An Exploratory, Open-label Study of UB-VV400 in Combination With Rapamycin in Relapsed or Refractory B-cell Malignancies
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.
• No serious concomitant diseases or active/uncontrolled infections.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Cardiac function: left ventricular ejection fraction (LVEF) ≥ 40%.
• Pulmonary function: pulse oximetry ≥ 90% on room air at rest.
• Renal function: serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) or creatinine clearance ≥ 45 mL/min.
⁃ Absolute lymphocyte count (ALC) ≥ 0.2×10\^9/L.
⁃ Alanine aminotransferase (ALT) ≤ 2.5 × ULN, aspartate aminotransferase (AST) ≤ 2.5 × ULN, AND total bilirubin \< 1.5 × ULN.
⁃ No ongoing coagulopathies requiring periodic replacement of clotting factors (eg, fresh frozen plasma, cryoprecipitate).
⁃ Women of childbearing potential must:
∙ Have 2 negative pregnancy tests verified (one negative serum beta human chorionic gonadotropin \[β-hCG\] at screening and another within 48 hours prior to treatment withUB-VV400).
‣ Commit to true abstinence from heterosexual intercourse or agree to use and complywith highly effective, uninterrupted contraception for 12 months after administration of UB-VV400 .
‣ Abstain from breastfeeding for 12 months following administration of UB-VV400.
⁃ Men with partners of childbearing potential must commit to true abstinence from heterosexual intercourse or agree to use a highly effective form of contraception duringheterosexual contact with a pregnant individual or any individual of childbearing potential for 12 months after administration of UB-VV400, regardless of past vasectomy.
⁃ Subjects must agree not to donate blood, organs, sperm/semen, and/or egg cells for use for at least 1 year following treatment with UB-VV400 alone or in combination with rapamycin. Insufficient data are available to define a duration of time sufficient to make a recommendation on when it is safe to donate any tissue; therefore, subjects should not donate any tissue after administration of UB-VV400.