UBX-303061 in Subjects With Relapsed/Refractory B-Cell Malignancies

A Phase Ia/Ib, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamic of UBX-303061 in Subjects With Relapsed/Refractory B-Cell Malignancies

This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of UBX-303061 in patients with relapsed/refractory B-cell malignancies.

Key Inclusion Criteria

• Capable of giving signed informed consent
• Age ≥18 years
• ECOG performance status ≤2.
• Phase Ia (dose-escalation part only): Subjects with relapsed and/or refractory B-cell malignancies (CLL/SLL, DLBCL, FL, MCL, WM or MZL) who have received at least 2 prior therapies and for subjects with no available treatment options as per the Investigator's discretion.
• Phase Ib (dose-expansion only): Subjects with relapsed and/or refractory B-cell malignancies who have received at least 2 prior therapies and for subjects with no available treatment options as per the Investigator's discretion, and fit into one of the following groups: CLL/SLL or DLBCL or MCL or FL, WM, MZL
• All subjects must have evaluable or measurable disease based on the appropriate tumor type criteria
• Adequate organ and bone marrow function

Key Exclusion Criteria

• For subjects with lymphoma:

  • Systemic antineoplastic therapy or any experimental therapy within 3 weeks or 5 half-lives, whichever is shorter, before the first dose of study treatment.
  • Therapy with tyrosine kinase inhibitor within 5 half-lives before the first dose of study treatment.
  • Unconjugated monoclonal antibody therapies <6 weeks before the first dose of study treatment.
  • Subjects that have undergone autologous stem cell rescue within 100 days prior to the first dose of study treatment.
  • Subjects that have undergone allogeneic stem cell transplant within 6 months prior to the first dose of study treatment.
  • Subjects with active graft-versus-host disease (GVHD) or on anti-GVHD treatment or prophylaxis.
  • History of chimeric antigen receptor T cell (CAR-T) therapy within 100 days prior to start of study drug.
  • Any immunotherapy within 4 weeks of first dose of study drug.
  • The time from the last dose of the most recent chemotherapy or experimental therapy to the first dose of study drug is <5 times the t1/2 of the previously administered agent(s).

• Previously exposed to BTK degradation therapy

• Malignant disease, other than that being treated in this study.

• Radiotherapy within 2 weeks of the first dose of study treatment

• Known hypersensitivity to BTK degraders or any of the ingredients.

• Impaired cardiac function or clinically significant cardiac disease

• Subjects with history of severe bleeding disorders and known/suspected other autoimmune disease

• Major surgery within 4 weeks of the first dose of study treatment