nov 2021
- |||||||||| Kinaction (masitinib) / AB Science
Journal: An evaluation of masitinib for treating systemic mastocytosis. (Pubmed Central) - Nov 27, 2019
Expert opinion: In spite of their similarity in chemistry and biological activity against submolecular targets, masitinib is much more selective towards c-kit receptors than other tyrosine kinases, such as Bcl-Abl. Furthermore, its ability to inhibit degranulation, cytokine production and MCs migration from bone marrow gives it a great chance to become an important therapeutic option for selected SM patients.
- |||||||||| Zydelig (idelalisib) / Gilead
Secreted Factors Determine Resistance to Idelalisib in Marginal Zone Lymphoma Models of Resistance (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3739;
Recombinant HBEGF also induced resistance to the BTK inhibitor ibrutinib in the PAR cells and in the mantle cell lymphoma SP-53 cell line...We identified treatments that might overcome resistance to idelalisib and are worth of further investigations . The two models, driven by different biologic processes, will allow the evaluation of further alternative therapeutic approaches.
- |||||||||| Tasigna (nilotinib) / Novartis, Inhibikase
Long-Term Response to Nilotinib in GIST (Gastrointestinal Stromal Tumor): A Case Report of the Resistance Mutation pY823D in Exon 17 of the Kit Gene (M3) - Sep 30, 2019 - Abstract #DGHO2019DGHO_799;
Masatinib first line treatment was started within the AB04030 study...Molecular diagnostics revealed a secondary KIT mutation in Exon 17 (pY823D) which is known to procure resistance to the tyrosine kinase inhibitors Imatinib and Sunitinib in vitro...Subsequent therapies comprised the established tyrosine kinase inhibitors Sunitinib for three months and fourth-line Regorafenib for nine months, eventually resulting in progressive disease...No relevant adverse events were reported by the meanwhile 81 years old patient who is still under therapy with Nilotinib. Collectively, the presented case can be seen as a powerful example of rationally applied molecularly targeted therapies and, to our knowledge, represents the first case report of a durable therapy response to Nilotinib for GIST harboring the pY823D resistance mutation in KIT Exon 17.
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