A Phase 1b/2a Trial of the Anti-IL1RAP Antibody Nadunolimab in Patients with Myelodysplastic Syndrome and Acute Myelogenous Leukemia
Abstract
Topic Area: This proposal addresses the Fiscal Year 2022 Peer Reviewed Cancer Research Program Topic Area of Blood Cancers, and the Military Health Focus Area 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 a type of blood cancer that is usually treated with intensive chemotherapy or a combination of different cancer drugs. Unfortunately, the cancer returns for many patients after treatment, and there is a lack of treatment options for these patients. Myelodysplastic syndrome (MDS) refers to a group of diseases affecting blood stem cells (undefined cells that can become various blood cell types), and in high-risk MDS patients, their disease can transform to AML. A specific type of cancer drug called a hypomethylating agent is used to treat MDS patients, but if patients don t respond to this treatment, they usually have dismal outcomes. A major reason why patients diagnosed with AML or high-risk MDS fail treatment is because of leukemia stem cells, a small population of self-renewing cells, which are insensitive to current treatment regiments and start to re-grow, causing disease relapse. Cantargia s co-founder Thoas Fioretos found a protein (IL1RAP) that has increased expression on these leukemia stem cells, and showed that by targeting this protein, they could kill leukemia stem cells without affecting healthy cells. Cantargia has developed an antibody (nadunolimab) to target this protein, which has shown safety and cancer-killing effects in initial clinical trials, but is yet to be tested in AML and MDS. Contribution and Benefit: This research will help patients with AML and MDS for whom first-line treatments have failed, by providing another treatment option. This adds another therapeutic strategy to the currently lacking armory for AML and MDS. As a highly targeted treatment, it should have limited side effects. Additionally, we will also be studying the effect of the drug at a cellular level, to increase understanding of how it works. Near-Term Impact: This study seeks to determine the optimal dose of nadunolimab to be used in phase 2 trials for the treatment of AML and MDS. Upon successful completion of this project, nadunolimab will advance to the next phase of clinical trials, to further evaluate how effective it is, in its journey to market approval in the next 5-10 years. Overarching Challenge: This proposal targets the Overarching Challenge of Advance immunotherapy across the different PRCRP Topic Areas, because the study drug to be tested is a form of immunotherapy for blood cancers, but has shown therapeutic potential in several solid tumor cancers. Military Relevance: The ultimate goal of this research is to provide another treatment option for high-risk AML and MDS patients that improves their survival rates and quality of life. Improved survival rates may allow an active-duty Service Member to return to full duty, and for their Families, improved relapse rates reduce the amount of time that the Service Member is called home. Both AML and high-risk MDS are diseases most prevalent among the population over the age of 60-65. A substantial proportion of Veterans belong to this age group. Moreover, there have been concerns about higher incidence of MDS/AML among Veterans exposed to environmental toxins, radiation, Agent Orange, etc. The clinical trial proposed in this application addresses the unmet therapeutic need in this population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252311051
Entities
People
- Gautam Borthakur
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army