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


Following changes to the manufacturing process, the phase 1 study of NX-2127 in B-cell malignancies has been cleared to continue by the FDA.

3D illustration of blood cells: ©pinkeyes - stock.adobe.com

3D illustration of blood cells: ©pinkeyes - stock.adobe.com

  • In November 2023, the FDA placed the phase 1 trial (NCT04830137) of NX-2127, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, on a partial clinical hold.
  • The hold followed the company’s intention to improve the manufacturing process.
  • With this FDA clearance, the study evaluating the agent in relapsed or refractory B-cell malignancies may resume.

The FDA has lifted the partial clinical hold on the phase 1 trial of NX-2127, a novel BTK inhibitor, for the treatment of patients with relapsed or refractory B-cell malignancies.1

The hold was put in place in November 2023 following communication by Nurix Therapeutics, NX-2127’s creator, to the FDA of its intention to improve manufacturing processes.

“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,” said Paula G. O’Connor, MD, executive vice president and head of clinical development at Nurix, in a press release.

Enrollment in the phase 1 trial will be reinitiated, and patients with aggressive forms of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), who have previously achieved durable responses, will be prioritized. Patients who are currently enrolled in the trial will continue to receive treatment according to the study protocol.

In December 2023, findings from the study of NX-2127 were presented at the American Society of Hematology Annual Meeting. The findings showed that NX-2127 demonstrated dose-dependent pharmacokinetics and a mean half-life of 2 to 4 days among all patient cohorts. Further, rapid BTK degradation was observed.2

“NX-2127 had a manageable safety profile that was consistent with previous reports of BTK-targeted and immunomodulatory therapies and treatment with NX-2127 resulted in encouraging and durable responses in a heavily pretreated patient populations including patients with BTK resistance mutations in both non-Hodgkin lymphoma and in [chronic lymphocytic leukemia (CLL)],” 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.

About the Phase 1 Study of NX-2127

The phase 1a/1b study of NX-2127 has an estimated enrollment of 160 patients with relapsed or refractory B-cell malignancies, including CLL, small lymphocytic lymphoma, MCL, follicular lymphoma, marginal zone lymphoma, primary central nervous system lymphoma (PCNSL), DLBCL, or Waldenstrom macroglobulinemia.3

The study’s primary end points are dose-limiting toxicities, maximum tolerated dose, overall response rate, and incidence of adverse events and laboratory abnormalities. Secondary end points include pharmacokinetics, duration of response, progression-free survival, overall survival, and complete response rate.

To be eligible for study participation, patients must be 18 years of age or older, have an ECOG performance status of 0 or 1 for non-PCNSL indications, an ECOG performance status of 0 to 2 for PCNSL indications, and adequate marrow and organ function. Patients with history of autoimmune disease, toxicities from previous anticancer treatments, or active infection are not eligible to participate.

The study has an anticipated completion date of December 2025.

1. Nurix Therapeutics announces U.S. FDA lifts partial clinical hold on NX-2127 phase 1 trial. News release. Nurix Therapeutics, Inc. March 11, 2024. Accessed March 11, 2024. https://tinyurl.com/47se8sv5
2. 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
3. A study of NX-2127 in adults with relapsed/refractory B-cell malignancies. ClinicalTrials.gov. Updated November 7, 2023. Accessed March 11, 2024. https://clinicaltrials.gov/study/NCT04830137
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