A Study of CAR-GPRC5D in Patients With Relapsed/Refractory Multiple Myeloma or Plasma Cell Leukemia

NCT05219721 | Recruiting Phase 1

• 1 other identifier: RD138CI001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, open-label, dose-exploration study to observe the safety and efficacy of different doses of CAR-GPRC5D in patients with R/R MM or plasma cell leukemia.

Conditions

Relapsed/Refractory Multiple Myeloma; Plasma Cell Leukemia

Keywords

CAR-T; GPRC5D

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicity (DLT) by dose group

  Dose limiting toxicity will be assessed after infusion in each dose group

  28 days after CAR-T cell infusion

• Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group

  Calculate type and incidence of adverse events (AE), serious adverse event (SAE), including those happened after lymphodepletion and after infusion, those related to study drug and lymphodepletion, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification (SOC), preferred term (PT), and severity

  2 years after CAR-T cell infusion

Secondary Outcomes (16)

• Objective response rate (ORR)

  2 years after CAR-T cell infusion

• Overall survival (OS)

  2 years after CAR-T cell infusion

• Duration of response (DOR) after administration

  2 years after CAR-T cell infusion

• Progression-free survival (PFS)

  2 years after CAR-T cell infusion

• Time to response (TTR)

  2 years after CAR-T cell infusion

Other Outcomes (2)

• Positive rate of human anti-CAR antibody

  2 years after CAR-T cell infusion

• Number of Participants with replication competent lentivirus (RCL)

  2 years after CAR-T cell infusion

Study Arms (1)

CAR-GPRC5D cells

EXPERIMENTAL

After lymphodepletion, CAR-GPRC5D will be administered as a single infusion.

Drug: CAR-T (CAR-GPRC5D)

Interventions

CAR-T (CAR-GPRC5D) DRUG

CAR-GPRC5D (RD118) is an individualized, gene-modified autologous T-cell immunotherapy product targeting GPRC5D that identifies and eliminates malignant and normal cells expressing GPRC5D. The CAR structure comprises a fully human single-domain antibody fragment (VHH) targeting GPRC5D, fused with intracellular co-stimulatory (4-1BB) and activation (CD3ζ) signaling domains.

CAR-GPRC5D cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy all the following criteria to be enrolled in the study:
• age 18 to 75 years old, male or female.
• 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;
• 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).
• The subjects should have measurable disease based on at least one of the following parameters:
• The proportion of primitive immature or monoclonal plasma cells detected by bone marrow cytology, bone marrow biopsy, or flow cytometry is ≥ 10%.
• Serum M-protein ≥ 0.5 g/dL. Urine M-protein ≥ 200 mg/24 hrs. 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.
• In subjects with extramedullary myeloma, if there are no other evaluable lesions, require extramedullary lesions with a maximum diameter of ≥2cm
• ECOG performance score 0-2.
• Estimated life expectancy ≥ 12 weeks.
• Subjects should have adequate organ function:
• 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).
• Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
• Renal function: Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subjects who are known to have GVHD or need long-term immunosuppressive therapy.
• 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.
• 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.
• Subjects with hypertension that cannot be controlled by medication.
• 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.
• 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.
• 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.
• Subjects with a history of organ transplantation.
• 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).
• Subjects participated in another interventional clinical study 1 months before signing the informed consent (ICF);
• 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).
• 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

Sponsors & Collaborators

• Chunrui Li: lead
• Nanjing IASO Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Related Publications (1)

• Pan M, Wang D, Xu J, Jin S, Wang Y, Tao Y, Liu Y, Ouyang W, Weng X, Yi H, Huang Y, Cao X, Li S, Zhang F, Zhang W, Li C, Mi JQ. Fully Human anti-GPRC5D CAR T-Cell Therapy RD118 Induces Durable Remissions in Relapsed/Refractory Multiple Myeloma. Blood. 2025 Oct 21:blood.2025030559. doi: 10.1182/blood.2025030559. Online ahead of print.

  PMID: 41118600 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Plasma Cell

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia

Study Officials

• Chunrui Li

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chunrui Li

CONTACT

86-13647233185; cunrui5650@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This study pre-defined three dose levels of 1.0×10\^6 CAR-T/Kg, 2.0×10\^6 CAR-T/Kg, 3.0×10\^6 CAR-T/Kg. Each dose level will enroll 3-6 subjects, and the estimated total number of subjects will be 9-18. This study is to observe the characteristics of dose-limiting toxicity (DLT), pharmacokinetics, pharmacodynamics, and immunogenicity of CAR-GPRC5D in different dose groups. And to preliminarily observe the efficacy in small samples of patients with R/R MM or Plasma cell leukemia and confirm the recommended phase II dose (RP2D).

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: February 2, 2022
• Study Start: March 17, 2022
• Primary Completion: September 1, 2025
• Study Completion: October 1, 2025
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

CN (1)