Phase 1 Evaluation of the Safety and Pharmacokinetics of First-in-Class N-Myristoylation Inhibitor PCLX-001 in Patients with Relapsed/Refractory Acute Myeloid
Abstract
Topic Area: The Fiscal Year 2021 (FY21) Peer Reviewed Cancer Research Program (PRCRP) Topic Area to be addressed by this proposed research is Blood cancers. Military Focus Area: The FY21 PRCRP Military Health Focus Area to be addressed is: Mission Readiness - Gaps in cancer prevention, early detection/diagnosis, prognosis, and/or treatment that may impact mission readiness and the health and well-being of military members, Veterans, their beneficiaries, and the general public. Objective: Acute Myeloid Leukemia (AML) is an aggressive cancer of the blood. In the U.S. alone, approximately 19,940 new cases of AML were diagnosed in 2020, with an estimated 11,180 deaths occurring in the same time period. The current primary treatment option for patients with AML is chemotherapy. Unfortunately, relapse rates remain high, and the 5-year survival for AML patients on standard of care agents is 12.6%. Although there have been several recently approved therapies for AML patients, outcomes are far from satisfactory and death rates remain high. Therefore, we are assessing a new drug – known as PCLX-001 (aka DDD86481) – as a therapeutic option for patients with AML. The objective of this research is to determine the dosage at which PCLX-001 can be used in a manner which is both safe and effective in patients. In addition, we are looking to assess certain enzymes as markers of (1) response to treatment and (2) disease outcome. Contribution and Benefit: This research aims to help patients who suffer from AML by providing an effective and safe therapy option with better long-term health outcomes and a lower relapse rate. Ultimately, this promising approach has the potential to significantly improve survival rates for patients living with AML. Near Term Impact: As a devastating disease, AML clinical treatment is in need of a novel therapeutic approach to lower the rate of relapse and thus improve morbidity and mortality. In the above proposed research, we are looking at a novel therapeutic approach to help those suffering from AML. Preliminary data from cell and animal studies has shown PCLX-001 to be a safe and effective treatment. The current study will help us determine the optimal dose to administer to patients and preliminary understanding of response rates. Success of this clinical trial will enable us to move onto phase 2 clinical trials, further testing the effectiveness of PCLX-001. Therefore, the clinical trial in this proposed research will potentially enable this treatment option to make it to market in the next few years. Overarching Challenge: The FY21 PRCRP Overarching Challenge to be studied is: Transform cancer treatment through the identification of novel biomarkers and new targets especially for advanced disease (metastatic and/or recurrence); improve immunotherapy; and eliminate the risks of therapy-associated toxicity. As mentioned above, the impact of developing a more effective long-term treatment for AML will result in more patients achieving a complete remission and the rest living longer. Military Relevance: The FY21 PRCRP Military Health Focus Area to be studied is Mission Readiness - Gaps in cancer prevention, early detection/diagnosis, prognosis, and/or treatment that may impact mission readiness and the health and well-being of military members, Veterans, their beneficiaries, and the general public. Indeed, Army personnel exposed to low levels of ionizing radiation, especially the Veteran population involved in the SMOKY atmospheric nuclear weapons in 1957, has shown significant increased mortality by leukemia and other complications. PCLX-001 has demonstrated the potential to inhibit AML cancer cell growth and kill AML cancer cells, which if confirmed in this clinical program, will aid military personnel and Veterans suffering from the after-effects of exposures to radiation and chemicals.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211080
Entities
People
- Naveen Pemmaraju
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army