Pharmacokinetics of asciminib in the presence of CYP3A or P‐gp inhibitors, CYP3A inducers, and acid‐reducing agents

Autor: Matthias Hoch, Felix Huth, Masahiko Sato, Tirtha Sengupta, Michelle Quinlan, Stephanie Dodd, Shruti Kapoor, Florence Hourcade‐Potelleret

Publikováno v: Clinical and Translational Science, Vol 15, Iss 7, Pp 1698-1712 (2022)

Abstract Asciminib is a first‐in‐class inhibitor of BCR::ABL1, specifically targeting the ABL myristoyl pocket. Asciminib is a substrate of CYP3A4 and P‐glycoprotein (P‐gp) and possesses pH‐dependent solubility in aqueous solution. This rep

Externí odkaz: https://doaj.org/article/5df116dd14d544be888ed9ac77e9a8fa

Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results

Autor: Michael J. Mauro, Timothy P. Hughes, Dong-Wook Kim, Delphine Rea, Jorge E. Cortes, Andreas Hochhaus, Koji Sasaki, Massimo Breccia, Moshe Talpaz, Oliver Ottmann, Hironobu Minami, Yeow Tee Goh, Daniel J. DeAngelo, Michael C. Heinrich, Valle Gómez-García de Soria, Philipp le Coutre, Francois-Xavier Mahon, Jeroen J. W. M. Janssen, Michael Deininger, Naranie Shanmuganathan, Mark B. Geyer, Silvia Cacciatore, Fotis Polydoros, Nithya Agrawal, Matthias Hoch, Fabian Lang

Publikováno v: Mauro, M J, Hughes, T P, Kim, D-W, Rea, D, Cortes, J E, Hochhaus, A, Sasaki, K, Breccia, M, Talpaz, M, Ottmann, O, Minami, H, Goh, Y T, DeAngelo, D J, Heinrich, M C, Gómez-García de Soria, V, le Coutre, P, Mahon, F-X, Janssen, J J W M, Deininger, M, Shanmuganathan, N, Geyer, M B, Cacciatore, S, Polydoros, F, Agrawal, N, Hoch, M & Lang, F 2023, ' Asciminib monotherapy in patients with CML-CP without BCR : :ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results ', Leukemia, vol. 37, no. 5, pp. 1048-1059 . https://doi.org/10.1038/s41375-023-01860-w
Leukemia, 37(5), 1048-1059. Nature Publishing Group

Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-lab

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::437d3c00079171293194868f1b37fa7b
https://research.vumc.nl/en/publications/6d526334-4128-4e79-a87b-30d3fb304c73

Population Pharmacokinetics of Asciminib in Tyrosine Kinase Inhibitor-Treated Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic and Acute Phases

Autor: Ying Fei Li, Francois Pierre Combes, Matthias Hoch, Sebastien Lorenzo, Sherwin K. B. Sy, Yu-Yun Ho

Publikováno v: Clinical Pharmacokinetics. 61:1393-1403

Asciminib, a first-in-class, highly potent and specific ABL/BCR-ABL1 inhibitor, has shown superior efficacy compared to bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase, treated with two or more ty

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::17bed89727c5912c6920e1ecba3fee5f
https://doi.org/10.1007/s40262-022-01148-9

Figure S2A and S2B: Geometric mean plasma concentration-time profiles of AZD9496 metabolites M3 (A and B) and M5 (C and D) following a single dose and multiple doses of AZD9496 (n = 3-5 subjects) from A First-in-Human Study of the New Oral Selective Estrogen Receptor Degrader AZD9496 for ER+/HER2− Advanced Breast Cancer

Autor: Seock-Ah Im, Hazel M. Weir, Gaia Schiavon, Shethah R. Morgan, Justin P.O. Lindemann, Teresa Klinowska, Matthias Hoch, Komal Jhaveri, Richard D. Baird, Anne C. Armstrong, Manish R. Patel, Erika P. Hamilton

GAZD9496 metabolite, M3 (Panel A) and M5 (Panel C), geometric mean plasma concentration following a single dose of AZD9496 on Day 1 (semi-log scale). AZD9496 metabolite, M3 (Panel B) and M5 (Panel D), geometric mean plasma concentration following mul

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba39b2e702e6c26c29e1ff3e592e7e25
https://doi.org/10.1158/1078-0432.22464387

Data from Circulating Biomarkers and Resistance to Endocrine Therapy in Metastatic Breast Cancers: Correlative Results from AZD9496 Oral SERD Phase I Trial

Autor: Daniel F. Hayes, Richard Baird, J. Carl Barrett, Elizabeth A. Harrington, Caroline Dive, Fouziah Butt, Nadia Iqbal, Seock-Ah Im, Komal Jhaveri, Anne Armstrong, Manish Patel, Erika Hamilton, Kimberly Aung, Nitharsan Sathiyayogan, Vicky Rowlands, Parul Patel, Shethah Morgan, Gayle Marshall, Justin Lindemann, Teresa Klinowska, Matthias Hoch, Joseph Geradts, T. Hedley Carr, Elizabeth P. Darga, Emily M. Dolce, Gaia Schiavon, Costanza Paoletti

Purpose:Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)–positive metastatic breast cancers include, among others, ER loss and acquired activating mutations in the ligand-binding domain of the ER gene (ESR1LBDm). ESR

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::32d19b6ff53bf7d9bdb2da2810051c15
https://doi.org/10.1158/1078-0432.c.6527325.v1