A Single-arm Single-center Trial of Bridging GPRC5D/CD3 Bispecific Antibody Treatment With BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma (QLS32015)

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Relapsed/Refractory Multiple Myeloma (RRMM)

Treatments: Biological: QLS32015

Study type: Interventional

Funder types: Other

Identifiers

NCT07185477

IIT2025080

Qilu Pharmaceutical Co., Ltd. (Other Grant/Funding Number)

Details and patient eligibility

About

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).

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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), plus Peripheral 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, 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.

Exclusion criteria

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:

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

QLS32015

Experimental group

Treatment:

Biological: QLS32015