A Study of NX-5948 in Adults With CLL/SLL Previously Treated With a Bruton's Tyrosine Kinase Inhibitor and a B-cell Lymphoma-2 Inhibitor (DAYBreak CLL-201)

A Single-arm, Phase 2, Open-label, Multicenter Study to Evaluate NX-5948 in Adults With Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Previously Exposed to a Bruton's Tyrosine Kinase Inhibitor (BTKi) and a B-cell Lymphoma-2 Inhibitor (BCL-2i)

This is a study for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with a BTK inhibitor (covalent and non-covalent) and a BCL-2 inhibitor. The main purpose of this study is to test if NX-5948 (bexobrutideg) works to treat patients with CLL/SLL. Participation could last up to 5 years, and possibly longer, if the disease does not progress.

The main purpose of this study is to test if NX-5948 works to treat patients with R/R CLL/SLL. NX-5948 is a BTK degrader and works by destroying the BTK protein to stop all its actions. This is different from a BTK inhibitor which works by blocking only the kinase action of BTK. This study aims to answer these questions:

• How well does NX-5948 work to treat patients who have previously received a BTK inhibitor and a BCL-2 inhibitor?
• How safe is NX-5948 and can patients take NX-5948 as long as they need to?
• What is the amount of NX-5948 in the bloodstream over time when given to patients with CLL/SLL?

All patients in the study will receive NX-5948 orally until their cancer gets worse or if there are other reasons to stop taking NX-5948. Patients will have their cancer and other health check-ups regularly while they are taking NX-5948. If a patient's cancer has not gotten worse and they stop taking NX-5948, they will continue to have cancer check-ups until their cancer gets worse.

Inclusion Criteria:

• Age: ≥ 18 years
• Confirmed relapsed/refractory CLL/SLL that meets iwCLL criteria for diagnosis and systemic treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Must have received a covalent BTK inhibitor (BTKi), a non-covalent BTKi, and a BCL-2 inhibitor either in separate lines of therapy or in combination; a line of therapy is considered 2 or more consecutive cycles of a systemic anti-CLL/SLL regimen
• Participants with SLL must have measurable disease by radiographic assessment
• Adequate organ and bone marrow function
• Must sign an informed consent form indicating that he or she understands the purpose of the procedures required for the study and is willing to participate

Exclusion Criteria:

• Known or suspected prolymphocytic leukemia or Richter's transformation before entering study

• Investigational agent or anticancer therapy within 5 half-lives or 14 days (whichever is shorter) before planned start of study drug

  • Antibody therapy must stop at least 4 weeks before the first dose of study drug
  • No other systemic anticancer therapy is allowed at the same time as this study; exception: continuation of hormonal therapy for breast and prostate cancer is allowed, if they are not on the list of prohibited concomitant medications in this study

• Palliative limited-field radiotherapy within 7 days of the first dose of study or broad field radiotherapy within 28 days of first dose of study drug

• Use of systemic corticosteroids >20 mg/day prednisone or equivalent within the 7 days before start of study drug except for those used as premedication for radio diagnostic contrast

• Use of systemic immunosuppressive drugs other than systemic corticosteroids within 60 days before the first dose of study drug

• Previously treated with a BTK degrader

• Previous chimeric antigen receptor (CAR) T-cell therapy or allogeneic or autologous hematopoietic cell transplant within the past 90 days prior to enrollment

• Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within 6 months of planned start of study drug

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