A Single-arm Single-center Trial of Bridging GPRC5D/CD3 Bispecific Antibody Treatment With BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma

Обзор

This study is a prospective, single-arm, multicenter trial designed to evaluate the hematologic response rate and safety of GPRC5D/CD3 bispecific antibody bridging therapy prior to CAR-T cell infusion in patients with relapsed/refractory multiple myeloma (RRMM).

Вмешательства

• Биопрепарат QLS32015
  QLS32015 is a GPRC5D × 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

• Voluntary Participation: Ability to understand and voluntarily sign the informed consent form (ICF).
• Age ≥18 years.
• Confirmed symptomatic MM diagnosis per the Chinese Guidelines for Diagnosis and Management of Multiple Myeloma (2022 Revision).
• 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), plus Peripheral blood plasma cells ≥20% of leukocytes or absolute circulating plasma cells >2×10⁹/L.

• Successful apheresis for CAR-T cell manufacturing.
• ECOG performance status ≤3.
• No active infections:

HBV-DNA negative, HCV-RNA negative, HIV negative.

• Liver function:

Total bilirubin <1.5×ULN (<3×ULN for Gilbert's syndrome). AST/ALT <3×ULN.

• Renal function: Calculated CrCl ≥30 mL/min (Cockcroft-Gault formula).
• Baseline oxygen saturation >92% (room air).
• Hematologic criteria (within 7 days of screening):

WBC ≥1.0×10⁹/L, ANC ≥1.0×10⁹/L, hemoglobin ≥70 g/L, and Platelets ≥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

• Prior GPRC5D-targeted immunotherapy.
• Investigator-assessed contraindications to GPRC5D×CD3 bispecific antibody therapy (e.g., severe cardiopulmonary diseases incompatible with treatment).
• Grade >2 peripheral neuropathy or ≥grade 2 painful neuropathy at screening (regardless of current medication).
• Known intolerance, hypersensitivity, or contraindication to GPRC5D×CD3 bispecific antibody components.
• Initiation of bridging therapy for BCMA CAR-T cell treatment.
• Unstable/active cardiovascular or cerebrovascular disease, including any of:

• Unstable angina, symptomatic myocardial ischemia, myocardial infarction, or coronary revascularization within 180 days prior to first dose.
• Uncontrolled hypertension (>140/90 mmHg with historical readings >180/100 mmHg within 6 months).
• Clinically significant uncontrolled arrhythmias (excluded: asymptomatic 1st-degree AV block or LAFB/RBBB).
• LVEF <40% by echocardiography.
• Stroke or intracranial hemorrhage within 12 months before screening.
• Pre-treatment severe thrombotic events.
• Active HIV infection or seropositivity.
• 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.

• Pregnancy or lactation.
• Active gastrointestinal disorders affecting swallowing or drug absorption.
• Major surgery within 2 weeks pre-enrollment or planned during study (excluded: kyphoplasty/vertebroplasty; allowed: local anesthesia procedures).
• Live vaccines within 4 weeks before first study dose.
• Active psychiatric/medical conditions impairing compliance/consent capacity per investigator judgment.
• Contraindications to required concomitant medications/supportive care.
• Any condition interfering with study procedures.
• 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: NCT07185477 · IIT2025080 · Qilu Pharmaceutical Co., Ltd.

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