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

NCT ID: NCT07185477

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-15
• Study Completion Date: 2028-05-31

Brief Summary

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).

Conditions

Relapsed/Refractory Multiple Myeloma (RRMM)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

QLS32015

Group Type: EXPERIMENTAL

QLS32015

Intervention Type: BIOLOGICAL

QLS32015 is a GPRC5D × CD3 bispecific antibody.

Interventions

QLS32015

QLS32015 is a GPRC5D × CD3 bispecific antibody.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

Qilu Pharmaceutical Co., Ltd.

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IIT2025080

Identifier Type: -

Identifier Source: org_study_id