CA-4948 is the second therapy from the partnership to reach clinical trials. It works by inhibiting the enzyme interleukin-1 receptor-associated kinase 4 (IRAK4), which plays an essential role in innate immune response. Aurigene developed it.
The trial (NCT03328078) will assess the therapy’s safety, pharmacokinetics — or what the body does to the drug — and pharmacodynamics, or how the drug affects the body. Another goal will be to determine the recommended dose of CA-4948 for a Phase 2 trial.
There will be two parts to the trial. The first will be a dose escalation stage that covers patients with relapsed or refractory non-Hodgkin’s lymphoma, or RRNHL. The second will be a dose expansion stage. It will cover RNHL patients with mutations of the MYD88 gene or alterations of the Toll-like receptor (TLR) pathway.
Dose escalation is a progressive increase in the strength of a treatment. Dose expansion involves increasing the number of patients who receive it.
Innate immune pathways use MYD88 protein to send signals through TLRs or interleukin receptors. The signaling activates IRAK4.
Mutations that activate the MYD88 gene are common in one type of diffuse large B-cell lymphoma and in Waldenstrom’s macroglobulinemia. This makes IRAK a target for treating these cancer types.
“We are pleased to announce the advancement of our clinical pipeline with the initiation of the Phase 1 trial for this selective IRAK kinase inhibitor in patients with lymphomas,” Ali Fattaey, the president and CEO at Curis, said in a press release.
CA-4948 displayed promising anti-tumor activity in animal models of lymphomas with MYD88 activating mutations as well as animals with acute myeloid leukemia, myelodysplastic syndromes, and other inflammatory diseases, Fattaey said. Curis and Aurigene plans to test CA-4948 in clinical trials of these diseases in the near future, he added.
“We are delighted with our collaboration that has led to the advancement of the second program into the clinic, an IRAK4-targeting molecule that came out of Aurigene’s discovery efforts over many years,” said CSN Murthy, Aurigene’s CEO.
In addition to the CA-4948 trial, the partners are conducting an ongoing Phase 1 trial (NCT02812875) of CA-170 in patients with advanced solid tumors and lymphomas. It is continuing to recruit participants. You can find more information about it here.
Scientists are also developing IRAK4 inhibitors to treat patients with rheumatoid arthritis.