A Clinical Study to Evaluate the Safety and Efficacy of ESO-T01 in Treating Relapsed/Refractory Multiple Myeloma.

This is a single center, single arm, open-label, dose escalation, phase 1 study to evaluate the safety, tolerability, preliminary efficacy and immunogenicity of ESO-T01 for patients with relapsed/refractory multiple myeloma.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: ESO-T01 Injection

Detailed Description

This investigator-initiated clinical study aims to evaluate ESO-T01, the third-generation self-inactivating lentiviral vector that carries a BCMA-targeted CAR, in patients with relapsed refractory multiple myeloma (MM). The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Heng Mei, Ph.D&M.D; Phone Number: 027-8572600; Email: hmei@hust.edu.cn
      • Contact: Jia Xu, Ph.D; Phone Number: 18274201261; Email: xu_jia@hust.edu.cn
      • Contact: Heng Mei, Ph.D&M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years；
2. Diagnosis of multiple myeloma (MM) confirmed according to the IMWG diagnostic criteria, with BCMA expression on MM cells determined by flow cytometry or pathology immunohistochemistry;
3. Previously treated with at least 2 lines of anti-MM therapy, with at least 1 complete treatment cycle for each line, and evidence of disease progression within 12 months after the most recent anti-myeloma treatment, or being refractory to both immunomodulatory drugs and proteasome inhibitors, with disease progression within 2 months after the most recent anti-myeloma treatment (according to the IMWG diagnostic criteria);
4. Disease must be measurable at screening, meeting at least one of the following criteria:Serum M-protein level ≥ 0.5 g/dL; Urinary M-protein level ≥ 200 mg/24h; Serum involved free light chain ≥ 10 mg/dL and an abnormal serum free light chain κ/λ ratio; clinical relapse: a. New bone lesions or soft tissue plasmacytomas (excluding osteoporotic fractures); b. Confirmed increase (≥ 50% increase in SPD of measurable lesions with an absolute value of ≥ 1 cm) in pre-existing plasmacytomas or bone lesions.
5. ECOG score 0-2, with an expected survival time ≥ 3 months;
6. Bone marrow function at screening (or within 2 months prior to screening) meets the following criteria: a.Hemoglobin ≥ 6 g/dL (no red blood cell transfusion within 1 week before screening), recombinant human erythropoietin is allowed; for patients who meet the ≥6 g/dL criterion at screening, red blood cell transfusion is allowed to maintain hemoglobin ≥ 6 g/dL; b.Absolute neutrophil count (ANC) ≥ 600/μL (no use of granulocyte colony-stimulating factor (G-CSF) within 1 week or pegylated G-CSF within 2 weeks prior to screening); c. Platelet count ≥ 50,000/μL; d. Lymphocyte count ≥ 500/μL; e. Absolute CD3-positive T cell count ≥ 150/μL;
7. Renal function at screening (or within 2 months prior to screening) should be normal, with a creatinine clearance ≥ 45 mL/min;
8. Liver function at screening (or within 2 months prior to screening) must meet the following criteria: a. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × the upper limit of normal (ULN); b. Total bilirubin (TBIL) and alkaline phosphatase (AKP or ALP) ≤ 2.0 × ULN (except for congenital hyperbilirubinemia, such as Gilbert's syndrome, where direct bilirubin can be ≤ 1.5 × ULN); c. Albumin ≥ 3 g/dL;
9. Cardiac function at screening (or within 2 months prior to screening) must meet the following criteria: a. Left ventricular ejection fraction ≥ 40% (measured by echocardiogram or MUGA scan); b. No clinically significant pericardial effusion detected; c. No clinically significant ECG abnormalities detected;
10. Pulmonary function at screening (or within 2 months prior to screening) must meet the following criteria: Oxygen saturation ≥ 90%;No clinically significant pleural effusion detected;
11. For women of childbearing potential, a negative pregnancy test must be obtained at screening and prior to drug infusion, and they must not be breastfeeding;
12. Male and female subjects of childbearing potential must agree to use effective contraception from the time of informed consent until 1 year after the study drug administration;
13. Male and female subjects of childbearing potential must agree not to donate sperm or eggs (oocytes) or other reproductive cells from the time of informed consent until 1 year after the study drug administration;
14. The participant or their legally authorized representative must provide written informed consent (ICF), indicating their understanding of the purpose and procedures of the study and their willingness to participate.

