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A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies

ConditionsChronic Lymphocytic Leukemia (CLL)Small Lymphocytic Lymphoma (SLL)Diffuse Large B Cell Lymphoma (DLBCL)Follicular Lymphoma (FL)Mantle Cell Lymphoma (MCL)Marginal Zone Lymphoma (MZL)Waldenstrom Macroglobulinemia (WM)Primary Central Nervous System Lymphoma (PCNSL)Secondary Central Nervous System Lymphoma (SCNSL)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNurix Therapeutics, Inc.

About this trial

This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years

Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL, SLL, DLBCL (subgroups include Richter-transformed DLBCL, germinal center B-cell type, activated B-cell type, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS), FL, MCL, MZL (subtypes include EMZL, MALT, NMZL, SMZL), WM, or PCNSL.

Patients in Phase 1b (Safety and Cohort Expansion) must have 1 of the following histologically documented B-cell malignancies, must meet criteria for systemic treatment, and must have received prior therapies and/or molecular features based on details described for each cohort: CLL or SLL, DLBCL, MCL, FL, MZL, WM, or PCNSL/SCNSL.

Measurable disease per response criteria specific to the malignancy.

Disqualifiers

Known or suspected active prolymphocytic leukemia or Richter's transformation to Hodgkin's lymphoma prior to study enrollment

Radiotherapy within 2 weeks of planned start of study drug (excluding limited palliative radiation).

Prior systemic chemotherapy within 2 weeks of planned start of study drug.

Prior monoclonal antibody therapy within 4 weeks of planned start of study drug, except for patients enrolling in Cohort 16 (CLL with secondary wAIHA) where a 16-week washout period is required.

Trial design

Design model

Sequential

Treatments tested in this trial

  • NX-5948

    Drug

    Oral NX-5948

Treatment groups

572 Participants
are divided into 19 treatment groups

19

Treatment groups

See each treatment group below.

Group A: Phase 1a Dose EscalationExperimental treatment 1 intervention
Group B: Phase 1b Part 1 Cohort 1 in CLL or SLL with prior BTKi and BCL2iExperimental treatment 1 intervention
Group C: Phase 1b Part 1 Cohort 2 in CLL/SLL with non-C481S BTK mutationsExperimental treatment 1 intervention
Group D: Phase 1b Part 1 Cohort 3 in CLL/SLL with prior non-covalent BTKiExperimental treatment 1 intervention
Group E: Phase 1b Part 1 Cohort 4 in CLL/SLL with TP53 or 17p deletion, 2L, prior BTKiExperimental treatment 1 intervention
Group F: Phase 1b Part 1 Cohort 5 in CLL/SLL with 2L+, prior BTKiExperimental treatment 1 intervention
Group G: Phase 1b Part 1 Cohort 6 in MCLExperimental treatment 1 intervention
Group H: Phase 1b Part 1 Cohort 7 in MZLExperimental treatment 1 intervention
Group I: Phase 1b Part 1 Cohort 8 in WM (3L+)Experimental treatment 1 intervention
Group J: Phase 1b Part 1 Cohort 9 in WM (2L)Experimental treatment 1 intervention
Group K: Phase 1b Part 1 Cohort 10 in DLBCLExperimental treatment 1 intervention
Group L: Phase 1b Part 1 Cohort 11 in FLExperimental treatment 1 intervention
Group M: Phase 1b Part 1 Cohort 12 in PCNSL/SCNSLExperimental treatment 1 intervention
Group N: Phase 1b Part 1 Cohort 13 in PCNSLExperimental treatment 1 intervention
Group O: Phase 1b Part 2 in CLL or SLL with prior BTKi and BCL-2iExperimental treatment 1 intervention
Group P: Phase 1b Part 1 Cohort 14 in first-line WMExperimental treatment 1 intervention
Group Q: Phase 1b Part 1 Cohort 15 in BTKi-naive CLL/SLLExperimental treatment 1 intervention
Group R: Phase 1b Part 1 Cohort 16 in CLL/SLL with secondary warm autoimmune hemolytic anemia (wAIHA)Experimental treatment 1 intervention
Group S: Phase 1b Part 1 Cohort 17 in CLL/SLL with CNS involvementExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Number of participants with protocol specified dose-limiting toxicities

Phase 1a

Time frame
Up to 24 months
2

To establish the maximum tolerated dose and/or recommended Phase 1b dose(s)

Phase 1a

Time frame
Up to 24 months
3

To evaluate the anti-tumor activity of NX-5948 in the dose levels selected for Phase 1b safety expansion based on overall response rate (ORR) as assessed by Investigator

Phase 1b Part 1

Time frame
Up to 3 years
4

Number of participants with treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs, serious adverse events (SAEs), TEAEs leading to study drug discontinuation, deaths due to TEAEs, and all deaths

Phase 1a / Phase 1b Part 1

Time frame
Up to 6 years

Secondary outcomes

1

Pharmacokinetic (PK) profile of NX-5948: Maximum Serum Concentration

Phase 1a / Phase 1b Part 1 and Part 2 - Sampling following the first dose, pre- and post-dose at selected cycles and at the end of treatment

Time frame
Up to 6 years
2

Pharmacodynamic (PD) profile of NX-5948: Changes from baseline of BTK levels in B-cells

Phase 1a / Phase 1b Part 1 and Part 2 - Sampling at screening, following the first dose, pre and post-dose at selected cycles and at the end of treatment

Time frame
Up to 6 years
3

Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator

Phase 1a / Phase 1b Part 1 and Part 2

Time frame
Up to 6 years
4

Duration of response (DOR) as assessed by the Investigator

Phase 1a / Phase 1b Part 1 and Part 2

Time frame
Up to 6 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Nurix Therapeutics, Inc.

Lead sponsor

Source ClinicalTrials.gov
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