FDA Grants Fast Track Designation to UB-VV111 for R/R B-Cell Malignancies

The FDA has awarded fast track designation to UB-VV111 for the treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL) and chronic lymphocytic leukemia (CLL) who have received at least 2 prior lines of therapy.1

An ongoing phase 1 trial (NCT06528301) is investigating the safety and efficacy of UB-VV111 in patients with CD19-positive B-cell malignancies.

“This fast track designation marks a key milestone in the advancement of in vivo CAR T-cell therapies,” Luke Walker, MD, chief medical officer of Umoja Biopharma, the developer of UB-VV111, stated in a news release. “UB-VV111 continues to lead the in vivo CAR T-cell field in the United States, and today’s announcement further reinforces its potential to address unmet needs in the treatment of those living with relapsed/refractory B-cell malignancies. This achievement is a testament to the dedication of our clinical trial sites and to the patients who inspire our mission every day.”

Notably, in 2024, the FDA cleared the investigational new drug (IND) application for UB-VV111 for the treatment of patients with hematologic malignancies.2 This was the first FDA clearance of an IND application for an in vivo CAR T-cell therapy.1 The phase 1 trial was initiated following this clearance.

What Is the Mechanism of Action of UB-VV111?

UB-VV111 is an investigational, third-generation, self-inactivating, replication-incompetent lentiviral vector off-the-shelf treatment that generates CD19-targeted CAR T cells in vivo.3 This product is surface engineered with a membrane-bound multidomain fusion protein containing CD58, CD80, and CD3-directed single-chain variable fragment components that provide T-cell tropism, as well as activation signals that may assist in effective CAR T-cell generation. UB-VV111 also has an envelope containing cocal virus fusion glycoprotein. This product was designed to address the limitations of currently approved autologous CD19-directed CAR T-cell therapies by generating anti-CD19 cells directly in the patient.

What Was the Design of the Phase 1 Trial of UB-VV111 in Relapsed/Refractory B-Cell Malignancies?

This first-in-human, global, multicenter, dose-escalation and -confirmation study is enrolling patients at least 18 years of age with relapsed or refractory LBCL or CLL who have measurable disease per Lugano 2014 criteria (LBCL) or International Workshop on CLL 2018 criteria (CLL).4 Patients need to have no serious concomitant diseases or active or uncontrolled infections, an ECOG performance status of 0 or 1, and adequate organ function. Patients who have been previously treated with CD19-directed therapy need to have biopsy-confirmed CD19 expression following completion of that therapy.

Patients will be excluded if they are pregnant or breastfeeding; have current isolated central nervous system (CNS) involvement; have ongoing CNS disease precluding neurologic assessment; have previously undergone allogeneic bone marrow transplant, gene therapy, or adoptive cell transfer (except for CAR T-cell therapy); have a history of or active human immunodeficiency virus; have active hepatitis B or C; have systemic immunodeficiency or autoimmune diseases, except for well-controlled type I diabetes or thyroid disease; have uncontrolled angina or other acute heart disease; or are currently being treated in another interventional clinical trial.

Patients will receive a single dose of UB-VV111 either alone or followed by rapamycin (Rapamune) treatment.3,4 UB-VV111 will be administered either intranodally or intravenously. Each route of administration will follow independent dose-escalation and -expansion designs.

The primary end points are the safety profile, as well as the maximum tolerated dose, maximum administered dose, and recommended phase 2 dose of UB-VV111 with or without rapamycin. The secondary end point is overall response rate. Exploratory end points include further preliminary efficacy findings; the pharmacokinetics and immunogenicity of UB-VV111 particles and CAR T cells; and translational correlative findings regarding biomarkers, safety, and efficacy.

References

1. Umoja Biopharma announces that UB-VV111 receives FDA fast track designation for relapsed/refractory B-cell malignancies. News release. Umoja Biopharma. September 30, 2025. Accessed September 30, 2025. https://www.umoja-biopharma.com/news/umoja-biopharma-announces-that-ub-vv111-receives-fda-fast-track-designation-for-relapsed-refractory-b-cell-malignancies/
2. Umoja Biopharma announces FDA Clearance of IND application for UB-VV111, a CD19 directed in situ CAR T for hematologic malignancies. News release. Umoja Biopharma. July 31, 2024. Accessed September 30, 2025. https://www.umoja-biopharma.com/news/umoja-biopharma-announces-fda-clearance-of-ind-application-for-ub-vv111-a-cd19-directed-in-situ-car-t-for-hematologic-malignancies/
3. Gacia JR. A phase I, multicenter, open-label study of UB-VV111 in combination with rapamycin in relapsed/refractory CD19+ B-cell malignancies. J Clin Oncol. 2025;43(suppl 16):TPS2681. doi:10.1200/JCO.2025.43.16_suppl.TPS2681
4. A phase 1 study of UB-VV111 with and without rapamycin in relapsed/​refractory CD19+ B-cell malignancies. ClinicalTrials.gov. Updated July 15, 2025. Accessed September 30, 2025. https://clinicaltrials.gov/study/NCT06528301