Phase 1 Trial of CA-4948 Recruiting Non-Hodgkin’s Lymphoma Patients

A Phase 1 clinical trial is recruiting relapsed or refractory non-Hodgkin’s lymphoma patients to determine the safest and most effective dose of the oral therapy CA-4948. The trial is now treating patients in its fifth dosing group, Curis announced.

CA-4948, developed by Curis in collaboration with Aurigene, is a small molecule that works by inhibiting the enzyme interleukin-1 receptor-associated kinase 4 (IRAK4). In normal circumstances, this protein plays an essential role in innate immune responses, but common mutations in lymphoma — in the MYD88 gene — are known to overactivate IRAK4, contributing to cancer progression.

While MYD88 itself is not fit for therapeutic targeting, the signaling of MYD88 is mediated almost entirely via IRAK4, making IRAK4 a promising target in diseases driven by aberrant MYD88 signaling.

The ongoing trial (NCT03328078) is expected to include 110 participants across 10 clinical sites in the U.S. Its primary goal is to determine the treatment’s safety and identify the recommended dose for further testing.

The study is divided into two parts. First, patients will receive ascending doses of CA-4948 to define its maximum tolerated dose. Each dosing group will include up to six participants. Those in the fifth group are now receiving the treatment in a twice-daily 200 mg dose.

After determining the appropriate dose and dosing regimen, the study will include non-Hodgkin’s lymphoma and acute myeloid leukemia patients in its dose expansion part. Participants must have exhausted all standard therapeutic options, and lymphoma patients may or may not have MYD88 mutations — which cause IRAK4 overactivation.

“This is an important milestone in the execution of our clinical program,” James Dentzer, Curi’s president and chief executive officer, said in a press release.

“Last fall, we reorganized the company to heighten focus on clinical execution and laid out an aggressive goal to advance to the fifth cohort (200 mg) in time for a midyear 2019 release of initial data. We are pleased to announce that we have begun dosing the fifth cohort sooner than expected and we reiterate our plan to report initial clinical data this summer,” Dentzer added.

In addition to the CA-4948 trial, Curis is conducting a Phase 1 trial (NCT02812875) of CA-170 in patients with advanced solid tumors and lymphomas. Patients recruitment is still open.

CA-170 is a dual inhibitor of VISTA and PD-L1, two important inhibitors of T-cell responses.