FDA Grants Fast Track Designation to UB-VV111 in Select B-Cell Malignancies

The FDA has granted fast track designation to UB-VV111, an investigational, off-the-shelf CD-19-directed CAR T cell in vivo product, as a treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL) and relapsed/refractory chronic lymphocytic leukemia (CLL) following 2 or more lines of therapy, according to a press release from the developer, Umoja Biopharma.¹

Previously, in July 2024, the developer announced that the FDA had cleared UB-VV111’s investigational new drug application.² At the time of the release, the first patient was expected to be dosed by the end of 2024.

The dose-escalation and dose-confirmation phase 1 INVICTA-1 trial (NCT06528301) is currently evaluating the safety and antitumor activity of UB-VV111 with and without rapamycin in patients with LBCL and CLL. Details about the trial were shared in a poster at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.³

It was found in nonclinical in vitro and in vivo pharmacology studies that UB-VV111 selectively binded, activated, and transduced T cells through the MDF protein to generate CAR T cells expressing an anti–CD19 CAR and the rapamycin-activated cytokine receptor system; that UB-VV111–generated CAR T cells mediated antigen-specific toxicity, cytokine secretion, and proliferation; and that CAR T-cell generation and activity were observed with and without rapamycin, but treatment with rapamycin selectively enriched and expanded CAR T cells.

Further, a 13-week Good Laboratory Practice toxicity study demonstrated that UB-VV111 was well-tolerated in CD34-humanized mice, with no UB-VV111–related mortalities or effects on body weight, clinical observations, human cytokine expression, hematology, chemistry, or gross pathology. The agent also achieved a favorable pharmacodynamic profile.

“This fast track designation marks a key milestone in the advancement of in vivo CAR T cell therapies,” stated Luke Walker, MD, chief medical officer of Umoja Biopharma, in the press release.¹ “UB-VV111 continues to lead the in vivo CAR T cell field in the US, 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.”

The study was designed to assess the intranodal and intravenous routes of administration in patients with relapsed/refractory CLL or LBCL who are either CAR T cell-exposed or CAR T cell-naïve. In the dose-finding portion of the trial, the Bayesian optimal interval design was used to identify the maximum tolerated/administered doses of UB-VV111 with and without rapamycin. In the dose-expansion portion of the trial, patients were randomly assigned to dose levels demonstrating safety and activity to further optimize phase 2 dosing, with dosing potentially performed on a single route of administration or within a single patient group.

Enrolled patients were 18 years or older with relapsed or refractory LBCL or CLL after 2 prior lines of therapy who had measurable disease per Lugano 2014 criteria or International Workshop on CLL 2018 criteria, an ECOG performance status of 0 or 1, and adequate organ function. Additionally, those who previously received CD19-directed therapy must have had biopsy confirming CD19 expression following completion of prior CD19-directed therapy.

Exclusion criteria included current isolated central nervous system (CNS) involvement, history of or active HIV, ongoing CNS disease that precludes neurologic assessment, and current receipt of treatment in another interventional clinical trial. Patients also could not have received prior allogeneic bone marrow transplantation, gene therapy, or adoptive cell transfer, and could not have systemic autoimmune or immunodeficiency diseases.

The primary end points of the trial were determining the safety profile of UB-VV111 with and without rapamycin, and determining the maximum tolerated dose, maximum administered dose, and recommended phase 2 dose of UB-VV111. The secondary end point was preliminary efficacy, including overall response rate; exploratory end points were the pharmacokinetics and immunogenicity of UB-VV111 particles and CAR T cells, the translational correlation of biomarkers and observed safety and efficacy, and further preliminary efficacy data.

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 October 1, 2025. https://tinyurl.com/76zybhzn
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 October 1, 2025. https://tinyurl.com/4w26r8xw
3. Garcia J, Dehner C, Teoh J, Brandes A, Wallis W. 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;53(suppl 16):TPS2681. doi:10.1200/JCO.2025.43.16_suppl.TPS2681