Eque-cel for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

Официальное название

A Phase I/II Clinical Study of Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (Equecabtagene Autoleucel) for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

Обзор

This study is a single-armed, open-label, multicenter Phase 1/2 study to evaluate the efficacy and safety of Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (Equecabtagene Autoleucel) in subjects with relapsed and refractory Multiple Myeloma.

Подробное описание

This study is divided into two stages: Part 1 and Part 2. Part 1: For exploratory research purposes, no more than 3 subjects will be enrolled at an exploratory dose.

Part 2: The purpose of this phase is to explore the efficacy of Equecabtagene Autoleucel (Eque-cel) as a last-line treatment for RRMM and further confirm its safety.

In this Study，Leukapheresis procedure will be performed to manufacture Eque-cel modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide is performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of Eque-cel at 1.0 x 10\^6 CAR+ T cells/Kg or 0.5 x 10\^6 CAR+ T cells/Kg（if all three subjects in Part 1 experience the Toxicity Requiring Dose Reduction）. Subjects will be followed in the study for a minimum of 2 years after Eque-cel infusion.

Вмешательства

• Препарат Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (Eque-cel)
  Eque-cel consists of autologous T lymphocytes transduced with anti-BCMA CAR lentiviral vector that contains a unique CAR structure with a fully human single-chain variable fragment (scFv).

Первичные конечные точки

• Safety endpoint (Part 1)- Adverse Event（AEs） [Срок оценки: up to 2 years from Eque-cel infusion]
• Safety endpoint (Part 1)-CRS [Срок оценки: up to 2 years from Eque-cel infusion]
• Safety endpoint (Part 1)-ICANS [Срок оценки: up to 2 years from Eque-cel infusion]
• Efficacy endpoint (Part 2): Independent Review Committee (IRC)-assessed ORR [Срок оценки: up to 2 years from Eque-cel infusion]

Вторичные конечные точки (12)

• Safety endpoint (Part 2)- Adverse Event（AEs） [Срок оценки: up to 2 years from Eque-cel infusion]
• Efficacy endpoint -Investigator-assessed overall response rate (ORR) [Срок оценки: up to 2 years from Eque-cel infusion]
• Efficacy endpoint -IRC- and investigator-assessed ORR [Срок оценки: up to 2 years from Eque-cel infusion]
• Efficacy endpoint -IRC and investigator-assessed duration of response (DOR) [Срок оценки: up to 2 years from Eque-cel infusion]
• IRC and investigator-assessed time to response (TTR) [Срок оценки: up to 2 years from Eque-cel infusion]
• IRC and investigator-assessed time to complete response (TTCR) [Срок оценки: up to 2 years from Eque-cel infusion]
• Minimal residual disease (MRD) assessment by flow cytometry [Срок оценки: up to 2 years from Eque-cel infusion]
• IRC and investigator-assessed progression-free survival (PFS) [Срок оценки: up to 2 years from Eque-cel infusion]
• Overall survival (OS) [Срок оценки: up to 2 years from Eque-cel infusion]
• Pharmacokinetic Endpoint-Cmax [Срок оценки: up to 2 years from Eque-cel infusion]
• Pharmacokinetic Endpoint-Tmax [Срок оценки: up to 2 years from Eque-cel infusion]
• Pharmacokinetic Endpoint-AUC [Срок оценки: up to 2 years from Eque-cel infusion]

Критерии участия

• Inclusion Criteria
• 1\. Aged 18 to 70 years, male or female.
• 2\. Patients with a confirmed diagnosis of relapsed/refractory multiple myeloma according to the IMWG diagnostic criteria.
• 3\. Patients who have received at least three prior treatment regimens (including proteasome inhibitors, immunomodulatory agents, and anti-CD38 antibody-based chemotherapy regimens) and have documented disease progression during or within 12 months of their most recent anti-myeloma treatment.
• 4\. Patients with measurable disease at screening, as determined by any of the following criteria:
• Serum M-protein level: IgG type M-protein level ≥ 10 g/L, IgA, IgD, IgE, IgM type M-protein level ≥ 5 g/L
• Urinary M-protein level ≥ 200 mg/24 hours
• 5\. Light-chain multiple myeloma without measurable M protein in serum or urine: involved serum free light chain ≥ 100 mg/L with an abnormal serum κ/λ free light chain ratio. ECOG PS 0 or 1.
• 6\. Patients must have adequate organ function and meet all of the following pre-enrollment laboratory test results:

Hematological Tests:

• Absolute Neutrophil Count (ANC) ≥ 1×109/L (Supportive growth factors are permitted, but supportive treatment must not have been administered within 7 days prior to the laboratory test)
• Absolute Lymphocyte Count (ALC) ≥ 0.3×109/L
• Platelet Count ≥ 50×109/L (Supportive transfusions must not have been administered within 7 days prior to the laboratory test)
• Hemoglobin ≥ 60 g/L (Red blood cell \[RBC\] transfusions must not have been administered within 7 days prior to the laboratory test, but recombinant human erythropoietin is permitted)

