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

Start date

Apr 13, 2022

Status verified

Apr 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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