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Author Notes:

Jorge Cortes, Georgia Cancer Center, Augusta University, 1410 Laney Walker Blvd, CN2222, Augusta, GA 30912; jorge.cortes@augusta.edu

O.P., J.B., and J.S. designed the study and developed the protocol; J.B. developed the statistical plan; S.d.B., P.F., K.Y., C.R., A.H.W., P.M., D.C.T., A.P., T.B., A.C., C.G., B.A.J., A.K., O.L., P.P., M.A., W.B., D.C., D.K.H., J.G.J., J.K., X.T., J.M.W., and J.Y. recruited the patients; S.d.B., P.F., K.Y., C.R., A.H.W., P.M., D.C.T., A.P., T.B., A.C., C.G., B.A.J., A.K., O.L., P.P., M.A., W.B., D.C., D.K.H., J.G.J., J.K., X.T., J.M.W., J.Y., J.C., O.P., J.B., J.S., and E.B. collected the data; O.P., J.B., J.S., and E.B. participated in the analysis and interpretation of pharmacokinetic and pharmacodynamic data; and all authors participated in the analysis and interpretation of the clinical data and the development of the manuscript and were responsible for the decision to submit the article for publication.

Medical writing support was provided by Patrick Barry (Acumen Medical Communications) and was funded by Forma Therapeutics, Inc. This study was funded by Forma Therapeutics, Inc. D.C.T. is supported by the National Institute for Health Research Royal Marsden/Institute of Cancer Research Biomedical Research Centre. The sponsor of this study (Forma Therapeutics, Inc.) collaborated with the clinical investigators in the study design, conduct, and data collection. The study sponsor analyzed the data and conducted the statistical analyses. All authors had access to, and had the opportunity to review, the study data.