Liver Function:

• ALT and AST ≤ 2.5×upper limit of normal (ULN)
• Serum Total Bilirubin ≤ 1.5 x ULN Renal Function: Creatinine clearance (CrCl) calculated using the Cockcroft-Gault formula ≥ 40 mL/min CrCl = (140 - age) × weight (kg) × \[0.85 for women\] / 72 × \[ serum creatinine (mg/dL)\]

Coagulation function:

• Fibrinogen ≥ 1.0 g/L
• Activated partial thromboplastin time (APTT) ≤ 1.5× ULN
• Prothrombin time (PT) ≤ 1.5× ULN Corrected serum calcium ≤11 mg/dL Oxygen saturation > 91% Left ventricular ejection fraction (LVEF) ≥ 50%.
• 7\. Female patients of childbearing potential or male patients with partners of childbearing potential agree to use effective contraception (safe-day contraception not included) throughout the study period from screening through one year after Eque-cel infusion.

"Effective contraceptive methods" specifically refers to: User-independent methods: 1) Intrauterine devices, intrauterine hormone-releasing systems; 2) Partner has undergone vasectomy.

User-dependent methods: 1) Combined hormonal contraception (containing estrogen and progestin) with ovulation suppression:

Oral; 2) Progestin-only hormonal contraception with ovulation suppression ( oral).

-8. Prior to screening, subjects must manually sign an Institutional Review Board-approved ICF.

Критерии исключения

• 1\. Patients with graft-versus-host disease (GVHD) or requiring long-term use of immunosuppressants.
• 2\. Patients with a history of BCMA-targeted therapy.
• 3\. Patients who have undergone autologous hematopoietic stem cell transplantation (auto-HSCT) within 12 weeks prior to apheresis, two auto-HSCTs, or prior allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• 4\. Patients who have received prior anti-myeloma therapy, including:
• Monoclonal antibody therapy within 21 days prior to apheresis.
• Cytotoxic chemotherapy or proteasome inhibitor therapy within 14 days prior to apheresis.
• Immunomodulatory therapy within 7 days prior to apheresis.
• Other anti-myeloma therapy within 14 days or within 5 half-lives (whichever is longer) prior to apheresis.
• 5\. Use of systemic corticosteroids at a therapeutic dose (defined as >20 mg/day of prednisone or equivalent) within 7 days prior to apheresis.

Physiological replacement steroids, topical steroids, and inhaled steroids are permitted.

• 6\. Patients with uncontrolled hypertension despite medical therapy.
• 7\. Severe cardiac disease, including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association \[NYHA\] grade ≥ III), and severe arrhythmia.
• 8\. Unstable systemic disease as determined by the investigator, including but not limited to severe liver, renal, or metabolic disease requiring treatment.
• 9\. Patients with malignancies other than multiple myeloma (MM) within 5 years prior to screening.

excluding adequately treated cervical epithelial cell adenocarcinoma, basal cell carcinoma or squamous cell skin cancer, localized prostate cancer after curative surgery, and ductal carcinoma in situ after curative surgery.

• 10\. Patients with a history of solid organ transplantation.
• 11\. Patients with suspected or confirmed central nervous system infiltration by plasma cell neoplasms.
• 12\. Multiple myeloma patients with extramedullary lesions (excluding those with only paraskeletal extramedullary lesions where the single largest transverse diameter is ≤3cm).
• 13\. Multiple myeloma patients with concomitant plasma cell leukemia (peripheral blood plasma cell count ≥5%).
• 14\. Major surgery within 2 weeks prior to apheresis or planned surgery within 2 weeks after study treatment (subjects scheduled for local anesthesia surgery may participate in this study).
• 15\. Received investigational drugs from other interventional clinical trials within 1 month prior to signing the Informed Consent Form (ICF).
• 16\. Patients with an uncontrolled active infection (excluding CTCAE Grade 2 urinary tract infection or respiratory infection) within 7 days prior to apheresis.
• 17\. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with detectable hepatitis B virus (HBV) DNA in peripheral blood; Hepatitis C virus (HCV) positive with hepatitis C virus (HCV) RNA positive in peripheral blood; Human Immunodeficiency Virus (HIV) antibody positive; Cytomegalovirus (CMV) DNA test positive; Syphilis test positive.
• 18\. Pregnant or lactating women.
• 19\. Patients with psychiatric disorders, impaired consciousness, or central nervous system disease.
• 20\. Patients whose non-hematologic toxicities from previous antimyeloma therapy have not resolved to baseline or Grade ≤ 1 (NCI-CTCAE v5.0) (excluding alopecia and Grade 2 peripheral neuropathy).
• 21\. Other conditions deemed ineligible for enrollment by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Япония · 3 центра

• Institute of Science Tokyo Hospital — Bunkyo-ku
• Nihon University Itabashi Hospital — Itabashi-ku
• Japanese Red Cross Medical Center — Shibuya-ku

Идентификаторы

NCT: NCT07510100 · CT103AJ001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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