With a partial clinical hold in place, patient enrollment must halt in the phase 1 NX-2127-001 trial.
A partial clinical hold has been placed by the FDA on the phase 1 NX-2127-001 study (NCT04830137) of NX-2127 for the treatment of various B-cell malignancies.1
The placement of this hold follows the Nurix’s communication with the FDA regarding its intention to transition to an improved manufacturing process. With the hold in place, screening and enrollment of new patients has been paused. Those currently enrolled in the trial who continue to derive clinical benefit may remain on the study and receive treatment in accordance with the ongoing study protocol.
The FDA and Nurix are working to resolve the partial clinical hold as soon as possible. Other drug programs being developed by the company are not affected by the NX-2127 manufacturing process improvement.
“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. "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 and cereblon neo-substrates IKZF1 and IKZF3. The efficacy and safety of the agent is currently assessed in a phase 1 trial for the treatment of patients with relapsed/refractory B-cell malignancies.2
In phase 1a, the dose-escalation portion of the study, the safety and tolerability of NX-2127 will be evaluated in adult patients with relapsed/refractory B-cell malignancies. Those enrolled in this portion of the study must have required and received at least 2 previous systemic therapies and have no other treatments known to provide clinical benefit.
In phase 1b, the efficacy of NX-2127 at the doses selected in phase 1a will be evaluated in up to 5 cohorts of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no BTK C481 mutation, BTK C481 mutation-positive CLL/SLL, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, primary central nervous system lymphoma, diffuse large B-cell lymphoma, or Waldenstrom macroglobulinemia.
Primary end points include dose-limiting toxicities, establishing the maximum tolerated dose and/or recommended phase 1b doses of NX-2127, clinical activity of NX-2127 at the recommended phase 1b doses based on overall response rate, and adverse events. Secondary end points include pharmacokinetics, duration of response, progression-free survival, overall survival, safety and tolerability, complete response (CR) rate, and CR with incomplete marrow recovery as assessed by the investigator.