Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of R/RMM

Phase 1

Recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Nanobody-based biepitope BCMA-targeting CAR-T cells

• Registration Number: NCT06503107
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

To explore the safety and efficacy of nanobody-based BCMA-targeting biepitope CAR-T cells in the treatment of relapsed/refractory multiple myeloma，this study will be conducted in multiple study centers, with 60 patients openly enrolled to receive CAR-T cell therapy. Patients participating in clinical trials will be tested and evaluated for treatment safety, efficacy, duration of response, and long-term survival.

Detailed Description

This study is a multicenter, open-label, prospective, single-arm clinical study with patients with relapsed/refractory multiple myeloma as the test subjects, in order to evaluate the safety and efficacy of nanobody-based biepitope CAR-T cells targeting BCMA in the treatment of R/RMM, and to collect CAR-T PK/PD indicators. The structure of BCMA target CAR-T is designed to identify two different epitopes of BCMA protein with two recognition domains, in order to killig MM cells without secreting more pro-inflammatory factors and avoiding escape caused by the limitations of single BCMA antigen recognition.

Study Timeline

• Study Start: 2024-04-23
• Study First Submitted: 2024-06-17
• Status Verified: 2024-07
• Study First Submitted QC: 2024-07-09
• Last Update Submitted: 2024-07-09
• Study First Posted: 2024-07-16
• Last Update Posted: 2024-07-16
• Primary Completion: 2026-04-18
• Study Completion: 2026-10-18

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

• Aged ≥ 18 years and ≤ 75 years.

• Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG 2014).

• Diagnosed as relapsed/refractory disease or primary refractory disease; relapse is defined as disease progression within 60 days of the most recent treatment with three or more lines of therapy with different mechanisms of action; refractory is defined as failure to achieve MR or above efficacy with prior treatment and disease progression with recent treatment, or disease progression within 60 days of treatment.

• Flow cytometry or immunohistochemistry showed positive BCMA expression in myeloma cells.

• Have not been treated with antibody-based drugs within 2 weeks prior to cell therapy.

• ECOG score 0-2 points.

• HGB≥70g/L，PLT≥30×10^9/L.

• Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Serum creatinine ≤ 1.5× ULN or creatinine clearance (Cockcroft-Gault) >30 ml/min；
  2. Left ventricular ejection fraction (LVEF) ≥50%,
  3. Baseline peripheral oxygen saturation > 90%;
  4. Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN.

Exclusion Criteria

• Previous diagnosis and treatment of other malignancies within 3 years;
• Presence of one of the following cardiac criteria: atrial fibrillation; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary QT prolongation, as judged by the investigator. Echocardiogram LVSF <30% or LVEF <50%; Clinically significant pericardial effusion; Cardiac insufficiency NYHA (New York Heart Association) III or IV (absence of this symptom confirmed by echocardiography within 12 months of treatment);
• Patients with active GVHD;
• Patients with a history of severe pulmonary impairment disease;
• Combined with other malignant tumors in the advanced stage;
• Co-infection with severe or persistent infection that cannot be effectively controlled;
• Combined with severe autoimmune disease or congenital immunodeficiency;
• Active hepatitis (hepatitis B virus deoxyribonucleic acid [HBV-DNA ≥ 500 IU/ml and abnormal liver function] or hepatitis C antibody [HCV-Ab] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function);
• Human immunodeficiency virus (HIV) infection or syphilis infection;
• Patients with a history of severe allergy to biological products (including antibiotics);
• Patients with central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc;
• Pregnant or Lactating Women; Patients and his or her spouses have a fertility plan within 12 months after CAR-T cell infusion;
• Other conditions considered inappropriate by the researcher.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Effective of nanobody-based biepitope BCMA-targeting CAR-T cells	Nanobody-based biepitope BCMA-targeting CAR-T cells	The recommended reinfusion dose of biepitope BCMA-targeting CAR-T cells in this trial is: 1 × 10\^6/kg, 2 × 10\^6/kg CAR-T cells.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM	within 3 years after infusion	Disease overall response rate (ORR) will be assessed from CAR-T cell infusion to death or last follow-up (censored).; The rates of stringent complete response (sCRs), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR) will be assessed from CAR T cell infusion to death or last follow-up (censored). ORR will be assessed from CAR T cell infusion to death or last follow-up.
Incidence of Treatment-related Adverse Events	within 3 years after infusion	Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
The rates of complete response (CR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM	within 3 years after infusion	CR will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Very good partial response (VGPR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM	within 3 years after infusion	VGPR will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Partial response rate (PR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM	within 3 years after infusion	PR will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Stable diseases (SD) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM	within 3 years after infusion	SD will be assessed from CAR-T cell infusion to death or last follow-up (censored).

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma	within 3 years after infusion	OS will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Progression-free survival (PFS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma	within 3 years after infusion	PFS will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Event-free survival (EFS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma	within 3 years after infusion	EFS will be assessed from CAR-T cell infusion to death or last follow-up (censored).

Trial Locations

Locations (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China