Dual-target BCMA and GPRC5D CAR-T for relapsed/refractory multiple myeloma with extramedullary disease

Practical Clinical Study of Dual-targeting BCMA-GPRC5D CAR-T Cell Therapy for Extramedullary Infiltration in Refractory/Relapsed Multiple Myeloma

This will try a CAR-T cell treatment that targets both BCMA and GPRC5D for adults whose relapsed or refractory multiple myeloma has spread outside the bone marrow.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing GoBroad Hospital (other)
• Drugs / interventions: cyclophosphamide, fludarabine, CAR-T
• Locations: 1 site (Shanghai)
• Trial ID: NCT07003568 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, single-arm Phase 1 study enrolling up to 18 patients with relapsed or refractory multiple myeloma and measurable extramedullary lesions. Eligible patients must have tumor cells positive for BCMA and GPRC5D and adequate organ function before leukapheresis and CAR-T cell reinfusion. Participants will receive an infusion of dual-target BCMA-GPRC5D CAR-T cells and be closely monitored for safety, with a primary focus on dose-limiting toxicities and adverse events within one month after reinfusion. The study is primarily designed to characterize the safety profile of the dual-target CAR-T approach in this high-risk patient group.

Who should consider this trial

Good fit: Adults 18–75 years old with relapsed or refractory multiple myeloma, measurable extramedullary lesions, tumor cells positive for BCMA and GPRC5D, and adequate cardiac, liver, renal, coagulation, oxygenation, and pulmonary function are ideal candidates.

Not a fit: Patients without extramedullary disease, whose tumor cells do not express BCMA and GPRC5D, or who have insufficient organ function or other contraindications are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, this therapy could provide a targeted option that helps control disease outside the bone marrow for patients who have limited treatment choices.

How similar studies have performed: BCMA-directed CAR-T therapies have produced strong responses in many relapsed myeloma patients but extramedullary disease is harder to treat, and dual-targeting with GPRC5D is a newer, investigational strategy with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participate in the trial and have good compliance.
2. Aged between 18 and 75 years old, regardless of gender.
3. Diagnosed with relapsed or refractory multiple myeloma according to the criteria of the International Myeloma Working Group (IMWG)2, and have measurable extramedullary lesions due to multiple myeloma.
4. Positive for BCMA and GPRC5D in flow cytometry of bone marrow or cerebrospinal fluid tumor cells or immunohistochemistry of tumor tissue.
5. Organ functions: ① Cardiac function: Left ventricular ejection fraction \> 50% (by echocardiogram) in the past 2 weeks. ② Liver function: Alanine aminotransferase and aspartate aminotransferase \< 3 times the upper limit of normal (ULN). ③ Renal function: Creatinine clearance rate ≥ 40 mL/min (by Cockcroft and Gault formula). ④ Coagulation function: PT and APPT \< 1.5 times the ULN. ⑤ Arterial oxygen saturation (SpO₂) \> 95%. ⑥ Pulmonary function: FEV₁% predicted value ≥ 50%.
6. Female patients of childbearing age must have a negative serum pregnancy test at screening and before receiving cyclophosphamide and fludarabine or melphalan treatment; male patients should be willing to use effective contraceptive methods for 1 year after receiving the study treatment.
7. ECOG score ≤ 2.
8. Expected survival time \> 3 months.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Active infections that have not been effectively controlled.
3. Active autoimmune diseases that have not been effectively controlled.
4. Adverse reactions caused by previous treatments have not recovered to CTCAE grade ≤ 1.
5. For allogeneic transplant patients, active graft - versus - host disease (GVHD) that has not been effectively controlled.
6. Presence of any of the following: HBV - DNA copy number above the lower limit of detection; positive hepatitis C antibody (HCV - Ab) with HCV - RNA copy number above the lower limit of measurability; positive anti - Treponema pallidum antibody (TP - Ab); positive human immunodeficiency virus (HIV) antibody test.
7. Allergic or intolerant to fludarabine or cyclophosphamide.
8. Suffering from known symptomatic non - plasma cell infiltrative central nervous system diseases.
9. Uncontrollable cardiovascular and cerebrovascular diseases within 6 months, such as: a. New York Heart Association (NYHA) class III or IV congestive heart failure. b. Myocardial infarction occurred or coronary artery bypass grafting (CABG) was received ≤ 6 months before enrollment. c. Clinically significant ventricular arrhythmia or a history of unexplained syncope (excluding cases caused by vasovagal or dehydration). d. A history of severe non - ischemic cardiomyopathy.
10. A history of other untreated malignancies within the past 5 years or having other untreated malignancies concurrently.
11. The investigator assesses that the subject cannot or is unwilling to comply with the requirements of the study protocol.
12. Previous use of a CAR - T vector with the same structure.

Where this trial is running

Shanghai

• Shanghai Liquan Hospital — Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Yao Yao

Conditions: Relapsed or Refractory Multiple Myeloma