MorphoSys AG announced that preliminary results from the ongoing Phase 1/2 study (NCT04104776) of tulmimetostat (CPI-0209) monotherapy in heavily pretreated patients with advanced cancers showed responses or disease stabilization in five cohorts with evaluable patients. Tulmimetostat is an oral, investigational next-generation selective dual inhibitor of EZH2 and EZH1 designed to improve on first generation EZH2 inhibitors via increased potency, longer residence time on target and a longer half-life. The data were presented during poster sessions at the 34th Symposium on Molecular Targets and Cancer Therapeutics hosted by the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR) in Barcelona, Spain.

At data cutoff (July 16, 2022), 51 of 52 patients enrolled in the Phase 2 expansion phase of the trial had received at least one dose of tulmimetostat in the following cohorts:metastatic castration-resistant prostate cancer, lymphoma, BAP1-mutated mesothelioma, ARID1A-mutated ovarian clear cell carcinoma, ARID1A-mutated endometrial carcinoma and ARID1A-mutated urothelial and other metastatic solid tumors. At trial entry, 68% of patients had been treated with at least three prior lines of therapy. Patients received oral tulmimetostat 350 mg once daily.

Of the 10 evaluable patients with ovarian clear cell carcinoma, four had a partial response and three had stable disease. Of the eight evaluable patients with metastatic castration-resistant prostate cancer, five had stable disease. Of the four evaluable patients with endometrial carcinoma, two had partial responses, one of whom later achieved a complete response after data cutoff, and two had stable disease.

Two of the three evaluable patients with peripheral T-cell lymphoma had complete responses. For the nine evaluable patients with mesothelioma, there were two partial responses and four disease stabilizations. The safety profile of tulmimetostat was consistent with the mechanism of action of EZH2 inhibition.

The most frequent treatment-emergent adverse events (AEs) determined to be possibly related to tulmimetostat included thrombocytopenia (47.1%), diarrhea (37.3%), nausea (29.4%), anemia (27.5%), fatigue (25.5%), neutropenia (17.6%), dysgeusia (17.6%), alopecia (15.7%) and vomiting (15.7%). Treatment-emergent AEs led to dose reductions in 16 patients (31.4%) and to dose interruptions in 33 patients (64.7%). Seven patients (13.7%) discontinued treatment due to AEs.