FDA Lifts Partial Clinical Hold on NX-2127 Trial in B-Cell Malignancies

The FDA originally placed a partial clinical hold on NX-2127 as part of the phase 1a/1b clinical trial in November 2023.

The FDA has lifted its partial clinical hold on the phase 1a/1b NX-2127-001 trial (NCT04830137) assessing treatment with NX-2127 for adult patients with relapsed/refractory B-cell malignancies, according to a press release from Nurix Therapeutics, the developers of the agent.¹

Developers plan to continue enrollment of patients as part of a standard dose-escalation study in the phase 1a/1b trial. Patients with aggressive non-Hodgkin lymphoma, including those with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) who have previously demonstrated sustained complete responses, will be prioritized for this study. Additionally, those who are currently enrolled on the NX-2127-001 trial and are experiencing clinical benefit with the experimental agent may continue study treatment based on protocol.

“We are pleased with the timely resolution of the partial clinical hold, which allows us to reinitiate enrollment in the NX-2127 phase 1 study utilizing drug product from our new manufacturing process,” Paula G. O’Connor, MD, executive vice president and head of clinical development at Nurix, said in the press release.¹

The FDA originally placed a partial clinical hold on NX-2127 as part of the phase 1a/1b clinical trial in November 2023.² The regulatory agency placed the hold on trial enrollment due to developers’ intentions of adopting a new manufacturing process for NX-2127.

“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,” Arthur T. Sands, MD, PhD, president, chief executive officer, and board director at Nurix, said in a press release at the time of the clinical hold.² “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 the FDA to introduce the improved NX-2127 manufacturing process and drug product into our clinical development plan.”

Investigators previously presented findings from the phase 1a/1b NX-2127-001 trial at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition. Among the patients with chronic lymphocytic leukemia (CLL) who were evaluable for efficacy, treatment with NX-2127 yielded 9 partial responses (PRs) or PRs with rebound lymphocytosis, and there were 11 patients who had stable disease.³ Among patients with non-Hodgkin lymphoma, investigators reported 2 complete responses (CRs) and 1 PR.

Study treatment resulted in 2 dose-limiting toxicities, which included cognitive disturbance in 1 patient with CLL who received 300 mg of NX-2127 and another with marginal zone lymphoma who had neutropenia following a 300 mg dose. Common any-grade treatment-emergent adverse effects (TEAEs) included fatigue (48.9%), neutropenia (42.6%), and hypertension (36.2%). Additionally, grade 3 or higher TEAEs included neutropenia (38.3%), hypertension (14.9%), and anemia (12.8%).

“NX-2127 had a manageable safety profile that was consistent with previous reports of Bruton tyrosine kinase [BTK]-targeted and immunomodulatory therapies and treatment with NX-2127 resulted in encouraging and durable responses in a heavily pretreated patient population including patients with BTK resistance mutations in both non-Hodgkin lymphoma and in CLL,” lead study author Alexey Danilov, MD, PhD, associate director of the Toni Stephenson Lymphoma Center and Professor in the Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, said in a presentation of the data.

Investigators of the first-in-human, multi-center, open-label, dose-escalation, and cohort-expansion phase 1a/1b NX-2127-001 trial are assessing the preliminary efficacy and safety of NX-2127 in patients with relapsed/refractory B-cell malignancies. The trial includes those with CLL, DLBCL, follicular lymphoma, MCL, and marginal zone lymphoma.

References

1. Nurix Therapeutics announces U.S. FDA lifts partial clinical hold on NX-2127 phase 1 trial Nurix cleared to introduce new chirally controlled NX-2127 drug product and resume enrollment of new patients into the study. News release. Nurix Therapeutics, Inc. March 11, 2024. Accessed March 11, 2024. https://tinyurl.com/9sjkrr2b
2. Nurix Therapeutics announces partial clinical hold for NX-2127 phase 1 trial. News release. Nurix Therapeutics, Inc. November 1, 2023. Accessed March 11, 2024. https://bit.ly/3FNeJbV
3. Danilov A, Tees MT, Patel K, et. al. A first-in-human phase 1 trial of NX-2127, a first-in-class Bruton's tyrosine kinase (BTK) dual-targeted protein degrader with immunomodulatory activity, in patients with relapsed/refractory B cell malignancies. Blood. 2023;142 (suppl 1):4463. doi:10.1182/blood-2023-179872