A phase I, multicenter, open-label study of UB-VV111 in combination with rapamycin in relapsed/refractory CD19+ B-cell malignancies.
Background: Autologous, ex vivo-manufactured chimeric antigen receptor (CAR) T cells directed against CD19 have demonstrated clinical activity. These products have gained approvals in the relapsed/ refractory (R/R) setting in multiple B-cell malignancies (BCMs), including large B-cell lymphoma (LBCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). However, challenges in product availability due to limited manufacturing capacity, the need for apheresis and lymphodepletion, failure to prior ex vivo CAR T therapy, and the level of patient fitness needed to wait for and receive ex vivo autologous CAR T therapy all pose significant challenges to the field, presenting significant unmet clinical need. UB-VV111 is a third-generation, self-inactivating, replication-incompetent lentiviral vector (LVV) investigational drug product comprising an envelope with cocal virus fusion glycoprotein (cocal) and surface engineered with a membrane-bound multidomain fusion (MDF) protein. The MDF protein contains CD58, CD80, and anti-CD3 single-chain variable fragment (scFv) components that provide both T-cell tropism and activation signals thought to be critical for effective CAR T-cell generation. UB-VV111 addresses the limitations of currently available autologous CD19-directed CAR T therapies to deliver a product that would generate CD19-directed cells in the patient. UB-VV111 is to be administered by either intranodal (IN) or intravenous (IV) route of administration (ROA). Administration of UB-VV111 by either the IN or IV ROA is expected to transduce T cells to generate CAR T cells designed to bind to CD19 antigen to mediate cell killing and express the rapamycin-activated cytokine receptor (RACR) system which, in the presence of rapamycin, is designed to enhance specific enrichment and expansion of transduced cells. Methods: Study UB-VV111-01 (INVICTA, [NCT06528031CO]) is a first-in-human, global, multicenter, dose-finding study of UB-VV111 administered IN or IV +/- rapamycin in CAR-naïve and CAR-exposed subjects with R/R LBCL and CLL/SLL. Dose escalation will proceed independently for each ROA using a Bayesian optimal interval (BOIN) design. Confirmation of CD19 expression will be required for all subjects with prior CD19-directed therapy. Major eligibility criteria include adults with R/R LBCL/CLL/SLL following at least 2 lines of prior therapy who have standard organ function, measurable disease according to Lugano 2014 (LBCL) or iwCLL 2018 (CLL/SLL), ECOG 0 or 1, and no prior allogeneic transplant. Primary objectives include determining the safety profile, maximum tolerated/administered dose, and recommended Phase 2 dose of UB-VV111 +/- rapamycin. Secondary/exploratory objectives include measuring preliminary antitumor activity (magnitude and durability), as well as translational correlates of safety/efficacy.
Disclaimer
This material on this page is ©2025 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Similar Abstracts
Abstract
2023 ASCO Annual Meeting
Effect of bispecific B7H3 x CD19 CAR T cells on host CD19 expression and CAR T cell engraftment.
First Author: Navin R. Pinto
Abstract
2023 ASCO Annual Meeting
Efficacy of function-enhanced, re-activatable, dual-specific CAR T cells pre-loaded with oncolytic virus for immunotherapy of high-grade glioma.
First Author: Mason Webb
Abstract
2023 ASCO Annual Meeting
Phase 1 results with anti-CD19 allogeneic CAR T ALLO-501/501A in relapsed/refractory large B-cell lymphoma (r/r LBCL).
First Author: Frederick L. Locke
Abstract
2021 ASCO Annual Meeting
First-in-human data of ALLO-501A, an allogeneic chimeric antigen receptor (CAR) T-cell therapy and ALLO-647 in relapsed/refractory large B-cell lymphoma (R/R LBCL): ALPHA2 study.
First Author: Frederick Lundry Locke
