UB-VV400 in Combination With Rapamycin in Relapsed or Refractory B-cell Malignancies

NCT06743503 | Recruiting Phase 1

• 1 other identifier: UB-VV400CI001
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Large B-cell Lymphoma

Keywords

UB-VV400; relapsed or refractory; Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events as assessed by CTCAE v5.0

  Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities

  up to 24 months

• Maximum tolerated dose (MTD) or maximum administered dose (MAD) of UB-VV400 alone and in combination with rapamycin.

  up to 24 months

Secondary Outcomes (1)

• Objective response rate (ORR) per the Investigator using the Lugano 2014 criteria.

  up to 24 months

Other Outcomes (13)

• Quantification of Immune cell subset frequencies (T/B/NK cells)

  up to 24 months

• Complete response (CR) rate, as determined by the Investigator using the Lugano 2014 criteria.

  up to 24 months

• 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.

  up to 24 months

Study Arms (1)

treatment group

EXPERIMENTAL

Interventions: UB-VV400 with or without Rapamycin. Dosage and Administration:single dose of UB-VV400 intravenous injection at Day 1. For subjects receiving rapamycin, dosing should be planned to be initiated on Study Day 4 and continued for up to 60 days, as tolerated .

Genetic: UB-VV400; Drug: Rapamycin

Interventions

UB-VV400 GENETIC

UB-VV400 is a third-generation, self-inactivating (SIN), replication-incompetent, lentiviral vector (LVV) investigational drug product

treatment group

Rapamycin DRUG

In 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.

treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 .

You may not qualify if:

• 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.
• Treatment with prior CD22-directed therapy except for UB-VV400.
• History of or active human immunodeficiency virus (HIV).
• Active hepatitis B (HepB) or hepatitis C (HepC).
• For subjects receiving rapamycin: a. History of angioedema; b. Pneumonitis (Grade 3 or greater).
• Ongoing Grade \> 2 toxicities from the last line of anticancer therapy.
• Use of the following:
• Therapeutic systemic doses of corticosteroids (defined as \> 20 mg prednisone equivalent) within 72 hours before dosing with UB-VV400.
• Approved targeted therapies:
• i. Small molecules: within 3 half-lives before dosing with UB-VV400 (see package insert). ii. Antibodies: within 14 days before dosing with UB-VV400. iii. CAR T therapy: within 28 days before dosing with UB-VV400. c. Autologous stem cell transplant within 28 days before dosing with UB-VV400. d. Cytotoxic chemotherapy (eg, alkylators, anthracyclines) within 14 days before dosing with UB-VV400.
• e. Any experimental agent (ie, not approved for disease/indication or with accepted consensus guidelines recommendation) within 4 weeks before dosing with UB-VV400 unless progression has been documented and a minimum of 3 half-lives has elapsed.
• f. Any immune-suppressing agent within 28 days before dosing with UB-VV400 (eg, tacrolimus, mycophenolate mofetil, immunosuppressive antibodies such as anti-tumor necrosis factor \[TNF\]/IL-6).

Sponsors & Collaborators

• Nanjing IASO Biotechnology Co., Ltd.: lead
• The First Affiliated Hospital with Nanjing Medical University: collaborator

Study Sites (2)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, China

RECRUITING

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, China

NOT YET RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Lei Fan

  Department of Hematology, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Changpu Cao

CONTACT

+86-13584069411; changpu.cao@iasobio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: December 20, 2024
• Study Start: April 11, 2025
• Primary Completion (Estimated): May 21, 2028
• Study Completion (Estimated): July 31, 2030
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)