Exclusion Criteria:

1. Previous anticancer treatment (as determined by the investigator): a. Received targeted therapy, epigenetic therapy, other investigational drugs, or treatment using invasive investigational medical devices within 5 half-lives; b. Received immune/non-immune-directed systemic therapy within 1 week; Received cytotoxic therapy within 1 week; c. Received proteasome inhibitors or immunomodulatory agent therapy within 2 weeks; d. Received radiotherapy within 4 weeks (if the radiation field covered ≤5% of bone marrow reserve, the subject is eligible regardless of the date of radiotherapy completion);
2. Received allogeneic HSCT within 6 months prior to infusion, or autologous HSCT within 3 months prior to infusion;
3. Other malignancies prior to screening (except the following): Malignancies treated with curative intent and no evidence of active disease ≥2 years before enrollment; Adequately treated non-melanoma skin cancer with no evidence of disease;
4. Previously treated with any viral therapy using VSVG pseudotype virus;
5. Serious uncontrolled infections during screening: Bacterial, viral, fungal, etc. infections;
6. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with elevated peripheral blood HBV DNA levels within 6 months prior to infusion; Positive for hepatitis C antibody (HCV Ab) with elevated peripheral blood HCV RNA levels; Positive for HIV antibody; Positive for syphilis;
7. Symptomatic heart failure or significant arrhythmias: NYHA Class III or IV congestive heart failure; Myocardial infarction or coronary artery bypass grafting (CABG) or coronary stent implantation within ≤6 months prior to signing ICF; Clinically significant ventricular arrhythmias or unexplained syncope (except when caused by vasovagal or dehydration); Significant non-ischemic cardiomyopathy history;
8. Other significant diseases: Primary immunodeficiency; Stroke or seizure within 6 months prior to screening; Obvious clinical evidence of dementia or altered mental status; History of Parkinson's disease or Parkinsonism;
9. Surgery within 2 weeks prior to treatment or planned surgery within 2 weeks post-treatment, except for local anesthesia procedures;
10. Use of live-attenuated vaccines within 1 month before treatment;
11. Known severe allergic reaction to ESO-T01 or its formulation components;
12. Known severe allergic reaction to Tocilizumab;
13. Inability to establish venous access;
14. Any other condition deemed by the investigator as unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ESO-T01 Injection; ESO-T01 Injection is one kind of third-generation non-replicative self-inactivating lentivirus vector which carries an effective BCMA-targeted CAR. ESO-T01 can be administered intravenously and produce CAR-T in vivo.	Drug: ESO-T01 Injection; ESO-T01 Injection is one kind of third-generation non-replicative self-inactivating lentivirus vector which carries an effective BCMA-targeted CAR. ESO-T01 can be administered intravenously and produce CAR-T in vivo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine release syndrome (CRS)	Cytokine release syndrome (CRS) would be graded according to the ASTCT consensus.	up to Day 28 post-infusion
Dose-limiting toxicities (DLTs)		Dose-limiting toxicities (DLTs) are evaluated between the infusion and 28 days post-infusion.
immune cell-associated immune effector cell-associated neurotoxicity syndrome (ICANS)	ICANS would be scored according to Immune Effector Cell-Associated Encephalopathy (ICE), and then graded by the ASTCT consensus.	up to Day 28 post-infusion
Treatment-associated adverse effects (AEs)	All other AEs would be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).	up to 2 years after treatment of ESO-T01

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Clinical efficacy can be evaluated according to the 2016 International Myeloma Working Group consensus criteria.	Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01.
Complete response (CR) rate	sCR/CR can be evaluated according to the 2016 International Myeloma Working Group consensus criteria.	Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01.
Duration of response (DOR)	DOR is defined as the interval between the first sCR, CR, VGPR, or PR after infusion and the disease progression or death.	Through study completion, an average of 2 year
Progression-free survival (PFS)	PFS is defined as the interval between a subject's receipt of ESO-T01 infusion and the first assessment of disease progression or death.	up to 2 years after treatment of ESO-T01.
Overall survival (OS)	OS is defined as the interval between a subject's receipt of ESO-T01 infusion and death from any cause.	up to 2 years after treatment of ESO-T01
Cmax	CAR-T kinetics would be detected by flow cytometry and droplet digital PCR in peripheral blood and bone marrow at each important time points. Cmax is the peak expansion value of CAR-T cells.	Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01
Tmax	CAR-T kinetics would be detected by flow cytometry and droplet digital PCR in peripheral blood and bone marrow at each important time points. Tmax is the time of the occurrence of expansion peak.	Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01
AUC(0-day 28)	CAR-T kinetics would be detected by flow cytometry and droplet digital PCR in peripheral blood and bone marrow at each important time points. Cmax is the peak expansion value of CAR-T cells. AUC(0- day28) refers to the area under curve of CAR-T cell expansion between infusion and day 28 post infusion. They all reflect the pharmacokinetics.	Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28 after the treatment of ESO-T01

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity of ESO-T01	Anti-drug antibody (ADA) would be detected by ELISA.	Baseline, Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Collaborators: Shenzhen Pregene Biopharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: November 9, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T; multiple myeloma; BCMA; In Vivo
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: PRG2402E1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No