Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating innovative personalized therapeutics for patients with genetically defined cancers, announced today the presentation of results from the company’s Phase 1 trial of EPZ-5676, a potent and selective inhibitor of the DOT1L histone methyltransferase (HMT). Epizyme, along with its partner Celgene, is developing EPZ-5676 for the treatment of acute leukemia with alterations in the MLL gene (MLL-r) or partial tandem duplications within MLL (MLL-PTD). The trial found that EPZ-5676 was generally safe and well tolerated across all dose cohorts and showed clinical and biological activity. These data will be presented today by Eytan M. Stein, M.D., Memorial Sloan Kettering Cancer Center, at the 56th annual meeting of the American Society of Hematology (ASH) in San Francisco, Calif.
Forty-two heavily pre-treated acute leukemia patients were enrolled and evaluable for anti-leukemic activity as of the data cut-off of October 6, 2014. Thirty-four of these patients had MLL-r or MLL-PTD.
- Eight of the 34 MLL-r or MLL-PTD patients across all dose levels, and nine patients overall, showed biological or clinical activity
- Two of five MLL-r patients enrolled in the 54 mg/m2/day dose cohort achieved CRs (one morphologic CR and one cytogenetic CR); one patient of 23 enrolled in the 90 mg/m2/day dose cohort achieved a PR
- The two patients with CRs had MLL-r with an (11;19) translocation, and the patient with the PR had a trisomy 11, which is associated with MLL-PTD
- Two patients, including one with CR, experienced resolution of leukemia cutis, and eight patients experienced leukemia cell differentiation characterized by morphological maturation or non-malignant leukocytosis
“In this heavily pre-treated patient population, there is a significant unmet need,” said Dr. Stein. “MLL-r acute leukemias are particularly difficult to treat, and the safety profile and clinical and biological activity we have seen with EPZ-5676, including two complete responses, are encouraging.”
“We are pleased to have seen objective responses as well as resolution of leukemia cutis and differentiation effects among patients in this study,” said Peter Ho, M.D., Ph.D., Chief Development Officer, Epizyme. “Based on the clinical activity we observed at intermediate dose cohorts, we plan to enroll up to 20 additional MLL-r or MLL-PTD patients at 54 mg/m2/day to explore further the single agent activity of EPZ-5676 at this dose and to better characterize the molecular profile of responding patients.”
The objectives of this Phase 1, open-label, dose escalation study are to determine the maximum tolerated dose or recommended Phase 2 dose, and to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-leukemic activity of EPZ-5676 in adult patients with relapsed/refractory leukemia, including those with MLL-r or MLL-PTD.
Thirty-one percent of patients had one prior therapy, 31 percent had two prior therapies, 24 percent had three prior therapies, and 14 percent had four or more prior therapies. Thirty-eight percent of patients had received prior allogeneic hematopoietic cell transplant.
Adverse events assessed by investigators to be drug-related were seen in 38 percent of patients. The majority were Grade 1 or Grade 2 gastrointestinal events. Three patients experienced Grade 3 leukocytosis, and one patient experienced Grade 3 anemia. Two dose-limiting toxicities occurred at 90 mg/m2/day: one Grade 4 reversible cardiac failure with concurrent sepsis and one Grade 4 reversible hypophosphatemia.
Pharmacokinetic and pharmacodynamic data were consistent with results reported by the Company in its November 6, 2014 press release.