Curis announced preliminary tolerability and PK data from its ongoing Phase 1 dose-finding study of fimepinostat, a small molecule dual inhibitor of PI3K/HDAC and suppressor of MYC, in combination with venetoclax, a BCL-2 inhibitor, for the treatment of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), including patients with double-hit/double-expressor (DH/DE) lymphoma.

"We are very pleased with the progress in our ongoing Phase 1 study, with the combination of fimepinostat and venetoclax demonstrating a favorable tolerability profile thus far," said James Dentzer, President and Chief Executive Officer of Curis. "We believe demonstrating that this combination is generally well-tolerated for patients is a significant milestone, as both drugs have shown activity as monotherapies in this patient population and we believe activity will be improved by combining the two agents. Based on these data, we plan to initiate an expansion of the current study in 2020."

To date, the study has enrolled 11 patients, 6 patients in the first cohort and 5 patients in the second cohort. Patients in the first cohort received 30mg once-daily (QD) of fimepinostat and 400mg QD of venetoclax, while the patients in the second cohort received 60mg QD of fimepinostat and 400mg QD of venetoclax. To date the combination has been generally well-tolerated by patients.

"There is an urgent need for therapies targeting MYC and BCL-2 alterations, particularly in DH/DE lymphoma, a disease defined by these alterations and one of the deadliest types of lymphoma," said Robert Martell, M.D, Ph.D, Head of R&D at Curis. "We believe fimepinostat is unique in its ability to target MYC through simultaneous inhibition of both PI3K and HDAC. Venetoclax is a rapidly-acting inhibitor of BCL2, the other key abnormality in DH lymphoma. Supported by synergistic anti-cancer effects observed in preclinical models, we believe this is an ideal combination to target DLBCL and we look forward to gaining further insights on the combination from this study.

"The study was designed with initial patients undergoing a several-week run-in period allowing detailed PK interaction analysis and venetoclax ramp-up to be performed," Dr. Martell said. "In preliminary analyses, we found the combination to be generally well tolerated, with no dose-limiting toxicity (DLT) in the first cohort and one DLT of transient grade 3 diarrhea in the second cohort. Importantly, we found no drug-drug PK interaction that required dose modification of either agent. Drug-drug interactions are a major problem for many drugs combining with venetoclax, and we are encouraged that we have not seen such interaction to date with fimepinostat."

Curis' ongoing Phase 1, open-label, multi-center, dose-finding 3+3 study is designed to evaluate the safety and tolerability, PK and pharmacodynamics, and preliminary activity of the fimepinostat and venetoclax combination in patients with DLBCL, including those with DH/DE lymphoma. Patients are enrolled in two cohorts in the study, with fimepinostat administered on a 5-days-on-2-days-off schedule in combination with venetoclax in 21-day cycles. Curis plans to initiate an expansion of the current study in 2020.

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