FDA Grants Fast Track Designation to Tulmimetostat for Endometrial Cancer Treatment

• With a fast track designation, the FDA will facilitate tulmimetostat’s clinical development.

• A fast track designation also allows for an expedited review of applications submitted to the FDA regarding tulmimetostat.

• The tulmimetostat development program is the third program by MorphoSys AG to receive an FDA fast track designation.

The FDA has granted fast track designation to the second-generation EZH1/EZH2 inhibitor, tulmimetostat (CPI-0209), for the treatment of patients with advanced, recurrent, or metastatic endometrial cancer who harbor ARID1A mutations and whose disease progressed on frontline treatment.1

According to MorphoSys AG, developer of tulmimetostat, by inhibiting the EZH1 and EZH2 genes, tulmimetostat can revive tumor suppressor gene and other silenced genes. Treatment with tulmimetostat is being investigation in a phase 1/2 clinical trial of patients with advanced solid tumors and lymphomas (NCT04104776).

“Receiving fast track designation from the FDA for tulmimetostat in ARID1A-mutated endometrial cancer underscores this investigational therapy’s potential in a patient population with limited treatment options,” said Tim Demuth, MD, PhD, chief research, and development officer at MorphoSys, in a press release. “The preliminary results from our phase 1/2 study of tulmimetostat are very promising. We will continue to generate data from this study across tumor types to inform our future development plans for tulmimetostat, both as a monotherapy and in combination with other treatments.”

Reproductive cancer | Image Credit: Crystal light - www.stock.adobe.com

Preliminary results were presented at the 2023 American Society of Clinical Oncology Annual Meeting. The study included 47 patients who received up to 28 cycles of tulmimetostat 350 mg, once daily. Following a Simon 2-stage design, cohorts were eligible for expansion to stage 1 if a complete or partial response (PR) was achieved.2

Of the 5 patients evaluated for efficacy in the endometrial cancer cohort of the study, the best response was a partial response, which was observed in 2 patients. One patient had stable disease and 2 patients were not evaluable. Similarly, in the urothelial cancer, ovarian clear cell carcinoma, lymphoma, and mesothelioma cohorts, best responses were PRs. Based on the objective response rates (ORR) demonstrated, the endometrial cancer cohort was eligible for stage 2 expansion along with ovarian cancer and mesothelioma cohorts.

The most any-grade frequent treatment-emergent adverse events (TEAEs) were thrombocytopenia (51.6%), diarrhea (45.2%), nausea (37.1%), anemia (30.6%), fatigue (29.0%), alopecia (25.8%), dysgeusia (24.2%), vomiting (21.0%), and neutropenia (17.7%). The most frequent grade ≥ 3 TEAEs were thrombocytopenia (27.4%), anemia (16.5%), neutropenia (14.5%), and diarrhea (12.9%).

The study of tulmimetostat in patients with advanced solid tumors and lymphomas is ongoing. The primary end point being explored in phase 2 is ORR, and the secondary end points include adverse events, changes in laboratory values, area under the curve (AUC) vs time AUC, and the maximum observed plasma concentration. All end points are being assessed over an 18-month timeframe.3

Patients eligible for inclusion in the study are those with a life expectancy of at least 12 months, an ECOG performance status of 0 or 1, as well as adequate bone marrow, renal, and liver function. For inclusion in the endometrial cancer cohort specifically, patients are required to have histologically or cytologically confirmed disease and know ARID1A mutation. Patients must also be previously treated with at least 1 prior line of therapy, have a documented microsatellite instability or deficient mismatch repair tumor, and measurable disease per RECIST v1.1.

_REFERENCES:

_{1. MorphoSys receives U.S. FDA fast track designation for tulmimetostat in endometrial cancer. News release. MorphoSys AG. September 12, 2023. Accessed September 14, 2023. https://tinyurl.com/2p9rfvfb}

_{2. Drescher C, Walter HS, Gastinne T, et al. EZH2/EZH1 inhibitor tulmimetostat (CPI-0209) in patients with advanced solid tumors or hematologic malignancies: Preliminary phase II results. J Clin Oncol. 2023;41(suppl 16): 3094. doi:10.1200/JCO.2023.41.16_suppl.3094}

_{3. A study of CPI-0209 in patients with advanced solid tumors and lymphomas. ClinicalTrials.gov. Updated October 6, 2022. Accessed September 14, 2023. https://tinyurl.com/mpm75xj3}