Study of NX-5948 in Combination With Other Agents in Adults With B-cell Malignancies

An Open-label, Multicenter Phase 1b/2 Study to Evaluate the Safety and Efficacy of NX-5948 in Combination With Other Agents in Adults With B-cell Malignancies

The study will evaluate NX-5948 (bexobrutideg) in combination with venetoclax with or without an anti-CD20 antibody (rituximab or obinutuzumab) in second-line or higher (2L+) relapsed/refractory (R/R) or first-line (1L) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Bexobrutideg is an investigational drug designed to target a protein called Bruton tyrosine kinase (BTK), which helps cancer cells grow in certain blood cancers like CLL and SLL. Bexobrutideg is a protein degrader, which means it finds and destroys the BTK in the cell. Venetoclax, rituximab, and obinutuzumab are approved medications that are used to treat CLL/SLL.

The study will look at:

• How safe bexobrutideg is for patients with CLL or SLL when taken with these other treatments
• The effects of bexobrutideg in the body when taken with these other treatments
• How well bexobrutideg treats CLL or SLL when taken with these other treatments

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Adequate organ and bone marrow function
• Measurable disease by computed tomography (CT) per iwCLL
• For R/R CLL/SLL, prior therapy must include treatment with a Bruton tyrosine kinase inhibitor (BTKi)
• For 1L CLL/SLL, confirmed previously untreated CLL/SLL with a clinical indication for systemic treatment that meets iwCLL criteria
• Must sign an informed consent form indicating understanding of the study purpose and procedures and willingness to participate

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
• Radiotherapy within 2 weeks of the first dose of study drug except for focal palliative radiation
• Use of systemic corticosteroids (>20 mg/day prednisone or equivalent) within the 7 days prior to initiation of study treatment excepting those used as prophylaxis for radiodiagnostic contrast
• Previously treated with a BTK degrader
• Previously treated with a BCL-2 inhibitor (BCL-2i) unless eligible for retreatment
• Known central nervous system (CNS) lymphoma or leukemia
• 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.