S.d.B. has received honoraria and research funding from Forma Therapeutics; has received honoraria and research funding from and is a consultant to Agios; has received honoraria from, is a consultant to, and is on the speakers’ bureau for Celgene; has received honoraria from and is a consult to Astellas, Daiichi Sankyo, Syros, AbbVie, Bayer, and Janssen; has received honoraria from Seattle Genetics; and is a consultant to Pierre Fabre, Novartis, Pfizer, and Servier. P.F. is a consultant to and has received honoraria and research funding from AbbVie, Janssen, Jazz Pharmaceuticals, Novartis, and Bristol Myers Squibb (BMS). K.Y. is a consultant to and has received research funding from F. Hoffman-La-Roche and Jazz Pharmaceticals; is a consultant to and has received honoraria and research funding from Novartis; is a consultant to Astellas, BMS/Celgene, GlaxoSmithKline, Pfizer, Shattuck Labs, Taiho, and Takeda; has received research funding from Astex, Forma Therapeutics, Geron, Gilead, Janssen, Karyopharm, and Treadwell; and has received honoraria from AbbVie. C.R. is a consultant to, has received honoraria and research funding from, and is a board/advisory committee member for AbbVie, BMS, and Jazz Pharmaceuticals; has received honoraria and research funding from and is a board/advisory committee member for Amgen and Astellas; is a board/advisory committee member for Novartis, Pfizer, and Takeda; and is a consultant to, has received honoraria from, and is a board/advisory committee member for Servier. A.H.W. has received honoraria and research funding from, is a consultant to, is on the speakers’ bureau, and is a board/advisory committee member for Astellas; has received honoraria and research funding from, is on the speakers’ bureau, and is a board/advisory committee member for AbbVie/Genentech, Amgen, Celgene/BMS, and Novartis; has received research funding and honoraria from, is a consultant to, and is a board/advisory committee member for Servier and Syndax; has received honoraria from, is a consultant to, and is a board/advisory committee member for Janssen and Gilead; has received honoraria from and is a board/advisory committee member for MacroGenetics and Pfizer; has received honoraria and research funding from and is a board/advisory committee member for AstraZeneca; has received research funding from Astex; is an employee of the Walter and Eliza Hall Institute; and is eligible for a fraction of the royalty stream related to venetoclax. P.M. is a consultant to, has received research funding from, and is on the speakers’ bureau for AbbVie, BMS, and Pfizer; is a consultant to and has received research funding from Menarini/Stemline, Novartis, and Takeda; is a consultant to and is on the speakers’ bureau for Jazz Pharmaceuticals and Astellas; and is a consultant to Otsuka, Kura Oncology, BeiGene, Incyte, Ryvu, and Nerviano. D.C.T. has received research funding from Bayer and from AbbVie to attend the American Society of Hematology meeting. A.P. has received honoraria from and is a consultant to AbbVie; is a consultant to Gilead; and has received honoraria from Astellas, Agios, Pfizer, and Jazz Pharmaceuticals. A.C. is a board/advisory committee member for Jazz Pharmaceuticals, Pfizer, Novartis, and AbbVie. C.G. is a board/advisory committee member for Astellas, AbbVie, and Otsuka; has received honoraria for her institution for participation in advisory boards for Astellas, AbbVie, and Otsuka, and for chairing an educational meeting for AbbVie. B.A.J. has received research funding for his institution, is a consultant to, and is a board/advisory committee member for, AbbVie, BMS, Genentech/F. Hoffman-La-Roche, Jazz Pharmaceuticals, Pfizer, and Treadwell; has received research funding for his institution, is a consultant to, and is a data monitoring committee member for Gilead; has received research funding for his institution, is a consultant to, and is a protocol steering committee member for GlycoMimetics; is a consultant to and a board/advisory committee member for Rigel, Servier, Takeda, and Tolero; has received travel reimbursement/expenses from AbbVie and Rigel; has received research funding for his institution from 47, Accelerated Medical Diagnostics, Amgen, Arog, Celgene, Daiichi Sankyo, F. Hoffman-La-Roche, Forma Therapeutics, Hanmi, Immune-Onc, Incyte, Loxo Oncology, LP Therapeutics, Pharmacyclics, and Sigma Tau. P.P. is a board/advisory committee member for Jazz Pharmaceuticals, Astellas, Celgene, and AbbVie. M.A. is a consultant to and a board/advisory committee member for BMS/Celgene and Novartis; and is a consultant to Astellas, Jazz Pharmaceuticals, and Pfizer. W.B. is a board/advisory committee member for Syndax; has received research funding from Xencor and Celyad; and has received honoraria from AmerisourceBergen. D.K.H. has received research funding from Novartis. J.G.J. is a consultant to, a board/advisory committee member for, and has received research funding from AbbVie, Daiichi Sankyo, and Celgene; is a consultant to, and a board/advisory committee member for Novartis; and has received research funding from Arog Pharmaceuticals, Astellas, Forma Therapeutics, Genentech, Kura Oncology, PTC Therapeutics, and Syros Pharmaceuticals. J.M.W. has received research funding from and is a board/advisory committee member for Takeda; has received research funding from Immune System Key Ltd and Takeda; and is a board/advisory committee member for Genentech, Rafael Pharma, Reven Pharma, and Celgene/BMS. J.Y. has received research funding from Seattle Genetics, Janssen, Arog, Loxo Oncology, and Agios. O.P., J.B., J.S., and E.B. are employees of and hold stock in Forma Therapeutics. J.C. has received research funding for his institution from and is a consultant to AbbVie, BMS, Novartis, Pfizer, Takeda, Daiichi, Jazz Pharmaceuticals, Merus, and Forma Therapeutics; has received research funding for his institution from Astellas and Amphivena; and is a consultant to Gilead, BioLineRx, and BioPath. The remaining authors declare no competing financial interests.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • MUTATIONS
  • LEUKEMIA

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML

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Journal Title:

BLOOD ADVANCES

Volume:

Volume 7, Number 13

Publisher:

, Pages 3117-3127

Type of Work:

Article | Final Publisher PDF

Abstract:

Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). Overall, 153 IDH1 inhibitor–naive patients with mIDH1R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) received olutasidenib monotherapy 150 mg twice daily in the pivotal cohort of this study. The median age of participants was 71 years (range, 32-87 years) and the median number of prior regimens received by patients was 2 (1-7). The rate of complete remission (CR) plus CR with partial hematologic recovery (CRh) was 35%, and the overall response rate was 48%. Response rates were similar in patients who had, and who had not, received prior venetoclax. With 55% of patients censored at the time of data cut-off, the median duration of CR/CRh was 25.9 months. The median duration of overall response was 11.7 months, and the median overall survival was 11.6 months. Of 86 patients who were transfusion dependent at baseline, a 56-day transfusion independence was achieved in 29 (34%), which included patients in all response groups. Grade 3 or 4 treatment-emergent adverse events (≥10%) were febrile neutropenia and anemia (n = 31; 20% each), thrombocytopenia (n = 25; 16%), and neutropenia (n = 20; 13%). Differentiation syndrome adverse events of special interest occurred in 22 (14%) patients, with 14 (9%) grade ≥3 and 1 fatal case reported. Overall, olutasidenib induced durable remissions and transfusion independence with a well-characterized and manageable side effect profile. The observed efficacy represents a therapeutic advance in this molecularly defined, poor-prognostic population of patients with mIDH1 R/R AML.

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© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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