CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.

主要终点：Overall Response Rate (ORR) · 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 · Minimum 2 years after infusion；Safety and Tolerability · The incidence of treatment-emergent adverse events (TEAES) · Minimum 2 years after infusion
次要终点：Time to Response (TTR)；Duration of Response (DOR)；Overall Survival (OS)；Progression-Free Survival (PFS)

• QLS32015 · EXPERIMENTAL

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).