Dr Alencar on the Ongoing Development of NX-5948 in CLL and B-Cell Malignancies

"We still have [to perform] more studies focusing on tolerability, but the drug is so active, we know it’s going to move forward. Now, the challenge [is defining] where [this regimen] fits in CLL."

Alvaro Alencar, MD, a hematologist/oncologist, associate professor of clinical medicine, and associate chief medical officer at the University of Miami Sylvester Comprehensive Cancer Center, discussed research supporting the continued investigation of the novel BTK degrader NX-5948 in chronic lymphocytic leukemia (CLL) and other B-cell malignancies.

Findings from an ongoing phase 1 trial (NCT05131022) evaluating NX-5948 in patients with these hematologic malignancies were presented at the 2024 ASH Annual Meeting. The overall response rate (ORR) among efficacy-evaluable patients who underwent at least 1 response assessment at 8 weeks (n = 49) was 75.5% (95% CI, 61.1%-86.7%). Among patients with extended follow-up (n = 38), the ORR increased to 84.2% (95% CI, 68.7%-94.0%), indicating that responses deepened over time. Responses were reported to be both rapid and durable, with some patients remaining on NX-5948 therapy for over 12 months, and others exceeding 18 months of therapy.

Although these findings underscore the antitumor activity of NX-5948, further investigation is required to optimize its use, Alencar stated. Dose refinement remains ongoing, and additional studies are needed to better characterize the tolerability profile of the agent, he added. Despite these early-phase challenges, the clinical activity observed with this agent supports its continued development, Alencar emphasized.

The evolving therapeutic arsenal in CLL raises key questions regarding the optimal integration of NX-5948 into the treatment paradigm, he continued. These include whether the agent should be used in earlier lines of therapy, whether it could serve as a backbone in combination regimens, and how best to sequence it alongside or after other BTK-targeted therapies, he detailed.

The clinical activity and potential novel mechanism of NX-5948 support the broader need for additional drug classes in CLL, Alencar said. Continued investigation will be required to determine the most appropriate role for NX-5948 in clinical practice, but these early data suggest that this agent could represent a valuable addition to the armamentarium for CLL management, he concluded.