MorphoSys AG (MOR) announces preliminary results of the phase 1/2 study of tulmimetostat (CPI-0209)

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

“These early data support further investigation of the broad therapeutic potential of tulmimetostat in heavily pretreated patients with advanced cancers,” said Charles Drescher, MD, gynecologic oncologist and medical director of gynecologic cancer research at the Institute. Swedish Cancer Center in Seattle, Washington. “Patients with advanced cancer who have progressed after previous treatments have significant treatment needs that could benefit from a targeted approach with an EZH2 inhibitor. We look forward to learning more as we go along.” as the trial progresses.”

As of the data cut-off date (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-clear cell carcinoma of the mutated ovary, ARID1A– mutated endometrial carcinoma and ARID1A– mutated urothelial tumors and other metastatic solid tumours. At the start of the trial, 68% of patients had been treated with at least three prior lines of treatment. Patients received 350 mg of tulmimetostat orally once daily.

Of the 10 evaluable patients with clear cell carcinoma of the ovary, 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 subsequently achieved a complete response after data cutoff, and two had stable disease. Two of 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 stabilizations of the disease.

The safety profile of tulmimetostat was consistent with the mechanism of action of EZH2 inhibition. The most common treatment-emergent adverse events (AEs) deemed 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 dose interruptions in 33 patients (64.7%). Seven patients (13.7%) discontinued treatment due to AE.

“Tulmimetostat was designed to target both EZH2-related tumor progression and redundant actions of EZH1 with high potency and durability, along with additional pharmacokinetic advances over prior EZH2 inhibitors, offering the potential to increased antitumor activity in many cancer types,” said Tim Demuth, MD, Ph.D., director of research and development at MorphoSys. “Preliminary data from the ongoing Phase 2 trial showing antitumor activity in multiple cancers supports our aspiration to discover the full potential of EZH2 inhibition. These results are an important step towards demonstrating proof-of-concept, as we continue to study multiple-dose tulmimetostat to identify the optimal efficacy-safety profile.”

Also presented were updated results from the Phase 1 dose escalation trial, in which 41 patients were treated with oral tulmimetostat ranging from 50 mg to 375 mg daily. At the start of the study, 15 patients had ARID1A alterations across multiple tumor types, and all mesothelioma patients had BAP1 alterations. Dose-limiting thrombocytopenia grade 4 toxicity was observed, which occurred at the highest dose. The disease control rate (complete and partial responses + disease stabilization) at 375 mg was 66.7%. Disease control was noted at all doses except 137.5 mg. Three of the six patients in the 100 mg cohort had stable disease. Of the seven patients in the 225 mg cohort, four had disease stabilization and one with BAP-1 mutated mesothelioma had a partial response. Another partial response was noted in ARID1A-mutated endometrial carcinoma at 375 mg. These early results support patient selection based on ARID1A and BAP1 in the ongoing Phase 2 expansion study.

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