Umoja Biopharma's In Situ CAR-T Therapy Cleared for US Trial in Hematologic Malignancies
The trial will be open to patients with relapsed/refractory large-B-cell lymphoma and chronic lymphocytic leukemia.
The FDA has cleared an investigational new drug (IND) application for Umoja Biopharma's UB-VV111, a gene therapy product intended to create CD19-directed CAR T-cells within the body, allowing the company to go forward with a phase 1 dose escalation trial in hematologic malignancies.1
The trial will be open to patients with relapsed/refractory large-B-cell lymphoma and chronic lymphocytic leukemia, regardless of whether they have previously received treatment with a CAR-T product. Outcome measures for the study will include safety and tolerability, along with clinical antitumor activity of the CAR-T product. The company anticipates that the first patient will be dosed in the trial before the end of the year.
“The IND clearance for UB-VV111 is a significant milestone in Umoja’s mission to develop off-the- shelf therapies that overcome the limitations of current ex vivo cellular immunotherapies,” Andrew Scharenberg, MD, the cofounder and chief executive officer of Umoja, said in a statement.1 “We are proud to be a leader of the in vivo space, aiming to remove many of the barriers and challenges of early- generation ex vivo CAR T-cell therapies, from the difficult, lengthy, and costly manufacturing process to the arduous administration experience. Physicians and patients have been waiting for something better and we are excited to initiate our first clinical trial.”
UB-VV111 is the first of Umoja’s products based on its VivoVecTM gene delivery platform to reach clinical stage development. The platform utilizes third generation lentiviral vectors and a T-cell targeting and activation surface complex. The surface-engineered viral envelope encapsulates a transgene that codes for a CD19-directed CAR and a Rapamycin Activated Cytokine Receptor that is intended to instigate enrichment and expansion of the CAR T-cells.
According to Umoja, in vivo generation of CAR T-cells is expected to circumvent many of the drawbacks and risks of ex vivo CAR-T therapy, such as the wait time for readministration to the patient and the need for lymphodepleting chemotherapy. Notably, UB-VV111 is covered under exclusive option and license agreements between Umoja Biopharma and AbbVie allowing AbbVie to license the product.
Preclinical data regarding UB-VV111 was previously presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.2 The data came from humanized mice and nonhuman primates (NHPs) treated with VivoVec particles.
“The data from these studies show efficient generation of CAR T cells in vivo at the planned clinical trial dose,” Byoung Ryu, PhD, the executive vice president of discovery research & vector biology at Umoja, said in a December 2023 statement.1 “CAR T-cell expansion correlates with rapid and durable B-cell aplasia in NHPs within our study which exceeds the current ex vivo CAR T cell benchmarks. Importantly, we continue to see no acute toxicity associated with VivoVec particle administration.”
Umoja is not the only company currently working on an in vivo approach to CAR-T for the treatment of hematological malignancies.3 Interius BioTherapeutics’ INT2104, an investigational lentiviral vector-based gene therapy that is intended to treat B-cell malignancies through the creation of CD20-directed CAR T-cells and CAR natural killer cells in vivo, received Human Research Ethics Committee approval and clinical trial notification (CTN) clearance from Australia’s Therapeutic Goods Administration (TGA) in July 2024. In light of the CTN clearance, Interius expects to initiate plans for a phase 1 clinical trial (INVISE, Injectable Vectors for In Situ Engineering) for INT2104 within the final quarter of 2024.
