CAR-GPRC5D treatment for patients with relapsed or refractory multiple myeloma or plasma cell leukemia

An Exploratory Study of Fully Human Anti-GPRC5D Chimeric Antigen Receptor T Cells (CAR-GPRC5D) in Patients With Relapsed/Refractory Multiple Myeloma or Plasma Cell Leukemia

This study is testing a new CAR-T cell treatment called CAR-GPRC5D to see if it can help people with relapsed or hard-to-treat multiple myeloma or plasma cell leukemia.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Nanjing IASO Biotechnology Co., Ltd. (Industry-sponsored)
• Drugs / interventions: CAR T, chemotherapy, prednisone, CAR-T, cyclophosphamide, fludarabine
• Locations: 1 site (Shanghai)
• Trial ID: NCT05759793 on ClinicalTrials.gov

What this trial studies

This is a single-center, open-label, dose-escalation study designed to evaluate the safety and efficacy of CAR-GPRC5D in patients suffering from relapsed or refractory multiple myeloma or plasma cell leukemia. Participants will undergo apheresis to manufacture CAR-T cells, followed by lymphodepletion with fludarabine and cyclophosphamide. Afterward, they will receive a single infusion of CAR-GPRC5D at varying doses. The study will monitor participants for a minimum of two years post-infusion, with long-term follow-up for vector safety extending up to 15 years.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with relapsed or refractory multiple myeloma or plasma cell leukemia who have undergone at least three prior lines of therapy.

Not a fit: Patients who have not expressed GPRC5D on their tumor cells or those with less than three prior lines of therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat multiple myeloma or plasma cell leukemia.

How similar studies have performed: While CAR-T cell therapies have shown promise in treating various hematological malignancies, this specific approach targeting GPRC5D is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

Subjects must satisfy all the following criteria to be enrolled in the study:

1. age 18 to 75 years old, male or female.
2. Subjects have had at least 3 prior lines of therapy including chemotherapy based on proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs).

   According to the International Myeloma Working Group (IMWG) consensus (2016) standard on multiple myeloma, the disease has recurred, progressed or is refractory, or according to the IMWG consensus (2013) standard on plasma cell leukemia (Appendix 4), the disease appears relapse, progress or refractory;
3. Evidence of cell membrane GPRC5D expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue (e.g., bone marrow biopsies, or plasmacytoma).
4. The subjects should have measurable disease based on at least one of the following parameters:

   1. The proportion of primitive immature or monoclonal plasma cells detected by bone marrow cytology, bone marrow biopsy, or flow cytometry is ≥ 10%.
   2. Serum M-protein ≥ 10 g/L for IgG type, serum M-protein ≥ 5 g/L for other types, such as IgA, IgD, IgM, IgE.
   3. Urine M-protein ≥ 200 mg/24 hrs.
   4. For those whose Serum or Urine M-protein does not meet the measurable criteria but the light chain type, serum free light chain (sFLC) : involved sFLC level ≥ 10mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
   5. In subjects with extramedullary myeloma, if there are no other evaluable lesions, require extramedullary lesions with a maximum diameter of ≥2cm
5. ECOG performance score 0-2.
6. Estimated life expectancy ≥ 12 weeks.
7. Subjects should have adequate organ function:

   1. Hematology: Absolute neutrophil count (ANC) ≥1×10\^9 /L (prior use of growth factor support is permitted, but subjects must not have received supportive treatment within 7 days prior to laboratory examination); absolute lymphocyte count (ALC) ≥0.3×10\^9 /L; platelets ≥40×10\^9 /L (subjects must not have received blood transfusion support within 7 days prior to laboratory examination); hemoglobin ≥60 g/L (subjects must not have received transfusion of red blood cells \[RBC\] within 7 days prior to laboratory examination; the use of recombinant human erythropoietin is permitted).
   2. Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
   3. Renal function: Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
   4. Coagulation function: Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤1.5×ULN.
   5. SpO2 \> 91%.
   6. Left ventricular ejection fraction (LVEF) ≥ 50%.
8. The subject and his/her spouse agree to use an effective contraceptive tool or medication (excluding safety period contraception) for one year from the date of the subject's informed consent to the date of CAR T cell infusion.
9. Subject must sign the informed consent form approved by ethics board in person before starting any screening procedure.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subjects who are known to have GVHD or need long-term immunosuppressive therapy.
2. Subjects have received any anti-cancer treatment as follows:

   monoclonal antibody for treating multiple myeloma within 21 days before leukapheresis, or cytotoxic therapy or proteasome inhibitors within 14 days before leukapheresis, or immunomodulatory agents within 7 days before leukapheresis. or anti-tumor treatments other than those listed above within 30 days before leukapheresis.
3. Subjects who were receiving a used therapeutic dose of corticosteroid treatment (defined as prednisone or equivalent \> 20mg) within 7 days prior to screening, except for physiological alternatives, inhalation, or topical use.
4. Subjects with hypertension that cannot be controlled by medication.
5. Subjects with serious heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmias.
6. Subjects with systemic diseases that the investigator determined to be unstable include, but are not limited to, severe liver and kidney or metabolic diseases requiring medical treatment.
7. Subjects with second malignancies in addition to MM within the past 5 years before the screening, exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal or squamous cell skin carcinoma, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast after radical surgery.
8. Subjects with a history of organ transplantation.
9. Subjects have received major surgery within 2 weeks prior to leukapheresis or plan to receive surgery during the study or within 2 weeks after the study treatment (excluding local anesthesia).
10. Subjects participated in another interventional clinical study 1 months before signing the informed consent (ICF);
11. Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis collection (excluding # CTCAE grade 2 urogenital infection and upper respiratory infection).
12. Positive for any of the following tests:

    Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood; Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood; Human immunodeficiency virus (HIV) antibody; Cytomegalovirus (CMV) DNA; Treponema Pallidum antibody
13. Pregnant or lactating women.
14. Subjects with mental illness or consciousness disorder or disease of the central nervous system
15. Other conditions that researchers consider inappropriate for inclusion.

Where this trial is running

Shanghai

• Ruijin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine — Shanghai, China (Recruiting)

Conditions Relapsed/Refractory Multiple Myeloma; Plasma Cell Leukemia; GPRC5D; RRMM; PCL