This is an exploratory, open-label, investigator-initiated trial (IIT) of the safety, efficacy, and PK/Pd of UB-VV400 alone and in combination with rapamycin in adult subjects with R/R LBCL. LBCL will include subjects with aggressive lymphoma, defined as diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), including high-grade lymphoma (HGL) with double/triple hit DLBCL; transformed DLBCL (tDLBCL), including Richter's transformation; follicular lymphoma Grade 3B (FL3B); and primary mediastinal B-cell lymphoma (PMBCL). The study will include subjects who have had prior CD19-directed CAR T-cell exposure and subjects who are CAR T cell-naive. Clinical unmet need exists in both populations.
The objective of this study is to determine the MTD/MAD and following study of UB-VV400 administered alone and in combination with rapamycin. The dose-finding (DF) portion will evaluate the safety profile of UB-VV400 administered at various dose levels (DLs) alone (Stage 1) and in combination with rapamycin (Stage 2).
The dose-expansion (DE) portion will further optimize the dose and define the safety profile and preliminary efficacy of UB-VV400 alone and/or in combination with rapamycin. The study will use the Bayesian optimal interval (BOIN) design to allocate subjects to various DLs to minimize exposure to subtherapeutic DLs while maintaining appropriate safety parameters. DF will consist of 2 stages: Stage 1 DF aims to identify the MTD of UB-VV400 monotherapy, and Stage 2 DF aims to identify the MTD of UB-VV400 in combination with rapamycin. DF will be initiated in Stage 1 with UB-VV400 monotherapy, administered IV and starting at DL1.
Age ≥ 18 at time of consent.
Provide voluntary written informed consent.
Relapsed/refractory disease for subjects that are either CAR T-naive or CAR T-exposed.
Measurable disease according to Lugano 2014 criteria.
Women who are pregnant or breastfeeding.
Subjects with current isolated central nervous system (CNS) tumor involvement.
Subjects with a prior malignancy whose clinical course or management has the potential to interfere with the safety and/or efficacy evaluation of the clinical trial.
Prior treatment with any of the following: allogeneic bone marrow transplantation, gene therapy, or adoptive cell transfer of any kind except for CAR T-cell therapy.
Single group
UB-VV400
GeneticUB-VV400 is a third-generation, self-inactivating (SIN), replication-incompetent, lentiviral vector (LVV) investigational drug product
Rapamycin
DrugIn DF Stage 2, Rapamycin will be given in combination with UB-VV400. For subjects receiving rapamycin, rapamycin dosing will be once daily with a planned start date of Day 4 (approximately 72 hours after the administration of UB-VV400) and continuing for up to 60 days, as tolerated.
Number of participants with adverse events as assessed by CTCAE v5.0
Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities
Maximum tolerated dose (MTD) or maximum administered dose (MAD) of UB-VV400 alone and in combination with rapamycin.
Objective response rate (ORR) per the Investigator using the Lugano 2014 criteria.
Quantification of Immune cell subset frequencies (T/B/NK cells)
Complete response (CR) rate, as determined by the Investigator using the Lugano 2014 criteria.
Durability of response (DOR), the duration of response for subjects who acheived PR and CR as determined by the Investigator using the Lugano 2014 criteria.
Progression-free survival (PFS) and Overall survival (OS).
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Nanjing IASO Biotechnology Co., Ltd.
Lead sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborator
