UB-VV400 in Combination With Rapamycin in Relapsed or Refractory B-cell Malignancies

Exclusion Criteria

• •1. Women who are pregnant or breastfeeding.
• •2. Subjects with current isolated central nervous system (CNS) tumor involvement.
• •3. Subjects with a prior malignancy whose clinical course or management has the potential to interfere with the safety and/or efficacy evaluation of the clinical trial.
• •4. Prior treatment with any of the following: allogeneic bone marrow transplantation, gene therapy, or adoptive cell transfer of any kind except for CAR T-cell therapy.
• •5. Treatment with prior CD22-directed therapy except for UB-VV400.
• •6. History of or active human immunodeficiency virus (HIV).
• •7. Active hepatitis B (HepB) or hepatitis C (HepC).
• •8. For subjects receiving rapamycin: a. History of angioedema; b. Pneumonitis (Grade 3 or greater).
• •9. Ongoing Grade \> 2 toxicities from the last line of anticancer therapy.
• •10. Use of the following:
• •1. Therapeutic systemic doses of corticosteroids (defined as \> 20 mg prednisone equivalent) within 72 hours before dosing with UB-VV400.
• •2. Approved targeted therapies:
• •i. Small molecules: within 3 half-lives before dosing with UB-VV400 (see package insert). ii. Antibodies: within 14 days before dosing with UB-VV400. iii. CAR T therapy: within 28 days before dosing with UB-VV400. c. Autologous stem cell transplant within 28 days before dosing with UB-VV400. d. Cytotoxic chemotherapy (eg, alkylators, anthracyclines) within 14 days before dosing with UB-VV400.
• •e. Any experimental agent (ie, not approved for disease/indication or with accepted consensus guidelines recommendation) within 4 weeks before dosing with UB-VV400 unless progression has been documented and a minimum of 3 half-lives has elapsed.
• •f. Any immune-suppressing agent within 28 days before dosing with UB-VV400 (eg, tacrolimus, mycophenolate mofetil, immunosuppressive antibodies such as anti-tumor necrosis factor \[TNF\]/IL-6).
• •g. Radiation within 4 weeks before dosing with UB-VV400 (palliative radiation to a symptomatic lesion\[s\] is allowed if at least one additional, non-irradiated, measurable lesion remains present to assess response).
• •h. Prophylactic treatment with short-acting oral antiretroviral medications within 7 days before UB-VV400 administration. Long-acting antiretroviral prophylaxis is not allowed within 2 years of UB-VV400 treatment.
• •11. Allergies to rapamycin or supportive medications required for CAR T-cell toxicity management (eg, tocilizumab).
• •12. Systemic autoimmune diseases or immunodeficiency diseases (except for well-controlled type I diabetes with hemoglobin A1C \[HbA1c\] less than 8% or well-controlled thyroid disease, as assessed by the treating physician).
• •13. Ongoing CNS diseases (eg, seizure disorder, tremor, history of cerebral vascular accident \[CVA\]/recurrent transient ischemic attack \[TIA\]) that would preclude evaluation of immune effector cell-associated neurotoxicity syndrome (ICANS).
• •14. Presence of uncontrolled angina or other acute uncontrolled heart disease. Myocardial infarction within the previous 6 months. New York Heart Association (NYHA) Class III or IV. History of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• •15. Actively receiving treatment in other interventional clinical trials. Note: continued follow-up on previous trials is allowed for survivorship, but no further investigational agents or assessments will be allowed.