Results from a First-in-Human Phase I Study of Siremadlin (HDM201) in Patients with Advanced Wild-Type TP53 Solid Tumors and Acute Leukemia

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Results from a First-in-Human Phase I Study of Siremadlin (HDM201) in Patients with Advanced Wild-Type TP53 Solid Tumors and Acute Leukemia
 
Stein, Eytan M; DeAngelo, Daniel J; Chromik, Jörg; Chatterjee, Manik; Bauer, Sebastian; Lin, Chia-Chi; Suarez, Cristina; De Vos, Filip; Steeghs, Neeltje; Cassier, Phillippe A; Tai, David; Kiladjian, Jean-Jacques; Yamamoto, Noboru; Mous, Rogier; Esteve, Jordi; Minami, Hironobu; Ferretti, Stéphane; Guerreiro, Nelson; Meille, Christophe; Radhakrishnan, Rajkumar; Pereira, Bernard; Mariconti, Luisa; Halilovic, Ensar; Fabre, Claire; Carpio, Cecilia
(2022) Clinical cancer research : an official journal of the American Association for Cancer Research, volume 28, issue 5, pp. 870 - 881
(Article)
Abstract
Purpose: This phase I, dose-escalation study investigated the recommended dose for expansion (RDE) of siremadlin, a p53- MDM2inhibitor, in patients with wild-type TP53 advanced solid or hematologic cancers. Patients and Methods: Initial dosing regimens were: 1A (day 1; 21-day cycle; dose 12.5-350 mg) and 2A (days 1-14; 28-day cycle; dose ... read more
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Keywords: Oncology, Cancer Research, Journal Article
DOI: https://doi.org/10.1158/1078-0432.CCR-21-1295
ISSN: 1078-0432
Publisher: American Association for Cancer Research Inc.
Note: Funding Information: Sankyo, Roche, Exelixis, Bayer, and Pharmamar; grants and personal fees from Blueprint Medicines; and grants from Incyte outside the submitted work. C.-C. Lin reports personal fees from BeiGene, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, PharmaEngine, Roche, and AbbVie outside the submitted work. C. Suarez reports grants from AB Science, Aragon Pharmaceuticals and AstraZeneca AB, Blueprint Medicines Corporation, Boehringer Ingelheim España, S.A., Clovis Oncology, Exelixis Inc, F., Genentech Inc, GlaxoSmithKline, S.A, and Novartis Farmacéutica, S.A.; grants and personal fees from Astellas Pharma, Bayer, Bristol Myers Squibb (Inst), Hoffmann-La Roche LTD, Pfizer S.L.U, and Sanofi-Aventis; and personal fees from Eusa Pharma, Ipsen, Merck Sharp & Dohme Corp., and Novartis outside the submitted work. F. de Vos reports research funding to institution from AbbVie, BioClin Therapeutics, Bristol Myers Squibb, GlaxoSmithKline, Novartis, Octimet Oncology, and VAXIMM. F. de Vos received funding for expert testimony form Bristol Myers Squibb, as well as travel and accommodations from Roche/Genentech. N. Steeghs reports multiple grants to institution (Netherlands Cancer Institute) during the conduct of the study and outside the submitted work. P.A. Cassier reports other support from Novartis during the conduct of the study. P.A. Cassier also reports other support from AbbVie, Adlai Nortye, Alligator, Bayer, BMS, Boston, Exelixis, GSK, Innate Pharma, Iteos, Janssen, Lilly/Loxo, Molecular Partners, OSE, Roche/Genetech, Sotio, Taiho, Toray, Transgene, and MSD; personal fees and other support from Amgen; non-financial support from AstraZeneca; non-financial support and other support from Debio; personal fees from EMD Serono; and grants and other support from Novartis outside the submitted work. D. Tai reports grants from BMS, Sirtex, and Novartis outside the submitted work. J.-J. Kiladjian reports personal fees from Novartis during the conduct of the study, as well as personal fees from AbbVie and BMS outside the submitted work. N. Yamamoto reports grants from Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO, Janssen Pharma, MSD, Merck, GSK, Sumitomo Dainippon, Chiome Bioscience, Otsuka, Carna Biosciences, and Genmab, as well as personal fees from Eisai, Takeda, Otsuka, Boehringer Ingelheim, Cimic, and Chugai outside the submitted work. J. Esteve reports personal fees from AbbVie, Jazz Pharmaceuticals, Novartis, Astellas, Bristol Myers Squibb–Celgene, and Novartis outside the submitted work. H. Minami reports grants from Novartis during the conduct of the study. H. Minami also reports grants from Astellas, Boehringer, Merck Serono, CSL Behring, Nihon Kayaku, Shionogi, Nihon Shinyaku, and Mitsubishi Tanabe Pharma; other support from AstraZeneca; grants, personal fees, and other support from Bayer, Bristol Myers Squibb, Chugai, Daiichi Sankyo, MSD, and Ono Pharmaceutical; grants and personal fees from DaiNihonSumitomo, Eizai, Kyowa-Kirin, Sanofi, Takeda, Taiho, and Lilly; personal fees from Celgene, Ohtsuka, Genomic Health, AbbVie, and Amgen; and personal fees and other support from Pfizer outside the submitted work. S. Ferretti reports other support from Novartis outside the submitted work. C. Meille reports personal fees from Novartis during the conduct of the study, as well as personal fees from Novartis outside the submitted work. B. Pereira reports nonfinancial support from ArticulateScience during the conduct of the study, as well as other support from Novartis outside the submitted work; B. Pereira is a full-time employee of Novartis. L. Mariconti reports personal fees from Novartis during the conduct of the study, as well as personal fees from Novartis outside the submitted work. E. Halilovic reports to be an employee and a stockholder of Novartis. C. Fabre reports other support from Novartis during the conduct of the study, as well as other Funding Information: The authors would like to thank the patients who participated in this study, along with their families. The authors also thank Matthieu Klopfenstein, Audrey Kaag, Astrid Jullion, Anil Gaur, Sebastian Szpakowski, Swann Gaulis, Arun Kumar, and Jens Wuerthner for their contributions to the study. Ram Reddy Kanthala is thanked for leading the programming activities for the study. This study was sponsored by Novartis Pharmaceuticals Corporation. Medical writing assistance was provided by Zoe Crossman, PhD, of ArticulateScience, and was funded by Novartis Pharmaceuticals Corporation. Publisher Copyright: © 2021 The Authors.
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