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

Excerpt from the Press Release:

WATERTOWN, Mass.–(BUSINESS WIRE)–Dec. 16, 2021– Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX), a clinical-stage biopharmaceutical company focused on sickle cell disease, prostate cancer and other rare hematologic diseases and cancers, today announced the company’s investigational oral, selective mIDH1 inhibitor combined with azacitidine yielded durable complete remission (CR) or CR with partial hematologic recovery (CRh) responses with favorable tolerability in patients with the mIDH1 form of acute myeloid leukemia (AML).

These positive findings, the first Phase 2 results of olutasidenib used in combination with a chemotherapy, were presented in an oral session on Dec. 13, 2021, at the 63rd American Society of Hematology (ASH) Annual Meeting. The findings support the potential of olutasidenib as the basis of combination therapy in patients with AML who have not achieved a durable response from prior therapy. In addition, a poster, presented on Dec. 12 at ASH, reported on the molecular characteristics of the mIDH1 of patients in the trial who responded to olutasidenib when administered as monotherapy.

“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 Patrick Kelly, M.D., chief medical officer of Forma Therapeutics.

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 June 16, 2021. Azacitidine, a hypomethylating agent (HMA), was administered daily as an intravenous or subcutaneous injection therapy for days one to seven of each cycle.

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
  Presenter: 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
  Presenter: 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.

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