FDA Grants Fast Track Designation to Novel BTK Inhibitor for Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

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The FDA has granted Fast Track Designation to Nurix Therapeutics, Inc’s investigational Bruton’s tyrosine kinase (BTK) inhibitor NX-5948 for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) following at least two lines of therapy that includes a BTK inhibitor and a BCL2 inhibitor.¹ NX-5948 has previously demonstrated that it is highly potent across a range of tumor cell lines with BTK inhibitor–resistance, which is an important treatment consideration for heavily pretreated patients with CLL and SLL, according to Nurix.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 CEO of Nurix, said in a press release.¹ “This designation follows encouraging safety and efficacy data from our ongoing Phase I clinical trial, demonstrating early promise of clinical benefit with potential for durable outcomes. The receipt of Fast Track Designation is especially timely given our plans to accelerate enrollment in the Phase I trial of NX-5948 with the goal of enabling a pivotal study for NX-5948 as rapidly as possible.”

The novel, oral, small molecule degrader was developed to attach to BTK and the cereblon E3 ligase complex, which leads to degradation of both wild-type and mutated forms of BTK, according to Nurix Therapeutics.² The FDA designation follows positive data from the dose escalation stage of the Phase Ia/Ib NX-5948-301 trial (NCT05131022).

Preliminary data presented during the 2023 American Society of Hematology Annual Meeting and Exposition analyzed daily oral dosing of NX-5948 in patients with relapsed or refractory B-cell malignancies. The study showed a clinical benefit in six of seven patients with CLL administered doses ranging from 50 mg to 200 mg, with three ongoing partial responses as of the data cutoff date of October 17, 2023.

In terms of safety and adverse events (AEs), NX-5948 was well-tolerated across all evaluated dosing ranges with no dose-limiting toxicities (DLTs) or treatment-related serious AEs and no treatment-emergent AEs (TEAEs) that led to discontinuation. Notably, there were no reported cases of atrial fibrillation or hypertension associated with the drug.

Investigators are actively enrolling patients in the United States, United Kingdom, and the Netherlands. Data for higher dose levels and longer treatment duration are expected in 2024, according to Nurix Therapeutics.

The first-in-human, dose-escalation cohort-expansion of NX-5948-301 is evaluating the safety and clinical activity of NX-5948 in adults with CLL; SLL; Waldenström macroglobulinemia; mantle cell lymphoma; marginal zone lymphoma; follicular lymphoma; diffuse large B-cell lymphoma; and primary central nervous system lymphoma.²

Researchers are enrolling patients 18 years of age and older with histologically confirmed, measurable or evaluable B-cell malignancies.^2,3 The trial’s primary endpoints are incidence of DLTs and TEAEs, and to establish the recommended Phase Ib dose and/or the maximum tolerated dose. The primary endpoints for the Phase Ib portion are safety and anti-tumor activity.³

References

1. 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. January 16, 2024. Accessed January 18, 2024. https://finance.yahoo.com/news/nurix-therapeutics-receives-u-fda-210100427.html
2. 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
3. A study of NX-5948 in adults with relapsed/​refractory B-cell malignancies. ClinicalTrials.gov. Updated January 10, 2024. Accessed January 18, 2024. https://clinicaltrials.gov/study/NCT05131022