Partial Clinical Hold Placed on Phase 1 Trial for Investigational Drug for B-Cell Malignancies
The FDA placed a partial hold on a phase 1 trial for the Bruton tyrosine kinase degrader NX-2127 for the treatment of patients with relapsed/refractory B-cell malignancies.
The FDA placed a partial hold on a clinical trial evaluating the investigational Bruton tyrosine kinase (BTK) degrader NX-2127 for the treatment of patients with relapsed/refractory B-cell malignancies, according to a press release from Nurix Therapeutics, Inc.1 The hold was placed after Nurix relayed its intention to improve their manufacturing process for the drug.
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As such, the company has paused screening and enrolling new patients into the phase 1 NX-2127-001 trial (NCT04830137). Patients who are currently enrolled in the trial and who gained clinical benefit will be able to continue receiving the novel treatment in accordance with the trial protocol.
“The initial NX-2127 manufacturing process produced a phase 1 drug product that has yielded important proof-of-concept results with meaningful clinical responses in patients with advanced B-cell malignancies,” said Arthur T. Sands, MD, PhD, president and chief executive officer of Nurix, in a press release.1 "While the partial hold is in effect, we will supply the current drug product for patients who continue on therapy in the phase 1 study and will work expeditiously with FDA to introduce the improved NX-2127 manufacturing process and drug product into our clinical development plan.”
NX-2127 is a novel bifunctional molecule that degrades BTK, in addition to the cereblon neosubstrates Aiolos (IKZF3) and Ikaros (IKZF1). NX-2127-001 is a first-in-human, multicenter, open-label trial analyzing the safety and efficacy of NX-2127 in adults with the advanced B-cell malignancies of chronic lymphocytic leukemia (CLL); small lymphocytic lymphoma (SLL); Waldenström macroglobulinemia (WM); mantle cell lymphoma (MCL); marginal zone lymphoma (MZL); follicular lymphoma (FL); diffuse large B-cell lymphoma (DLBCL); and primary central nervous system lymphoma (PCNSL).2
In the phase 1a dose-escalation portion of the trial, investigators are analyzing the safety and tolerability of NX-2127 at multiple dose levels among patients previously administered two systemic therapies—or a minimum of 1 prior therapy for those with WM or PCNSL—as well as for patients with no other known therapies that have been found to provide a clinical benefit.
The primary endpoints of the phase 1a dose-escalation portion seek to to determine the incidence of protocol-specified dose-limiting toxicities and establish a maximum-tolerated dose and/or a recommended phase 1b dose(s) for the investigational treatment.
The phase 1b dose-expansion portion of the trial will analyze the efficacy of the drug at the dose level identified in the phase 1a portion among a maximum of five patient cohorts previously administered at least two systemic therapies or a minimum of one prior therapy for patients with WM or PCNSL, including patients with CLL or SLL with or without BTK C481 mutations whose disease has progressed on a BTK inhibitor; patients with MCL whose disease progressed on a BTK inhibitor and an anti-CD20 monoclonal antibody–based regimen; patients with FL or MZL whose disease progressed while on an anti-CD20 monoclonal antibody–based regimen; patients with PCNSL whose disease progressed on one or more previous lines of therapy; patients with DLBCL whose disease progressed while on an anti-CD20 monoclonal antibody–based regimen and either an anti-CD19–based regimen, an anthracycline, or another regimen; and patients with WM whose disease progressed during treatment with a BTK inhibitor. The primary end points of the phase 1b portion of the trial are overall response rate and safety.2
Additional ongoing drug programs led by Nurix remain unaffected by the manufacturing process improvements for NX-2127, as the manufacturer works to get the FDA’s partial clinical hold lifted.
References
1. Nurix Therapeutics announces partial clinical hold for NX-2127 phase 1 trial. News release. Nurix Therapeutics, Inc. November 1, 2023. Accessed November 2, 2023. https://ir.nurixtx.com/news-releases/news-release-details/nurix-therapeutics-announces-partial-clinical-hold-nx-2127-phase
2. A study of NX-2127 in adults with relapsed/refractory B-cell malignancies. ClinicalTrials.gov. Updated August 29, 2023. Accessed November 2, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04830137
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