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

Eligibility: Inclusion Criteria
  •   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