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This is a prospective, single-arm, open-label, early exploratory clinical study designed to evaluate the safety, tolerability, and efficacy of the DQ1001 cell product in patients with relapsed or refractory multiple myeloma. All participants will receive intravenous infusions of DQ1001. The study consists of two phases: dose escalation and dose expansion. Following identification of an optimal dose during the dose-escalation phase, the cohort receiving that dose will be expanded to include a total of 12 participants-including those enrolled during dose escalation-to further assess the safety, tolerability, and efficacy of DQ1001.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DQ1001 Treatment Group | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic, off-the-shelf CAR-T cell injection targeting BCMA and GPRC5D | Biological | Patients received fludarabine and cyclophosphamide lymphodepleting preconditioning for three consecutive days-from day -5 (D-5) to day -3 (D-3)-prior to intravenous infusion of DQ1001. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Dose-limiting Toxicity (DLT) | DLT refers to drug-related toxicities that occur during treatment, the severity of which is clinically unacceptable, thereby restricting further dose escalation. All adverse events are assessed and graded by the investigator according to the NCI-CTCAE version 6.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are graded per the ASTCT criteria, and acute graft-versus-host disease (aGVHD) per the MAGIC criteria. | Within 28 days after the infusion of DQ1001 |
| Number of Participants with Adverse Events (AEs) by Severity | An adverse event is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are graded per the ASTCT criteria, and acute graft-versus-host disease (aGVHD) per the MAGIC criteria. | Up to 2 years |
| Establish recommended Phase 2 dose (RP2D) | Up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| efficacy endpoint: Overall response rate (ORR) | Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24 | |
| efficacy endpoint: Duration of Response (DoR) | Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24 |
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Inclusion Criteria:
Voluntary signing of the Informed Consent Form (ICF) prior to undergoing any study-related procedures.
Age at the time of ICF signing is between 18 and 70 years inclusive.
Diagnosis of relapsed or refractory multiple myeloma (MM), per IMWG criteria:
Prior receipt of at least three lines of therapy;
Tumor cells in bone marrow or peripheral blood are BCMA/GPRC5D-positive by flow cytometry; or tumor tissue is BCMA/GPRC5D-positive by immunohistochemistry.
Presence of measurable disease at screening, defined as any one of the following:
ECOG performance status score of 0-2.
Expected survival ≥12 weeks.
Men with reproductive potential and women of childbearing potential must agree to use effective contraception from the time of ICF signing through two years after the last dose of study drug. Women of childbearing potential include premenopausal women and women within two years of menopause. A negative serum pregnancy test is required at screening for women of childbearing potential.
For patients who previously underwent hematopoietic stem cell transplantation: no active graft-versus-host disease (GVHD), and systemic immunosuppressants discontinued for at least four weeks.
Adequate major organ function, defined as follows:
Investigator judgment that the participant is able to comply with protocol requirements and complete treatment and follow-up.
Exclusion Criteria:
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| efficacy endpoint: MRD negativity rate | Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24 |
| efficacy endpoint: Time to response (TTR) | Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24 |
| efficacy endpoint: progression-free survival (PFS) | Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24 |
| Efficacy endpoint: Overall survival (OS) | Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24 |
| Concentration of CAR-T cells after Infusion (PK) | Flow cytometry is used to determine the percentage and absolute count of CAR-T cells in peripheral blood, and polymerase chain reaction (PCR) is used to measure CAR copy numbers. | Up to 2 years |
| Lymphocyte Subsets and Concentration of Cytokine after Infusion (PD) | Assessment of lymphocyte subsets (CD3+ T cells, CD4+ cells, CD8+ cells, etc.), CAR-T-related cytokines (IL-6, IL-8, IL-10, IL-2R, TNF-α, IFN-γ, IL-1β, ferritin, C-reactive protein, etc.), as well as CAR-T cell subset analysis and exhaustion markers. | Up to 2 years |
| Anti-DQ1001 antibodies in peripheral blood | Up to 2 years |