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1514 Time to Response and Overall Survival in Patients with mIDH1 Relapsed/Refractory Acute Myeloid Leukemia Treated with Olutasidenib

Program: Oral and Poster Abstracts
Session: 617. Acute Myeloid Leukemias: Commercially Available Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Acute Myeloid Malignancies, AML, Adult, Clinical Research, Chemotherapy, Genetic Disorders, Diseases, Treatment Considerations, Non-Biological therapies, Myeloid Malignancies, Study Population, Human
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Eunice S. Wang, MD1, Jorge E. Cortes, MD2, Justin M. Watts, MD3, Brian A. Jonas, MD, PhD4, Andrew H Wei, MBBS, PhD, FRACP, FRCPA5, Jay Yang, MD6, Joseph G Jurcic, MD7, Gail J. Roboz, MD8, Karen Seiter, MD9, Alice Mims, MD10, Karen Yee, MD, FRCPC11*, P. Brent Ferrell, MD12, Shira N. Dinner, MD13, William B. Donnellan, MD14, William Blum, MD15, Francois Di Trapani16*, Hua Tian16* and Stephane De Botton, MD, PhD17*

1Leukemia Service, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
2Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA
3Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL
4Department of Internal Medicine, Division of Malignant Hematology/Cellular Therapy and Transplantation, University of California Davis School of Medicine, Sacramento, CA
5Department of Haematology, The Alfred Hospital, Melbourne, VIC, Australia
6Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI
7Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY
8Weill Cornell Medicine and The New York Presbyterian Hospital in New York City, New York, NY
9New York Medical College, Valhalla, NY
10The Ohio State University Comprehensive Cancer Center, Columbus, OH
11Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
12Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
13Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
14Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN
15Emory University, Winship Cancer Institute, Atlanta, GA
16Rigel Pharmaceuticals, Inc., South San Francisco, CA
17Department of Hematology, Institut Gustave Roussy, Villejuif, France

Introduction: Up to 16% of patients with acute myeloid leukemia (AML) have a mutation in the isocitrate dehydrogenase 1 gene (mIDH1), which acts as an oncogenic driver of underlying leukemic disease. Inhibitors of mIDH1 provide therapeutic benefits. Olutasidenib, a potent and selective oral small-molecule mIDH1 inhibitor, selectively binds and inhibits both single and double-mutated IDH1 variants while retaining wild-type IDH1 function. In the registrational phase 2 trial (NCT02719574), olutasidenib demonstrated an overall response in 48% of patients with relapsed/refractory (R/R) AML; the median time to response was 1.9 months with a range of 0.9 to 10.2 months. The objective of this analysis was to evaluate whether time to response (TTR) impacted outcomes including overall survival (OS) in patients treated on this olutasidenib phase 2 trial.

Methods: The pivotal cohort of this open-label, multicenter, registrational, global phase 2 trial enrolled adult patients (≥18 years of age) with mIDH1 R/R AML. Patients received 150 mg olutasidenib twice daily. The primary endpoint was complete remission (CR) plus CR with partial hematologic recovery (CRh) using criteria from the International Working Group in AML. Secondary endpoints included overall response rate (ORR), which was defined as CR + CRh + CR with incomplete blood count recovery (CRi), partial remission (PR), and morphologic leukemia-free state (MLFS); time to first response (TTFR); time to best response (TTBR); duration of response (DOR); and OS. Data cut-off was June 2023.

Results: This analysis included 147 efficacy evaluable patients with up to five years of follow-up. The primary endpoint of CR/CRh was achieved by 35% (51/147) of patients. In these 51 patients with CR/CRh, the median TTBR was 1.9 months, and median OS was not reached (NR; 95%CI: 22.8, NR; range 6.3-57.1). TTBR was 0.9–1.9 months in 28/51 (55%) patients, with median OS of NR (95%CI: 38.1, NR). TTBR was 2.1–4.0 months in 17/51 (33%) patients, with median OS of 20.3 months (95%CI: 14.7, NR). TTBR was 4.6–5.6 months in 6/51 (12%) patients, with median OS of NR (95%CI: 19.4, NR).

Among the 71 (48%) patients achieving an overall response, median TTFR was 1.9 months; median OS was 32.7 months (95%CI: 20.1, NR) and maximum OS was 57.1+ months. TTFR was 0.9–1 month in 23/71 (32%) patients, with median OS of NR (95%CI: 19.0, NR). TTFR was 1.1–1.9 months in 24/71 (34%) patients, with median OS of 22.9 months (95%CI: 12.5, NR). TTFR was 2.1 to 3.8 months in 17/71 (24%) patients, with median OS of 20.1 months (95%CI: 10.2, 31.3). TTFR was 4.6 to 10.2 months in 7/71 (10%) patients, with median OS of NR (95%CI: 23.9, NR). A Cox regression model showed no significant association between TTR and OS in the overall responders and those with a CR/CRh response.

Among the 20 other responders (not CR/CRh), median TTFR was 1.9 months (range 0.9-10.2) and median survival was 13.7 months (95%CI: 6.0, 28.3). TTFR was <2.0 months in 12/20 other responders, with median survival of 11.3 months (95%CI: 4.4, NR). In the 8 other responders with TTFR >2.0 months, the median survival was 19.4 months (95%CI: 6.0, 31.3).

