MEI Pharma Announces Update of Ongoing Phase 1 Study Evaluating Oral CDK9 Inhibitor Voruciclib Alone and in Combination with Venetoclax in Patients with Acute Myeloid Leukemia or B-Cell Malignancies
‒ Voruciclib alone or in combination with venetoclax was generally well tolerated with no significant myelosuppression ‒
– Encouraging preliminary efficacy signal demonstrated with voruciclib alone and at the first dose level with voruciclib in combination with venetoclax –
“These initial results provide encouraging support for the potential of voruciclib administered in combination with venetoclax to address a common resistance mechanism to venetoclax therapy and deliver improved clinical benefit to patients without significant myelosuppression,” said Dan Gold, Ph.D., president and chief executive officer of MEI Pharma. “We look forward to disclosing more data from this study around year-end, including data from patients receiving higher doses of voruciclib plus venetoclax, to further evaluate the potential of the combination to safely provide synergistic benefit to patients.”
Phase 1 Study Overview and Preliminary Safety and Efficacy Results
The Phase 1 study is a two stage, open-label, 3+3 dose escalation and expansion study evaluating voruciclib as a monotherapy and in combination with venetoclax, a BCL-2 inhibitor. The primary objectives of the study are to determine the safety and biologic effective dose of voruciclib monotherapy or voruciclib in combination with venetoclax. Secondary objectives of the study include assessing the preliminary efficacy, pharmacokinetics, pharmacodynamics, and biomarkers of voruciclib monotherapy or voruciclib in combination with venetoclax.
The first stage of the study evaluated the dose and schedule of voruciclib as a single-agent in patients with relapsed and refractory (“R/R”) acute myeloid leukemia (“AML”) or B-cell malignances after failure or standard therapies. Stage 2 of the study is evaluating voruciclib in combination with standard dose venetoclax in patients with R/R AML.
Part 1, the voruciclib monotherapy dose escalation/expansion stage of the study, enrolled 40 patients with R/R AML and B-cell malignancies, the first 16 dosed daily continuously at 50 and 100 mg and the following 24 dosed on an intermittent schedule (14 consecutive days on therapy in a 28-day cycle) at 100, 150 and 200 mg. All patients were heavily pretreated with a median of 3 prior therapies (range 1-7). The most common (≥
Part 2 of the study is currently evaluating the combination of voruciclib and venetoclax in patients with R/R AML. The first cohort in the dose escalation phase enrolled 6 patients administered 50 mg of voruciclib every other day for 14 days followed by 14 days of no therapy in a 28-day cycle, plus standard dose venetoclax. All patients were heavily pretreated with a median of three prior therapies. Notably, all patients previously progressed after receiving treatment with venetoclax. No DLTs or overlapping bone marrow toxicities were observed. The disease control rate was
“We are gratified to see preliminary evidence of clinical activity with voruciclib in combination with venetoclax at the lowest dose level evaluated,” stated Richard Ghalie, M.D., chief medical officer of MEI Pharma. “These results are supportive of the hypothesis that voruciclib may reverse a mechanism of resistance to venetoclax.”
About Voruciclib
Voruciclib is an orally administered cyclin-dependent kinase 9 (“CDK9”) inhibitor with potential to treat both hematological malignancies and solid tumors. It is in clinical development for acute myeloid leukemia and B-cell malignancies. Applications in solid tumors are also being considered.
The CDK family of proteins are important cell cycle regulators responsible for the control of cell proliferation, differentiation, apoptosis, and DNA repair. CDK9, one of several members of the CDK family of proteins, functions as a gene transcription controller and is also involved in regulating protein degradation. Specifically, CDK9 is a promising target to treat a range of cancers because of its role in controlling two other proteins often dysregulated in cancerous cells: myeloid leukemia cell differentiation protein ("Mcl-1") and the MYC proto-oncogene protein ("MYC")
MCL1 is a member of the family of anti-apoptotic proteins which, when elevated, may prevent the cell from undergoing cell death. Inhibition of CDK9 blocks the production of Mcl-1, which is an established resistance mechanism to the B-cell lymphoma 2 ("BCL2") inhibitor venetoclax (marketed as Venclexta®).
MYC regulates cell proliferation and growth. Upregulation of MYC is implicated in many human cancers and is frequently associated with poor prognosis and unfavorable patient survival. CDK9, in addition to being a transcription factor for MYC, also decreases phosphorylation of MYC protein that is implicated in stabilizing MYC in KRAS mutant cancers. Targeting MYC directly has historically been difficult, but CDK9 is a promising approach to target this oncogene.
About Acute Myeloid Leukemia and B-cell Malignancies
Acute myeloid leukemia (“AML”) is a fast-growing hematologic cancer in which too many myeloblasts (a kind of immature white blood cell) are found in the bone marrow and blood. AML usually gets worse quickly if it is not treated. It can spread outside the blood to other parts of the body, including the lymph nodes, spleen, liver, central nervous system (brain and spinal cord), skin, gums, and testicles. AML is most common in older adults.*
B-cell malignancies are a type of hematologic cancer that forms in B cells (a kind of immune system cell). B-cell lymphomas may be either indolent (slow-growing) or aggressive (fast-growing). Most B-cell lymphomas are non-Hodgkin lymphomas. There are many different types of B-cell non-Hodgkin lymphomas, such as chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma.**
About MEI Pharma
MEI Pharma, Inc. (Nasdaq: MEIP) is a pharmaceutical company focused on developing potential new therapies for cancer. MEI Pharma’s portfolio of drug candidates includes clinical stage candidates with differentiated mechanisms of action intended to address unmet medical needs and deliver improved benefit to patients, either as standalone treatments or in combination with other therapeutic options. For more information, please visit www.meipharma.com. Follow us on Twitter @MEI_Pharma and on LinkedIn.
Forward-Looking Statements
Under
* National Cancer Institute (2023, May 17). Retrieved from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/aml
** National Cancer Institute (2023, May 17). Retrieved from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/b-cell-lymphoma
View source version on businesswire.com: https://www.businesswire.com/news/home/20230523005347/en/
David A. Walsey
Tel: 858-369-7104
investor@meipharma.com
Source: MEI Pharma, Inc.