Sequential CAR-T therapy targeting BCMA and GPRC5D for relapsed or refractory multiple myeloma

Sequential CAR-T Cells Targeting BCMA/GPRC5D in Patients With Relapsed/ Refractory Multiple Myeloma

This will try sequential CAR-T cell therapy against BCMA and GPRC5D in people with relapsed or refractory multiple myeloma to see if it is safe and helps control the disease.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 21 Years to 90 Years
• Sex: All
• Sponsor: Essen Biotech (Academic / other)
• Drugs / interventions: CAR-T, chimeric antigen receptor, immunotherapy, CAR T
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07032129 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm Phase 1/2 study testing sequential CAR-T cell infusions that target BCMA, GPRC5D, or both in patients with relapsed or refractory multiple myeloma. Eligible patients undergo leukapheresis for autologous CAR-T manufacture, receive lymphodepleting chemotherapy, and then one or more CAR-T infusions at a single center in Beijing. The trial focuses primarily on safety, including monitoring for cytokine release syndrome and other toxicities, and also measures disease response, remission duration, and CAR-T cell persistence. The sponsor is Essen Biotech and enrollment is aimed at patients who have failed standard therapies.

Who should consider this trial

Good fit: Adults with relapsed or refractory multiple myeloma who have exhausted standard treatments, meet organ-function criteria (including acceptable liver, kidney, and cardiopulmonary parameters), and have an expected survival of at least three months are the intended candidates.

Not a fit: Patients with significant organ dysfunction, active uncontrolled infections, or tumors that lack BCMA or GPRC5D expression may not receive benefit from this therapy.

Why it matters

Potential benefit: If successful, this approach could produce deeper or longer remissions for patients whose myeloma no longer responds to standard treatments.

How similar studies have performed: BCMA-directed CAR-T therapies have produced high response rates in relapsed/refractory myeloma and GPRC5D-targeting therapies have shown encouraging early activity, while sequential or dual-target CAR-T approaches remain experimental.

Eligibility criteria

Inclusion Criteria:

* Expected survival time ≥3 months;
* Subjects with recurrent/refractory Multiple Myeloma who have failed standard treatment or lack effective treatment, Including but not limited to systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, IGG4-associated diseases, primary Sjogren's syndrome, rheumatoid arthritis, connective tissue disease-associated interstitial lung disease, immune thrombocytopenia, primary biliary cholangitis, etc.
* Histological evidence of non-suppurative destructive cholangitis and small bile duct destruction.
* Liver and kidney function, cardiopulmonary function meet the following requirements:
* Creatinine ≤1.5×ULN; (2) Electrocardiogram showed no clinically significant abnormal bands;
* Blood oxygen saturation \>91% in non-oxygen state;
* Total bilirubin ≤2×ULN; ALT and AST≤2.5 x ULN; ALT and AST abnormalities due to disease, such as liver infiltration or bile duct obstruction, were determined to be less than 5×ULN. If Gilbert syndrome is diagnosed, the total bilirubin index can be relaxed to ≤3.0×ULN and the direct bilirubin ≤1.5×ULN.
* No serious mental disorders;
* Can understand this test and has signed the informed consent.

Exclusion Criteria:

* Malignant tumors other than R/R AID disease in the 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
* Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference value range; Hepatitis C virus (HCV) Antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) Antibody positive; Syphilis positive;
* Serious heart disease, including but not limited to unstable angina, myocardial infarction or bypass or stent surgery (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmia;
* Systemic diseases that are deemed unstable by researchers: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment;
* Active or uncontrollable infections (except mild genitourinary and upper respiratory tract infections) that require systemic treatment within 7 days prior to administration;
* Pregnant or lactating women, and female subjects who plan pregnancy within 2 years after cell transfusion or male subjects whose partners plan pregnancy within 2 years after cell transfusion;
* Patients who received CAR-T therapy or other gene-modified cell therapy before screening;
* Participated in other clinical studies 1 month before screening;
* Evidence of central nervous system invasion during subject screening;
* Mental patients with depression or suicidal thoughts;
* Situations considered unsuitable for inclusion by other researchers.

Where this trial is running

Beijing, Beijing Municipality

• District One Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Rhoda M Smith, Phd

Conditions Multiple Myeloma; Multiple Myeloma in Relapse; Multiple Myeloma Progression; Multiple Myeloma, Refractory; Multiple myeloma; myeloma; Autoimmune Diseases; CAR-T