The first patient has been dosed in a Phase 1 trial testing the investigational cancer therapy PRT1419 in patients with relapsed or refractory blood cancers, including acute myeloid leukemia (AML), Prelude Therapeutics, the therapy’s developer, has announced.
The Phase 1, dose-escalation study (NCT04543305), now undergoing in two clinical sites in Florida, is currently open to adults with AML, as well as multiple myeloma, non-Hodgkin’s lymphoma (NHL), and high-risk myelodysplastic syndromes (MDS), a group of blood cancers that often progress to AML. More information on trial contacts and recruiting sites can be found here. Of note, refractory cancers are those that do not respond to treatment.
PRT1419 is a potent, selective oral inhibitor of the myeloid cell leukemia 1 (MCL1), a protein known to promote the survival of cancer cells, and whose levels are often increased in blood cancers and solid tumors. Therefore, therapies that are able to lower the levels or activity of this protein have the potential to be used to fight cancer.
In preclinical models of AML, multiple myeloma, and lymphoma, treatment with small molecule MCL1 inhibitors have shown signs of efficacy.
Studies in lab-cultured cells and animal models have also confirmed PRT1419’s ability specifically to inhibit MCL1. In animal models of blood cancers, treatment with oral PRT1419 also lowered disease burden when given once weekly.
The Phase 1 study, which follows a dose-escalation design in which patients will be dosed in groups of three, is divided into two phases.
The first is a dose-escalation phase, in which participants will receive increasing doses of the medication for 28 days to determine the optimal dose. This will be carried out in two groups of patients: group A will include those with AML and/or high-risk MDS, and group B will include those with NHL or multiple myeloma.
The second part is an expansion phase, in which patients will be treated with the previously established optimal dose of PRT1419 alone or, for a sub-group of patients with AML or MDS, in combination with standard medications, such as azacitidine (sold as Vidaza and Onureg) or Venclexta (venetoclax).
The study’s main goals include assessing dose-limiting toxicities, and determining the maximum tolerated dose, as well as the recommended dose of the therapy.
Additional goals include assessing the therapy’s safety and tolerability, pharmacokinetic profile, and anti-tumor activity. Pharmacokinetics studies how a medication is taken up, processed, and then eliminated from the body.