Changing the Paradigm of Breast Cancer Treatment: MBQ-167 as a First-in-Class Metastatic Breast Cancer Therapeutic
Abstract
The critical challenges of breast cancer treatment are: (i) management of advanced primary disease with or without regional and/or distant metastases and (ii) the prevention of metastasis, which typically manifests itself in a more aggressive manner where none of the currently available standard treatments can cure the disease. Moreover, while the 5-year survival of early-stage disease has reached nearly 99%, this achievement, unfortunately, comes at the price of frequent overdiagnosis and overtreatment, leading to significant morbidity and a markedly reduced quality of life, if not premature death. Lastly, although given to most breast cancer patients, current adjuvant therapies have been shown to deliver only a marginal impact on survival. The recurrent disease often demonstrates acquired resistance to previously effective breast cancer chemotherapy agents. Notably, at this time, there is no treatment to eradicate or prevent the formation of metastasis, the latter being linked strongly to the recurrence of breast cancer. MBQ Pharma has set out to address these unmet medical needs in breast cancer treatment by targeting related signaling molecules that play key roles in regulating tumor growth, metastasis formation, and conferring resistance to standard tumor therapies. Rac1 and Cdc42, when overactive, appear to be causal in these pathogenetic processes, not currently addressed by existing therapies. As a first success, the MBQ Pharma lead compound, MBQ-167, is an unparalleled high-affinity dual-action inhibitor of both Rac1 and Cdc42 and has been shown to markedly reduce tumor growth and eradicate and prevent metastasis formation in breast cancer animal models. In addition, MBQ-167 markedly inhibited the growth of a panel of solid tumor cell lines. MBQ-167 also reduced stem cell-like mammosphere growth of triple-negative breast cancer cells, a micrometastases model that can lay dormant for many years with dangerous potential for recurrence. Therefore, this study will address the overarching challenges to revolutionize treatment regimens by replacing them with more effective, less toxic alternatives, improve quality of life, and reduce mortality. Subsequently, MBQ Pharma developed a pharmaceutical MBQ-167 orally administered formulation. Notably, the preclinical program revealed an excellent safety profile, good bioavailability, and pharmacokinetics. Based on the encouraging preclinical data, which points towards a paradigm-changing potential of MBQ-167 and its excellent safety profile, the U.S. Food and Drug Administration (FDA) approved Investigational New Drug (IND) for a phase 1 open-label, first-in-human trial of oral MBQ-167 as single agent in subjects with advanced breast cancer. The primary objective of the phase 1 study is to determine the maximally tolerated dose of MBQ-167 as a single agent administered orally, twice daily, continuously for 21 days in subjects with advanced breast cancer. Approximately 72 participants will be screened to achieve enrollment in the phase 1 for an estimated total of 24-48 evaluable participants. As secondary parameters, pharmacokinetics and pharmacodynamics profiles will be assessed. Following completion of the phase 1 trial, the further development program will aim to assess the efficacy of MBQ-167 in treating breast cancer metastasis both in early and advanced stages of the disease. Ultimately, the role of MBQ-167 in preventing disease recurrence will be assessed. Following successful completion of the phase 1 trial, where we will determine the maximum tolerated dose, we plan to conduct phase 2 trials for MBQ-167 and expect to achieve a patient-related outcome in the next 5 years. If successful, MBQ-167 and other potential pipeline candidates have excellent prospects to effectively treat advanced metastatic breast cancer, solve the issue of recurrent disease arising from dormant cancer cells, and overcome tumor-acquired resistance to current standard treatment. Based on
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310381
Entities
People
- Jose Rodriguez
Organizations
- United States Army