Study of NX-5948 Versus Pirtobrutinib in R/R CLL/SLL

A Phase 3, Randomized, Open-label, Multicenter Study of NX-5948 Versus Pirtobrutinib in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

The study will evaluate the efficacy and safety of NX-5948 (bexobrutideg) versus pirtobrutinib in participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who are relapsed or refractory to prior covalent Bruton tyrosine kinase inhibitor (cBTKi) treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: B-cell Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: NX-5948; Drug: Pirtobrutinib

• Study Type: Interventional
• Enrollment (Estimated): 620
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Additional Site Contact Information; Phone Number: 415-417-3418; Email: clinicaltrials@nurixtx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Adequate organ and bone marrow function
• Confirmed diagnosis of CLL/SLL that meets iwCLL 2018 criteria for diagnosis and systemic treatment
• Received at least one prior line of therapy for CLL/SLL that included a cBTKi and must have documented disease progression during treatment with, or after discontinuation of, the cBTKi
• Participants with SLL must have measurable disease by computed tomography (CT) per iwCLL

Key Exclusion Criteria:

• Known or suspected prolymphocytic leukemia or Richter's transformation at any time preceding enrollment
• Investigational agent or anticancer therapy within 5 half-lives or 14 days (whichever is shorter) prior to planned start of study treatment
• Ongoing systemic corticosteroids ≥10 mg/day prednisone or equivalent
• Previously treated with a BTK degrader or a noncovalent BTKi
• Myocardial infarction, unstable angina, unstable symptomatic ischemic heart disease, placement of a coronary arterial stent, or any other significant cardiac condition within 6 months of planned start of study treatment
• Thromboembolic events, stroke, or intracranial hemorrhage within 6 months of planned start of study treatment

Note: Other Inclusion/Exclusion criteria may apply as defined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: NX-5948	Drug: NX-5948; Administered orally once daily; Other Names: Bexobrutideg
Experimental: Arm B: Pirtobrutinib	Drug: Pirtobrutinib; Administered orally once daily per prescribing information; Other Names: JAYPIRCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) as assessed by Independent Review Committee (IRC)	Time from randomization to disease progression or death due to any cause, whichever is earlier	Up to approximately 3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomization to death from any cause	Up to approximately 6 years
PFS as assessed by the investigator	Time from randomization to disease progression or death due to any cause, whichever is earlier	Up to approximately 6 years
Objective response rate (ORR) with and without partial response with lymphocytosis (PR-L) as assessed by IRC and investigator	Percentage of participants with best overall response of complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR) or nodular PR, or PR-L (for ORR with PR-L), as assessed per 2018 International Workshop on CLL (iwCLL) guidelines	Up to approximately 6 years
Duration of response with and without PR-L as assessed by IRC and investigator	Time from the date of the first response to documented disease progression or death due to any cause, whichever is earlier	Up to approximately 6 years
Time to next anti-CLL/SLL treatment as assessed by IRC and by investigator	Time from randomization to the date of next anti-CLL/SLL treatment	Up to approximately 6 years
Change from baseline in global health status/quality of life on the European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire C30 with CLL module (EORTC QLQ-C30-CLL17)	Percentage of participants with a clinically meaningful change from baseline using the EORTC QLQ-C30-CLL17 questionnaire to assess global health and overall quality of life	Baseline and up to approximately 6 years
Change from baseline in EuroQol-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)	Percentage of participants with a clinically meaningful change from baseline using the EQ-5D-5L questionnaire to assess health outcomes	Baseline and up to approximately 6 years
Number of participants with treatment-emergent adverse events		Up to approximately 6 years
Pharmacokinetic profile of NX-5948	NX-5948 concentrations in blood samples	Up to Cycle 13 Day 1 (each cycle is 28 days)
Number of participants with clinically significant changes from baseline in laboratory parameters	Laboratory parameters may include hematology, clinical chemistry, and urinalysis	Up to approximately 6 years
Number of participants with clinically significant changes from baseline in vital signs	Vital signs include blood pressure, heart and respiratory rates, pulse oximetry, and temperature	Up to approximately 6 years

Collaborators and Investigators

• Sponsor: Nurix Therapeutics, Inc.
• Investigators: Study Director: Study Director, Nurix Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): June 1, 2032

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Lymphocytic Leukemia (CLL); BTKi; Small Lymphocytic Lymphoma (SLL); Pirtobrutinib; B-cell malignancy; Degrader; Bexobrutideg
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; pirtobrutinib
• Other Study ID Numbers: NX-5948-306; 2025-524145-27-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No