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

Korábbi kezelés

• Prior GPRC5D-targeted immunotherapy.
• Grade \>2 peripheral neuropathy or ≥grade 2 painful neuropathy at screening (regardless of current medication).
• Initiation of bridging therapy for BCMA CAR-T cell treatment.
• 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.
• Contraindications to required concomitant medications/supportive care.

Más betegség

• Investigator-assessed contraindications to GPRC5D×CD3 bispecific antibody therapy (e.g., severe cardiopulmonary diseases incompatible with treatment).
• Known intolerance, hypersensitivity, or contraindication to GPRC5D×CD3 bispecific antibody components.
• 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.
• Active gastrointestinal disorders affecting swallowing or drug absorption.
• Active psychiatric/medical conditions impairing compliance/consent capacity per investigator judgment.
• Any condition interfering with study procedures.

Laborértékek

• 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.

Egyéb

• Pregnancy or lactation.
• Inability/unwillingness to comply with protocol.

• 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.