BCMA/CD3 Bispecific Antibody as Bridging Therapy Before CAR-T Cell Infusion in RRMM

Официальное название

A Prospective Single-Arm, Single-Center Study of BCMA/CD3 Bispecific Antibody as Bridging Therapy Before CAR-T Cell Infusion in Relapsed or Refractory Multiple Myeloma

Обзор

This study is a prospective, single-arm, multicenter trial designed to evaluate the hematologic response rate and safety of BCMA/CD3 bispecific antibody bridging therapy prior to CAR-T cell infusion in patients with relapsed/refractory multiple myeloma (RRMM).

Вмешательства

• Биопрепарат CM336 (BCMA/CD3 bispecific antibody)
  CM336 is a BCMA × CD3 bispecific antibody.

Первичные конечные точки

• Overall Response Rate (ORR) [Срок оценки: Minimum 2 years after infusion]
• Safety and Tolerability [Срок оценки: Minimum 2 years after infusion]

Вторичные конечные точки (4)

• Time to Response (TTR) [Срок оценки: Minimum 2 years after infusion.]
• Duration of Response (DOR) [Срок оценки: Minimum 2 years after infusion]
• Overall Survival (OS) [Срок оценки: Minimum 2 years after infusion]
• Progression-Free Survival (PFS) [Срок оценки: Minimum 2 years after infusion]

Критерии участия

Критерии включения

• 1.Voluntary Participation: Ability to understand and voluntarily sign the informed consent form (ICF).2.Age ≥18 years.3.Confirmed symptomatic MM diagnosis per the Chinese Guidelines for Diagnosis and Management of Multiple Myeloma (2022 Revision).4.Relapsed/Refractory MM (RRMM) meeting one of the following:Triple-class refractory RRMM: Resistant to ≥1 immunomodulatory drug (IMiD), ≥1 proteasome inhibitor (PI), and ≥1 anti-CD38 monoclonal antibody.Penta-drug refractory RRMM: Resistant to ≥2 IMiDs, ≥2 PIs, and ≥1 anti-CD38 antibody.Secondary plasma cell leukemia (sPCL):MM diagnosis per Chinese Guidelines (2022), plusPeripheral blood plasma cells ≥20% of leukocytes or absolute circulating plasma cells >2×10⁹/L.5.Successful apheresis for CAR-T cell manufacturing.6.ECOG performance status ≤3.7.No active infections:HBV-DNA negative, HCV-RNA negative, HIV negative.8.Liver function:Total bilirubin <1.5×ULN (<3×ULN for Gilbert's syndrome).AST/ALT <3×ULN.9.Renal function: Calculated CrCl ≥30 mL/min (Cockcroft-Gault formula).10.Baseline oxygen saturation >92% (room air).11.Hematologic criteria (within 7 days of screening):WBC ≥1.0×10⁹/L, ANC ≥1.0×10⁹/L, hemoglobin ≥70 g/L, andPlatelets ≥75×10⁹/L (or ≥50×10⁹/L if bone marrow plasma cells ≥50%).Investigator discretion permitted for clinical justification.12.Growth factor restrictions:2-week washout required for erythropoietin, G-CSF, GM-CSF, or thrombopoietin agonists (e.g., eltrombopag).13.Reproductive requirements:Non-childbearing women eligible;Childbearing potential women: Negative serum/urine pregnancy test (β-hCG) at screening.14.Contraception:Males/females of reproductive potential must use effective contraception (per investigator judgment) during treatment and for ≥3 months post CAR-T infusion.15.Sperm donation prohibition: Males must refrain from sperm donation from screening until 90 days post-treatment.16.Compliance: Willing and able to complete study procedures and follow-up.

Критерии исключения

• 1.Prior GPRC5D-targeted immunotherapy.2.Investigator-assessed contraindications to GPRC5D×CD3 bispecific antibody therapy (e.g., severe cardiopulmonary diseases incompatible with treatment).3.Grade >2 peripheral neuropathy or ≥grade 2 painful neuropathy at screening (regardless of current medication).4.Known intolerance, hypersensitivity, or contraindication to GPRC5D×CD3 bispecific antibody components.5.Initiation of bridging therapy for BCMA CAR-T cell treatment.6.Unstable/active cardiovascular or cerebrovascular disease, including any of:a. Unstable angina, symptomatic myocardial ischemia, myocardial infarction, or coronary revascularization within 180 days prior to first dose.b. Uncontrolled hypertension (>140/90 mmHg with historical readings >180/100 mmHg within 6 months).c. Clinically significant uncontrolled arrhythmias (excluded: asymptomatic 1st-degree AV block or LAFB/RBBB).d. LVEF <40% by echocardiography.e. Stroke or intracranial hemorrhage within 12 months before screening.f. Pre-treatment severe thrombotic events.7.Active HIV infection or seropositivity.8.Active HBV/HCV infection:HBV: HBsAg(+) requires confirmed negative HBV-DNA PCR (allowed: if on antiviral therapy with confirmed suppression).HCV: HCV Ab(+) requires negative HCV-RNA PCR.9.Pregnancy or lactation.10.Active gastrointestinal disorders affecting swallowing or drug absorption.11.Major surgery within 2 weeks pre-enrollment or planned during study (excluded: kyphoplasty/vertebroplasty; allowed: local anesthesia procedures).12.Live vaccines within 4 weeks before first study dose.13.Active psychiatric/medical conditions impairing compliance/consent capacity per investigator judgment.14.Contraindications to required concomitant medications/supportive care.15.Any condition interfering with study procedures.16.Inability/unwillingness to comply with protocol.

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07407010 · IIT2024047

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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