NX-5948 Receives FDA Fast Track Designation in Relapsed/Refractory CLL/SLL
Findings from a phase 1a/1b trial highlight that treatment with NX-5948 appears to be tolerable among patients with relapsed/refractory B-cell malignancies.
Treatment with NX-5948 was assessed as part of a phase 1a/1b clinical trial (NCT05131022) among patients with relapsed/refractory B-cell malignancies.
The FDA has granted fast track designation to NX-5948 as a treatment for those with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with 2 or more lines of treatment including a Bruton tyrosine kinase (BTK) inhibitor and a BCL2 inhibitor, according to a press release from Nurix Therapeutics, Inc.1
“Fast track designation for NX-5948 is an important recognition of the unmet patient need in CLL, particularly in the growing number of patients whose cancer has progressed following BTK and BCL2 inhibitor therapy,” Arthur T. Sands, MD, PhD, president and chief executive officer at Nurix, said in the press release. “This designation follows encouraging safety and efficacy data from our ongoing phase 1 clinical trial, demonstrating early promise of clinical benefit with potential for durable outcomes.”
Treatment with NX-5948 was assessed as part of a phase 1a/1b clinical trial (NCT05131022) among patients with relapsed/refractory B-cell malignancies. According to findings presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition, the experimental agent yielded no dose-limiting toxicities or treatment-emergent adverse effects (TEAEs) leading to dose reduction or treatment discontinuation.2 Additionally, the most common TEAEs included purpura or contusion (57.1%), nausea (35.7%), and thrombocytopenia (35.7%). Investigators reported that the agent’s pharmacokinetic data supported administering the agent once a day.
Investigators observed early signs of clinical activity among 3 evaluable patients with CLL who received 50 mg of NX-5948. This activity included 1 confirmed partial response and 2 patients with stable disease.
As of June 9, 2023, 14 patients were included in the phase 1a portion and were treated with NX-5948 at 50 mg (n = 7), 100 mg (n = 4), or 200 mg (n = 3) orally once a day. Investigators plan to enroll an approximate total of 110 patients across phase 1a and phase 1b and administer treatment until progressive disease or unacceptable toxicity.
The trial’s primary end points included protocol specified dose-limiting toxicities, anti-tumor activity based on overall response rate, and TEAEs. Secondary end points included pharmacokinetics, complete response rate, duration of response, progression-free survival, and time to next therapy.
Patients 18 years and older with histologically confirmed relapsed/refractory B-cell malignancies including CLL and SLL previously treated with 2 or more lines of therapy were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1, adequate organ and bone marrow function, and measurable disease.
As of the data readout at ASH, the median patient age in the trial was 65 years (range, 46-79). Additionally, most patients were male (71.4%), white (92.9%), and had an ECOG performance status of 1 (78.6%). The most common diagnoses included CLL in 4 patients, diffuse large B-cell lymphoma in 4, mantle cell lymphoma in 3, marginal zone lymphoma in 2, and follicular lymphoma in 1.
Patients received a median of 4.5 (range, 2-10) prior lines of treatment. Among those with CLL, the most common agents administered in prior lines of therapy included BTK inhibitors (n = 4/4) and BCL2 inhibitors (n = 3/4).
References
- Nurix Therapeutics receives U.S. FDA fast track designation for NX-5948 for the treatment of relapsed or refractory CLL and SLL. News release. Nurix Therapeutics, Inc. January 16, 2024. Accessed January 18, 2024. http://tinyurl.com/4da8drrm
- Searle E, Forconi F, Linton K, et al. Initial findings from a first-in-human phase 1a/b trial of NX-5948, a selective Bruton’s tyrosine kinase (BTK) degrader, in patients with relapsed/refractory B cell malignancies. Blood. 2023;142(suppl 1):4473. doi:10.1182/blood-2023-179508
