A Phase 1/2 Study of UB-VV400 With Rapamycin in Relapsed/Refractory B-cell Malignancies

• UB-VV400 (Genetic): UB-VV400 is a gene therapy that generates CD22-directed CAR T cells in the body.
• Rapamycin (sirolimus) (Drug), also known as Rapamune: Rapamycin is a drug approved by the FDA for indications unrelated to cancer.

Primary outcomes

• Phase 1: Percentage of participants with common adverse events (AEs) [Up to 2 years after UB-VV400 administration]: Percentage of participants with commonly reported AEs overall and by severity
• Phase 2: Overall response rate (ORR) [Up to 2 years after UB-VV4001 administration]: Percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR)

Secondary outcomes

• Phase 1: Overall response rate (ORR) [Up to 2 years after UB-VV400 administration]: Percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR)
• Phase 1 and Phase 2: Complete response rate (CRR) [Up to 2 years after UB-VV400 administration]: Percentage of participants with a best overall response (BOR) of complete response (CR)
• Phase 1 and Phase 2: Pharmacokinetics (PK) of UB-VV400 [Up to 8 days after UB-VV400 administration]: Maximum concentration (Cmax), time to maximum concentration (Tmax), and AUC (area under the concentration vs time curve) for UB-VV400
• Phase 2: Percentage of participants with common AEs [Up to 2 years after UB-VV111 administration]: Percentage of participants with commonly reported AEs overall and by severity
• Phase 2: Duration of response (DOR) [Up to 2 years after UB-VV400 administration]: Duration from first evidence of response (CR or PR) to date of first evidence of disease progression or death, whichever is earlier
• Phase 2: Progression-free survival (PFS) [Up to 2 years after UB-VV400 administration]: Duration from first administration of UB-VV400 to the first evidence of disease progression or death from any cause, whichever is earlier.
• Phase 2: Overall survival (OS) [Up to 2 years after UB-VV400 administration]: Duration from first administration of UB-VV400 to death from any cause
• Phase 2: Quality of life (QOL) [Up to 2 years after UB-VV400 administration]: Performance on 2 QoL scales: EuroQol instrument EQ-5D-5L and Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. 18 years or older
2. Provides voluntary written informed consent
3. Relapsed or refractory large B-cell lymphoma (LBCL)
4. Measurable disease according to Lugano 2014 criteria
5. Confirmed CD22 expression
6. No serious concomitant diseases or active/uncontrolled infections
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Adequate organ function

Exclusion Criteria:

1. Women who are pregnant or breastfeeding
2. Current isolated central nervous system (CNS) involvement
3. Prior allogeneic bone marrow transplant, gene therapy, or adoptive cell transfer (except tumor-infiltrating lymphocytes, CAR-NK cells, T-cell receptor \[TCR\] fusion constructs, TCR T cells, and CAR T cells)
4. History of or active human immunodeficiency virus (HIV)
5. Active or chronic hepatitis B, or active hepatitis C
6. Systemic immunodeficiency diseases, except for well-controlled Type I diabetes or thyroid disease
7. Ongoing CNS disease that would preclude neurologic assessment
8. Uncontrolled angina or other acute heart disease
9. Currently receiving treatment in another interventional clinical trial.

• Luke Walker, MD, Study director, Umoja Biopharma