Conclusions: These results show that while some patients with mIDH1 R/R AML achieve response to olutasidenib very quickly, other patients who continue treatment with olutasidenib achieve response at later timepoints, after up to 6 months of treatment for CR/CRh and 10 months for an overall response. These results support the prescribing information that suggests treating for at least 6 months to allow time for clinical response in patients without disease progression or unacceptable toxicity. Time to response was not associated with overall survival in the overall responders and those with a CR/CRh (Cox Model).

Disclosures: Wang: UptoDate: Other: Section Editor; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sumitomo Pharma: Membership on an entity's Board of Directors or advisory committees; Mana: Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; J&J: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Speakers Bureau; Sellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Blueprint: Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Speakers Bureau; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Kura: Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Membership on an entity's Board of Directors or advisory committees; Qiagen: Membership on an entity's Board of Directors or advisory committees; Schrodinger: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Immunogen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; NuProbe: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Committee, Award Committee, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Committee, Research Funding, Speakers Bureau. Cortes: Rigel: Consultancy; Biopath Holdings: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy; Ascentage: Research Funding; Pfizer: Consultancy; Lilly: Consultancy; Nerviano: Consultancy; Novartis: Consultancy, Research Funding; AbbVie: Research Funding; Sun Pharma: Consultancy, Research Funding. Watts: Celgene/BMS: Consultancy; Takeda: Research Funding; Immune Systems Key: Research Funding; Rafael Pharma: Consultancy; Reven Pharma: Consultancy; Daiichi Sankyo: Consultancy; Aptose: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Other: safety monitoring or advisory boards, Research Funding. Jonas: Celgene: Research Funding; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptose: Research Funding; Amgen: Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Other: Travel; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlycoMimetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AROG: Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kymera: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman-La Roche: Research Funding; Forma Therapeutics: Research Funding; Forty-Seven: Research Funding; Hanmi: Research Funding; Immune-Onc: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Loxo Oncology: Research Funding; Pharmacyclics: Research Funding; Sigma Tau: Research Funding; Treadwell: Research Funding. Wei: AbbVie Inc, Astellas, Bristol Myers Squibb, Novartis, Servier Pharmaceuticals LLC: Speakers Bureau; Servier Pharmaceuticals LLC, Shoreline Biosciences: Consultancy; AbbVie Inc, Amgen Inc, Astex Pharmaceuticals, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Janssen Biotech Inc, Novartis, Servier Pharmaceuticals LLC, Syndax Pharmaceuticals: Research Funding; AbbVie Inc, Agios Pharmaceuticals Inc, Amgen Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Gilead Sciences Inc, Janssen Biotech Inc, MacroGenics Inc, Novartis, Pfizer Inc, Roche Laboratories Inc, Servier Pharmaceuticals LLC, Shoreli: Membership on an entity's Board of Directors or advisory committees. Yang: Pfizer: Research Funding; Novartis: Consultancy, Research Funding; Puretech: Research Funding. Jurcic: Sumitomo Pharma: Research Funding; Pfizer: Research Funding; Rigel Pharmaceuticals: Consultancy; BMS/Celgene: Research Funding; Forma Therapeutics: Research Funding; Blueprint Medicines: Research Funding; Gallop Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Syros Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Roboz: Novartis, Pfizer, Roche, GlaxoSmithKline, BMS, Syndax, Rigel: Consultancy; AbbVie, Amgen, Astrazeneca, Caribou Biosciences, Celgene, Daiichi Sankyo, Ellipses pharma, Geron, GSK, Glycomimetics, Janssen, Jasper Pharmaceuticals, Jazz Pharmaceuticals, Molecular Partners, Oncoverity: Consultancy; Janssen: Research Funding; OncoPrecision: Current holder of stock options in a privately-held company, Honoraria. Seiter: Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Rafael: Research Funding; Glycomimetics: Research Funding; Celgene: Research Funding. Mims: Leukemia and Lymphoma Society Beat AML Study: Other: Senior Medical Director; Novartis: Membership on an entity's Board of Directors or advisory committees; Treadwell Therapeutics: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Membership on an entity's Board of Directors or advisory committees; Daiichi Saynko: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Yee: Astex: Other: research support; Forma Therapeutics: Other: research support; F. Hoffmann-La Roche: Other: research support; Genentech: Other: research support; Geron: Other: research support; Gilead Sciences: Other: research support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: research support; Bristol Myers Squibb/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Taiho Pharma: Membership on an entity's Board of Directors or advisory committees; Taiho Pharma: Honoraria. Ferrell: Novartis: Research Funding. Dinner: Rigel: Consultancy; Pfizer: Consultancy; Kite: Consultancy. Di Trapani: Rigel: Current Employment, Current equity holder in private company. Tian: Rigel: Current Employment. De Botton: Jazz Pharmaceuticals: Speakers Bureau; Astellas: Speakers Bureau; AbbVie: Other: travel, Speakers Bureau; Syndax: Consultancy; Servier: Consultancy, Other: travel, Speakers Bureau; Remix: Consultancy; GlaxoSmithKline: Consultancy; Forma: Research Funding; Auron: Research Funding; BMS: Consultancy, Speakers Bureau; Loxo: Honoraria.

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