Relapsed/Refractory Multiple Myeloma (RRMM)
Conditions
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).
Interventions
BIOLOGICALQLS32015
QLS32015 is a GPRC5D × CD3 bispecific antibody.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Minimum 2 years after infusion | The proportion of subjects achieving stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) after treatment with QLS32015 injection |
| Safety and Tolerability | Minimum 2 years after infusion | The incidence of treatment-emergent adverse events (TEAES) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR) | Minimum 2 years after infusion | Time from first BCMA×CD3 bispecific antibody infusion to first hematologic response，Depth of best hematologic response: The highest-level response achieved at any timepoint |
| Duration of Response (DOR) | Minimum 2 years after infusion | Duration of response (DOR) was defined as the time from first documented hematologic response (≥ partial response \[PR\]) to disease progression or death due to progression, whichever occurred first |
| Overall Survival (OS) | Minimum 2 years after infusion | — |
| Progression-Free Survival (PFS) | Minimum 2 years after infusion | — |
Outcome results
None listed