Forma Therapeutics’ Investigational Olutasidenib in Combination with Azacitidine Yields Durable Complete Remission in Patients with mIDH1 Acute Myeloid Leukemia
First Phase 2 combination trial results presented in oral session at 2021 ASH Annual Meeting
Olutasidenib with azacitidine well tolerated with a safety profile largely consistent with olutasidenib alone
Molecular characteristics of olutasidenib monotherapy response reported in ASH poster presentation
These positive findings, the first Phase 2 results of olutasidenib used in combination with a chemotherapy, were presented in an oral session on
“AML is a cancer that returns in about half of patients following initial treatment. Patients who are not achieving remission or suffer from an AML relapse are in need of new therapies with more durable outcomes. The data presented today at ASH increase our understanding of olutasidenib’s potential to achieve durable complete responses when used as either first-line or second-line therapy along with a standard therapy for patients with mIDH1 AML,” said
The oral presentation reports an analysis of four patient cohorts from the pivotal open-label Phase 2 arm of an ongoing Phase 1/2 study, (2102-HEM-101, NCT02719574), who received olutasidenib dosed 150 milligrams (mg) twice daily continuously during 28-day cycles plus azacitidine, as of
Investigators enrolled patients into one of the four groups based on their disease status and prior therapy and recorded the best overall response for the primary endpoint of a composite complete remission (CR) plus CR with partial hematologic recovery (CRh) rate (CR/CRh). The group of patients who had not yet received therapy for their AML and were candidates for azacitidine as a first-line treatment had CR/CRh rate of 45% (5 out of 11). The other three groups enrolled patients who had relapsed/refractory AML (R/R AML) that, respectively, had prior HMA therapy; had prior therapy with an IDH1 inhibitor, including olutasidenib monotherapy; and were candidates for azacitidine as a first-line treatment. The CR/CRh rates for these groups were 38% (5 of 13), 30% (6 of 20), and 47% (9 of 19), respectively.
Olutasidenib with Azacitidine Well Tolerated
Olutasidenib was well tolerated in the trial in combination with azacitidine and the combination had a safety profile largely consistent with that of olutasidenib alone. Treatment-emergent adverse events (TEAEs) occurring in 25 percent or more of the participants included nausea (49 percent), constipation (40 percent), vomiting (35 percent), thrombocytopenia (32 percent), diarrhea (28 percent), and neutropenia (26 percent). TEAEs of grade 3 or 4 in more than 10 percent of participants included neutropenia (26 percent), thrombocytopenia (25 percent), anemia (19 percent), and febrile neutropenia (14 percent). TEAEs of QTc prolongation occurred in five participants (7 percent), of whom two experienced grade 3 QTc prolongation, and none discontinued olutasidenib.
TEAEs associated with liver enzyme abnormalities occurred in 15 participants (21 percent), with grade 3/4 in six (8 percent). Investigator-assessed IDH1 differentiation syndrome in six (8 percent) patients, of whom most resolved with treatment interruption, dexamethasone, and/or supportive treatment, while two patients had concomitant leukocytosis.
Molecular Characteristics of Response to Olutasidenib in Patients with R/R AML
A poster presentation reported findings from a planned interim analysis of the trial’s cohort of patients with R/R AML receiving olutasidenib alone, dosed 150 mg twice daily. The analysis examined expression of IDH1m variant allele frequency, prevalence of other genetic co-mutations in the trial’s pivotal cohort, and associations between mutations and response. Responses were observed across all IDH1 mutation subtypes and response rates were lower amongst patients with concurrent FLT3 co-mutations. Patients with higher co-mutations at baseline had lower rates of response than those with low mutational burden. Similarly, patients with lower baseline IDH1 expression were more likely to respond than those with high expression.
Olutasidenib Presentations Details
Abstract 698: Olutasidenib (FT-2102) in Combination with Azacitidine Induces Durable
Complete Remissions in Patients with mIDH1 Acute Myeloid Leukemia
Session 616 on
Monday, Dec. 13, at 3:00 PM ET
Jorge E. Cortes, M.D.
Abstract 2351: Molecular Characteristics of Response to Olutasidenib (FT-2102) in Patients with
Relapsed/Refractory mIDH1 Acute Myeloid Leukemia
Session: 616 on
Sunday, Dec. 12, at 6:00 PM ET
Stéphane de Botton, M.D., Ph.D.
For more information, please visit https://www.formatherapeutics.com/clinical-trials/ or https://clinicaltrials.gov/ct2/show/NCT02719574.
Acute myeloid leukemia (AML) is a cancer that starts in a person’s bone marrow but often quickly moves into the blood. AML develops from immature blood cells, known as myeloid cells, that are supposed to mature into white blood cells. However, the diseased myeloid cells do not function properly. They instead multiply rapidly, which causes normal blood cell production to fail. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The
Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.2 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.3
Olutasidenib is an oral, potent and small molecule investigational agent designed to selectively bind to and inhibit mutated IDH1 enzymes. This targeted treatment has the potential to provide therapeutic benefit by reducing 2-HG levels and restoring normal cellular differentiation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. When mutated, IDH1 activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6 to 8 percent of patients with AML.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the company’s beliefs and expectations regarding its: business plans and objectives; future plans for olutasidenib, including expectations regarding timing, success and data announcements of our current clinical trials; therapeutic potential, clinical benefits, molecular characteristics, mechanisms of action and safety of olutasidenib; planned regulatory submissions; and the potential impact of COVID-19 on patient retention and enrollment, future operations, clinical trials or planned regulatory submissions for olutasidenib. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties associated with the following: the impact of the COVID-19 pandemic on the company’s business, operations, patient enrollment and retention, strategy, goals and anticipated milestones; the therapeutic potential of olutasidenib; the timing and completion of our ongoing Phase 1/2 clinical study in olutasidenib; our ability to execute on our strategy for olutasidenib; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; any one or more of our product candidates may not be successfully developed and commercialized; regulatory developments in
American Cancer Society. Key statistics for acute myeloid leukemia (AML). Revised January 12, 2021. Accessed Dec. 2, 2021at https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html.
Leukaemia Care. (2019). Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed
October 2021. Accessed Dec 2, 2021at https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Myeloid-Leukaemia-AML-Web-Version.pdf.
Thol F, Schlenk RF, Heuser M,
Ganser A. HowI treat refractory and early relapsed acute myeloid leukemia. Blood. 2015 Jul 16;126(3):319-27. doi: 10.1182/blood-2014-10-551911. Epub 2015 Apr 7. PMID: 25852056.