EMA Grants PRIME Designation to NX-5948 for R/R CLL/SLL

The highly selective BTK degrader NX-5948 has received PRIME designation from the European Medicines Agency (EMA) for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who received prior treatment with a BTK inhibitor and a BCL2 inhibitor, according to a news release from Nurix Therapeutics.¹

Medicines that could fulfill an unmet medical need and show potential benefit for patients based on early clinical data are eligible for PRIME designation by the EMA. This initiative provides enhanced support to developers of medicines with positive data in order to optimize and accelerate development.

In the news release, Nurix Therapeutics announced that pivotal trials investigating NX-5948 will initiate in 2025.

“PRIME 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 inhibitor and BCL2 inhibitor therapy,” Arthur T. Sands, MD, PhD, president and chief executive officer of Nurix Therapeutics, stated in the news release. “This designation follows encouraging safety and efficacy data from our ongoing phase 1 clinical trial, demonstrating early promise of clinical benefit as well as mechanistic data supporting the activity of NX-5948 independent of mutations that confer resistance to covalent and noncovalent BTK inhibitors.”

The investigational, orally bioavailable, brain penetrant, small molecule BTK degrader is designed to specifically eliminate BTK, which is a key growth signaling protein in B cells. Preclinical data have shown that NX-5948 is highly potent against a range of tumor cell lines resistant to BTK inhibitors.

A first-in-human, multicenter, open-label phase 1 trial (NCT05131022) is currently evaluating NX-5948 in patients with relapsed/refractory B cell malignancies.²

In the phase 1a dose-escalation portion of the trial, investigators will evaluate the safety and tolerability of NX-5948 in patients at least 18 years of age with relapsed/refractory B-cell malignancies who have received at least 2 prior lines of therapy and for whom no other therapies are known to provide clinical benefit. Patients with the following B-cell malignancies are eligible for enrollment: CLL/SLL, non-germinal center B-cell subtype (non-GCB), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Waldenström macroglobulinemia, marginal zone lymphoma (MZL), follicular lymphoma (FL) including those with secondary central nervous system involvement, and primary central nervous system (CNS) lymphoma (PCNSL).

The phase 1b portion of the investigation will evaluate the efficacy of NX-5948 at the selected dose(s) identified in phase 1a in up to 4 cohorts of patients with histologically confirmed relapsed/refractory B-cell malignancies who have received at least 2 prior lines of therapy (or at least 1 prior line for patients with Waldenstrom macroglobulinemia or PCNSL).

These 4 cohorts will include:

• CLL/SLL, including those with secondary CNS involvement
• Non-GCB DLBCL or MCL, including those with secondary CNS involvement
• MZL, Waldenström macroglobulinemia, or FL including those with secondary CNS involvement
• PCNSL

Notably, 2 dose levels will be evaluated in the CLL/SLL cohort in phase 1b.

Key exclusion criteria for both portions of the study include known or suspected prolymphocytic leukemia or Richter's transformation to Hodgkin lymphoma; active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia; and a history of grade 2 or higher hemorrhage within 28 days of starting study treatment.

The study’s primary end points are dose-limiting toxicities, establishing the maximum tolerated dose, antitumor activity, and safety. Secondary end points included pharmacokinetics and additional efficacy end points, including complete response rate, duration of response, progression-free survival, and time to next therapy.

References

1. Nurix Therapeutics receives PRIME designation from the European Medicines Agency for NX-5948 for the treatment of relapsed or refractory chronic lymphocytic leukemia. News release. Nurix Therapeutics. November 20, 2024. Accessed November 21, 2024. https://ir.nurixtx.com/news-releases/news-release-details/nurix-therapeutics-receives-prime-designation-european-medicines
2. A study of NX-5948 in adults with relapsed/​refractory B-cell malignancies. ClinicalTrials.gov. Updated July 11, 2024. Accessed November 21, 2024. https://clinicaltrials.gov/study/NCT05131022