Tulmimetostat

Tulmimetostat (CPI-0209) is an investigational next-generation dual inhibitor of Enhancer of Zeste Homolog 2 (EZH2) and EZH1 designed to counter abnormal gene activity that may contribute to cancer development and progression, as well as drug resistance.

In September 2023, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for tulmimetostat for the treatment of patients with advanced, recurrent or metastatic endometrial cancer harboring AT-rich interacting domain containing protein 1A (ARID1A) mutations and who have progressed on at least one prior line of treatment.
 

Tulmimetostat is an Investigational Next-Generation EZH2/EZH1 Dual Inhibitor

Tulmimetostat is a once-daily oral therapy developed to inhibit the epigenetic regulators EZH2 and EZH1, with the aim of restoring normal gene expression. Tulmimetostat was designed to improve on first-generation EZH2 inhibitors through increased potency, longer residence time on target and a longer half-life, offering the potential for enhanced anti-tumor activity. 

In a Phase 1/2 clinical study, tulmimetostat has shown preliminary anti-tumor activity in heavily pre-treated patients across solid tumors and lymphomas. An interim review of safety data suggests that the safety profile of tulmimetostat is consistent with EZH2 inhibitor class effects and with previous data; further study is warranted and ongoing.
 

Abnormal EZH2 and EZH1 Activity Promotes Cancer Development

EZH2 and EZH1 are proteins involved in the regulation of genes controlling cell division and cell death. Deviations in EZH2 activity can cause the atypical expression of these genes, which in turn can contribute to tumor development, growth and progression. 

Patients with EZH2-mutated or overexpressing cancers often face poor prognoses. Furthermore, increases in EZH2 activity can contribute to the ability of cancer cells to develop resistance to therapies. If EZH2 is inhibited as part of targeted cancer therapies, EZH1 may compensate for EZH2 activity. Dual inhibition of EZH2 and EZH1 may have the potential to overcome current treatment limitations and improve outcomes for patients.

Phase 1/2 Trial 

Study Description

Tulmimetostat is being investigated in a first-in-human, open-label sequential dose escalation and expansion Phase 1/2 study (NCT04104776) in patients with advanced solid tumors and lymphomas, including ARID1A-mutated endometrial carcinoma and ovarian clear cell carcinoma, diffuse large B-cell lymphoma, peripheral T-cell lymphoma, BAP1-mutated mesothelioma and metastatic castration-resistant prostate cancer.
 

Endpoints

The primary endpoints are frequency of dose-limiting toxicities (to determine the maximum tolerated dose and/or recommended Phase 2 dose) and overall response rate (to evaluate efficacy). Key secondary endpoints include additional efficacy assessments such as progression-free survival, overall survival, disease control rate, time to response, and duration of response, safety assessments such as adverse events and change in laboratory values, and pharmokinetic assessments such as area under the curve versus time and maximum observed plasma concentration (C_max).

Tulmimetostat is an investigational agent; its safety and efficacy have not been established. Tulmimetostat is currently not approved by regulatory authorities for the treatment of any disease anywhere in the world. It cannot be prescribed or purchased for therapy at present. The MorphoSys website may contain information on drug candidates and clinical trials sponsored by MorphoSys with the intention of increasing the transparency of the company’s clinical research. There is no guarantee any product will be approved in the sought-after indication. Information contained within this website is not intended to replace the advice of a healthcare professional and should not be considered as a recommendation. Patients should always seek medical advice before making any decisions on their treatment. All reasonable precautions have been taken to ensure the accuracy, security, and confidentiality of information available through the site. MorphoSys may amend the information at any time without notice.