Advanced Malignant Tumours
Conditions
Keywords
in vivo CAR-T, DLL3, GPRC5D, BCMA, FcRH5
Brief summary
This is a single-arm, open-label, single-center, dose-escalation Phase I platform study designed to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics, and pharmacodynamics of an in vivo CAR-T therapy (V001 Injection, targeting BCMA, GPRC5D, DLL3,FcRH5, etc.) in patients with advanced malignant tumors.
Detailed description
This is a single-arm, open-label, single-center, dose-escalation Phase I platform study designed to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics, and pharmacodynamics of an in vivo CAR-T therapy (V001 Injection, targeting BCMA, GPRC5D, DLL3, etc.) based on a lentiviral vector platform in patients with advanced malignant tumors (including hematological malignancies and solid tumors). The study employs a platform design, enrolling patients into different cohorts based on target and indication.
Interventions
GENETICV001-BCMA
An in vivo CAR-T drug targeting BCMA administered intravenously
GENETICV001-GPRC5D
An in vivo CAR-T drug targeting GPRC5D administered intravenously
GENETICV001-DLL3
An in vivo CAR-T drug targeting DLL3 administered intravenously
GENETICV001-FcRH5
An in vivo CAR-T drug targeting FcRH5 administered intravenously
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * Histologically confirmed advanced hematological malignancies (e.g., multiple myeloma, lymphoma) or solid tumors (e.g., small cell lung cancer) that are relapsed or refractory. * Tumor cells express the relevant target (e.g., BCMA, GPRC5D, DLL3) as required for the specific cohort. * ECOG performance status 0-2 (hematological malignancies) or 0-1 (solid tumors) and life expectancy ≥ 3 months. * Adequate organ function (e.g., creatinine clearance ≥45 mL/min, LVEF ≥45%). * Patients of childbearing potential must agree to use effective contraception during the study and for 1 year after dosing. * Signed informed consent form.
Exclusion criteria
* Active, uncontrolled infection. * Active central nervous system metastases or involvement. * Prior anticancer therapy, radiotherapy, or investigational therapy within specified timeframes before the first study dose. * Severe cardiac or pulmonary disease (e.g., NYHA Class III/IV heart failure), severe hepatic or renal impairment. * Active Hepatitis B, Hepatitis C, HIV, or syphilis infection. * Prior allogeneic hematopoietic stem cell transplantation (within specified window) or active graft-versus-host disease. * Pregnancy or lactation. * History of severe allergy to any components of the investigational product. * Any other condition deemed by the investigator to increase risk or interfere with study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | Within 28 days after the first infusion | Incidence and characteristics of DLTs graded according to NCI CTCAE v5.0. The DLT observation period is 28 days post-infusion. |
| Maximum Tolerated Dose (MTD) | During the dose-escalation phase (approximately 12 months) | To determine the MTD of V001 Injection. |
| Incidence of Adverse Events (AEs) | From signing ICF until 24 months after the last infusion. | Incidence and severity of treatment-emergent adverse events (TEAEs) graded according to NCI CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | At Day 28, Months 2, 3, 6, 9, 12, 18, 24 post-infusion | Best overall response rate assessed per indication-specific criteria. |
| Duration of Response (DOR) | From date of the first response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | Time from first achieving response to disease progression or death. |
| Progression-Free Survival (PFS) | From date of infusion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | From date of infusion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months |
| Overall Survival (OS) | From the date of infusion until the date of death from any cause, assessed up to 24 months | Time from infusion to death from any cause |
| Peak concentration of CAR-T cells in peripheral blood | At multiple timepoints post-infusion up to Month 24 | Peak concentration of CAR-T cells in peripheral blood |
| time to peak of CAR-T cells in peripheral blood | At multiple timepoints post-infusion up to Month 24 | time to peak of CAR-T cells in peripheral blood |
| AUC of CAR-T cells in peripheral blood | At multiple timepoints post-infusion up to Month 24 | AUC of CAR-T cells in peripheral blood |
Countries
China
Contacts
CONTACTLi Ning, M.D.
CONTACTShuhang Wang, PhD
STUDY_DIRECTORShuhang Wang, PhD
Clinical Trial Center
Outcome results
None listed