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

NCT ID: NCT06743503

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-11
• Study Completion Date: 2030-07-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment group

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 .

Group Type: EXPERIMENTAL

UB-VV400

Intervention Type: GENETIC

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

Rapamycin

Intervention Type: 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.

Interventions

UB-VV400

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

Intervention Type: GENETIC

Rapamycin

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 at time of consent.

2. Provide voluntary written informed consent.

3. Relapsed/refractory disease for subjects that are either CAR T-naive or CAR T-exposed.

4. Measurable disease according to Lugano 2014 criteria.

5. No serious concomitant diseases or active/uncontrolled infections.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

7. Cardiac function: left ventricular ejection fraction (LVEF) ≥ 40%.

8. Pulmonary function: pulse oximetry ≥ 90% on room air at rest.

9. Renal function: serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) or creatinine clearance ≥ 45 mL/min.

10. Absolute lymphocyte count (ALC) ≥ 0.2×10^9/L.

11. Alanine aminotransferase (ALT) ≤ 2.5 × ULN, aspartate aminotransferase (AST) ≤ 2.5 × ULN, AND total bilirubin < 1.5 × ULN.

12. No ongoing coagulopathies requiring periodic replacement of clotting factors (eg, fresh frozen plasma, cryoprecipitate).

13. Women of childbearing potential must:

1. 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).

2. 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 .

3. Abstain from breastfeeding for 12 months following administration of UB-VV400.

14. 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.

15. 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.

Exclusion Criteria

1. Women who are pregnant or breastfeeding.

2. Subjects with current isolated central nervous system (CNS) tumor involvement.

3. 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.

4. 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.

5. Treatment with prior CD22-directed therapy except for UB-VV400.

6. History of or active human immunodeficiency virus (HIV).

7. Active hepatitis B (HepB) or hepatitis C (HepC).

8. For subjects receiving rapamycin: a. History of angioedema; b. Pneumonitis (Grade 3 or greater).

9. Ongoing Grade > 2 toxicities from the last line of anticancer therapy.

10. Use of the following:

1. Therapeutic systemic doses of corticosteroids (defined as > 20 mg prednisone equivalent) within 72 hours before dosing with UB-VV400.

2. 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).

g. Radiation within 4 weeks before dosing with UB-VV400 (palliative radiation to a symptomatic lesion[s] is allowed if at least one additional, non-irradiated, measurable lesion remains present to assess response).

h. Prophylactic treatment with short-acting oral antiretroviral medications within 7 days before UB-VV400 administration. Long-acting antiretroviral prophylaxis is not allowed within 2 years of UB-VV400 treatment.

11. Allergies to rapamycin or supportive medications required for CAR T-cell toxicity management (eg, tocilizumab).

12. Systemic autoimmune diseases or immunodeficiency diseases (except for well-controlled type I diabetes with hemoglobin A1C [HbA1c] less than 8% or well-controlled thyroid disease, as assessed by the treating physician).

13. Ongoing CNS diseases (eg, seizure disorder, tremor, history of cerebral vascular accident [CVA]/recurrent transient ischemic attack [TIA]) that would preclude evaluation of immune effector cell-associated neurotoxicity syndrome (ICANS).

14. Presence of uncontrolled angina or other acute uncontrolled heart disease. Myocardial infarction within the previous 6 months. New York Heart Association (NYHA) Class III or IV. History of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

15. Actively receiving treatment in other interventional clinical trials. Note: continued follow-up on previous trials is allowed for survivorship, but no further investigational agents or assessments will be allowed.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: collaborator

Nanjing IASO Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lei Fan

Role: PRINCIPAL_INVESTIGATOR

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

Locations

The First Affiliated Hospital of Nanjing Medical University

Nanjing, , China

Site Status: RECRUITING

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

Tianjin, , China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Changpu Cao

Role: CONTACT

changpu.cao@iasobio.com

+86-13584069411

Facility Contacts

Lei Fan

Role: primary

Liang Huang

Role: primary

Dehui Zou

Role: backup

Other Identifiers

UB-VV400CI001

Identifier Type: -

Identifier Source: org_study_id