Forma Therapeutics to Present Data from Pivotal Phase 2 Trial of Olutasidenib at ASCO 2021
Olutasidenib demonstrated a 33.3% composite complete remission rate (CR/CRh) in people living with R/R AML with the IDH1 mutation
Among those with CR/CRh, estimated 18-month survival is 87%; median overall survival has not yet been reached
Duration of response of 13.8 months is longest reported in this treatment setting to date
Favorable tolerability profile following continuous oral treatment with olutasidenib 150mg BID
The presentation is based on an interim analysis from a pivotal trial arm evaluating continuous treatment with 150 mg twice daily of oral olutasidenib. The data indicate the duration of CR/CRh for people on treatment was 13.8 months. Among patients with a complete remission (CR) who were transfusion-dependent at baseline, 56-day transfusion independence was achieved in 100% of patients as measured by platelets and 83% as measured by red blood cells.
“The data being presented at ASCO showcase olutasidenib’s meaningful progress for this patient population, which currently has limited options to extend life expectancy,” said
Oral Abstract Session –
- Abstract #7006: Effect of olutasidenib (FT-2102) on complete remissions in patients with relapsed/refractory (R/R) mIDH1 acute myeloid leukemia (AML): Results from a planned interim analysis of a phase 2 clinical trial
About the Phase 1/2 Study
The Phase 1/2 study is a multicenter, open-label, multi-cohort evaluation of the safety, efficacy and pharmacokinetics/pharmacodynamics (PK/PD) of olutasidenib for patients with AML or myelodysplastic syndrome (MDS) with an IDH1 mutation. Phase 1 of the trial, 2102-HEM-101, was an open-label, dose-escalation and expansion study of olutasidenib alone and in combination with azacitidine (AZA). The Phase 2 portion was an open-label, fixed-dose study of olutasidenib as a monotherapy and in combination with AZA in multiple IDH1m AML/MDS populations. The primary efficacy evaluable population is comprised of 123 R/R AML patients enrolled in Cohort 1, who received 150 mg of olutasidenib BID at least six months prior to the interim analysis cutoff date of
Key Study Findings
Olutasidenib induced a durable CR/CRh rate of 33.3% (95% CI 25.1, 42.2), which is the primary endpoint of the study:
- The CR rate was 30.0% (37 of 123 patients) and the CRh rate was 3.0% (4 of 123 patients)
- While the median duration of response was not yet reached, in a sensitivity analysis with hematopoietic stem cell transplant considered as the end of a response, the median duration was 13.8 months.
- The median duration of overall response was 11.7 months.
- The median overall survival (OS) was 10.5 months. The median OS for non-CR/CRh responders was 15.0 months. A median OS has not yet been reached for the CR/CRh population, with an 18-month survival estimate of 87.0%.
- Transfusion independence was achieved in all response groups at 56 days, particularly in those achieving CR, with 100% independence for platelet transfusions and 83.0% independence for red blood cells.
Olutasidenib was well-tolerated, with adverse events (AEs) consistent with the late stage disease and the heavily pre-treated population. A safety analysis for all 153 patients enrolled in the Phase 2 Cohort 1 found the most common grade 3/4 (≥ 20% or ≥ 10%) treatment-emergent adverse events (TEAEs) were febrile neutropenia (20%), anemia (19%), thrombocytopenia (16%), neutropenia (13%), leukocytosis (9%) and fatigue (<1%). AEs of interest were the following:
- 14% of patients reported AEs due to Differentiation syndrome, including 7% Grade 3 and 1% Grade 4 AEs. Most resolved with corticosteroids and treatment interruption. However, 1 fatal event was reported.
- 8% of patients reported AEs due to QTc prolongation, with <1% Grade 3 or 4. No events led to discontinuation.
- Grade 3 or 4 elevation in liver parameters (ALT/AST/total bilirubin) occurred in 10% and 2% of patients, respectively. Most resolved with treatment interruption and dose reduction. Seven patients (<5%) discontinued study treatment due to LFT abnormalities. No Hy’s law cases reported.
Olutasidenib is an oral, potent, 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. With the conclusion of the Phase 2 R/R AML trial, Forma has begun preparing a new drug application (NDA) for submission to the
IDH1 is a natural enzyme that is part of the normal metabolism of all cells; when mutated, its activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6-8% of patients with AML and as many as 70 to 80% of patients with grade II/III gliomas and secondary glioblastoma. In gliomas, IDH1 mutations occur early in the tumor pathogenesis and persist throughout progression from a neural stem or progenitor cell. Gliomas are the most common, aggressive and difficult-to-treat primary brain tumors, and high-grade gliomas are associated with poor long-term prognosis. Treatment options for relapsed glioma are limited.
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 our beliefs and expectations regarding: interim data analysis for olutasidenib in the Phase 2 trial in R/R AML; the therapeutic potential and clinical benefits and safety related to olutasidenib; whether interim results from our clinical trials are predictive of final trial results or future clinical studies; our planned presentation of data at ASCO; and planned regulatory submissions, including the preparation and submission of an NDA for olutasidenib with the FDA. 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 related our ability to execute on our strategy; the finalization of our Phase 2 study in R/R AML and final audit and quality controlled verification of interim data and related analyses; positive results from interim data analyses may not be predictive of final results; risks related to our planned regulatory submissions and developments; and other risks identified in our