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

Conditions

• Chronic Lymphocytic Leukemia (CLL)
• Diffuse Large B Cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL)
• Mantle Cell Lymphoma (MCL)
• Marginal Zone Lymphoma (MZL)
• Primary Central Nervous System Lymphoma (PCNSL)
• Secondary Central Nervous System Lymphoma (SCNSL)
• Small Lymphocytic Lymphoma (SLL)
• Waldenstrom Macroglobulinemia (WM)

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• NX-5948 — DRUG
  Oral NX-5948

Study Details

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.

Key Dates

First listed

Nov 23, 2021

Start date

Apr 13, 2022

Status verified

Jun 2026

Primary completion

Jan 31, 2027

Completion

Jan 31, 2028

Study Design

Enrollment

572 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1a Dose Escalation
  Multiple dose levels of NX-5948 to be evaluated; determination of Maximum Tolerated Dose/Phase 1b recommended dose(s)
• Experimental: Phase 1b Part 1 Cohort 1 in CLL or SLL with prior BTKi and BCL2i
  CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor, unless previously deemed ineligible for a BCL-2i. Patients enrolled in CLL/SLL arm will be randomized to one of two dose levels.
• Experimental: Phase 1b Part 1 Cohort 2 in CLL/SLL with non-C481S BTK mutations
  Prior exposure to both BTKi and BCL-2i (unless deemed ineligible for BCL-2i by Investigator at the time of study enrollment) and documented BTK mutation other than C481S within 6 months prior to study entry
• Experimental: Phase 1b Part 1 Cohort 3 in CLL/SLL with prior non-covalent BTKi
  CLL/SLL with prior exposure to ncBTKi and are BCL-2i naïve.
• Experimental: Phase 1b Part 1 Cohort 4 in CLL/SLL with TP53 or 17p deletion, 2L, prior BTKi
  Patients with documented TP53 mutation or 17p deletion and 1 prior line of therapy that included a BTKi and are BCL-2i naïve.
• Experimental: Phase 1b Part 1 Cohort 5 in CLL/SLL with 2L+, prior BTKi
  Patients with at least 1 prior line of therapy that included a BTKi and are BCL-2i naïve.
• Experimental: Phase 1b Part 1 Cohort 6 in MCL
  Non-blastoid MCL with prior exposure to a BTKi and an anti-CD20 monoclonal antibody (mAb)-based chemoimmunotherapy regimen
• Experimental: Phase 1b Part 1 Cohort 7 in MZL
  MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and an additional line of therapy
• Experimental: Phase 1b Part 1 Cohort 8 in WM (3L+)
  WM with prior exposure to a BTKi and at least an additional line of therapy
• Experimental: Phase 1b Part 1 Cohort 9 in WM (2L)
  WM following upfront therapy with a BTKi
• Experimental: Phase 1b Part 1 Cohort 10 in DLBCL
  DLBCL which transformed from indolent lymphoma or Richters transformation with prior exposure to an anthracycline (unless previously deemed ineligible to receive), an anti-CD20 mAb-based chemoimmunotherapy regimen, and an additional line of therapy
• Experimental: Phase 1b Part 1 Cohort 11 in FL
  FL (grade 1-3a) with prior exposure to an anti-CD20 mAb-based chemoimmunotherapy regimen and an additional line of therapy
• Experimental: Phase 1b Part 1 Cohort 12 in PCNSL/SCNSL
  PCNSL following at least 1 prior line of therapy that included a BTKi (2L+) or following 2 or more prior lines of therapy (3L+), or SCNSL patients meeting criteria for a non-CLL/SLL cohort enrolling that disease with secondary CNS involvement of lymphoma
• Experimental: Phase 1b Part 1 Cohort 13 in PCNSL
  PCNSL following upfront therapy and with no prior exposure to a BTKi (2L).
• Experimental: Phase 1b Part 2 in CLL or SLL with prior BTKi and BCL-2i
  CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor
• Experimental: Phase 1b Part 1 Cohort 14 in first-line WM
  Treatment-naïve WM deemed unfit for chemoimmunotherapy
• Experimental: Phase 1b Part 1 Cohort 15 in BTKi-naive CLL/SLL
  First-line (1L) or second-line+ (2L)+ CLL/SLL with no prior exposure to a BTKi
• Experimental: Phase 1b Part 1 Cohort 16 in CLL/SLL with secondary warm autoimmune hemolytic anemia (wAIHA)
  BTKi-exposed R/R CLL or SLL with secondary wAIHA
• Experimental: Phase 1b Part 1 Cohort 17 in CLL/SLL with CNS involvement
  BTKi-exposed R/R CLL or SLL with CNS involvement

Primary Outcome Measure

Number of participants with protocol specified dose-limiting toxicities [ Time Frame: Up to 24 months ]

Central Contacts

• Additional Site Contact Information
  +1 (415) 417-3418
  [email protected]

Locations (18)

Find similar trials in Duarte, CA

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