IASO104 for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

Institute of Hematology & Blood Diseases Hospital, China

Status and phase

Begins enrollment this month

Early Phase 1

Conditions

Relapsed/Refractory Multiple Myeloma (RRMM)

Plasma Cell Leukemia (PCL)

Treatments

Biological: IASO104

Study type

Interventional

Funder types

Other

Identifiers

NCT07185490

IIT2025081

Nanjing Reindeer Biotechnology (Other Grant/Funding Number)

Details and patient eligibility

About

This study is a single-center, open-label, dose-exploration trial designed to evaluate the tolerability and safety of different doses of IASO104 in patients with relapsed/refractory plasma cell neoplasms, determine the recommended dose of IASO104, and assess its pharmacokinetic and pharmacodynamic characteristics. Additionally, the study will preliminarily observe the efficacy of the investigational drug in a small sample of subjects with relapsed/refractory multiple myeloma.

Full description

This study adopts a "3+3" dose-escalation design, with three predefined dose levels: 0.5×10⁶ CAR-T cells/kg, 1.0×10⁶ CAR-T cells/kg, and 3.0×10⁶ CAR-T cells/kg, administered as a single infusion.For each dose group, the first subject must be observed for at least 2 weeks after infusion before subsequent subjects can be treated. If stable biological activity or clinical benefit is observed at a lower dose level, the study may proceed with 1-2 expanded dose groups at lower levels after discussion between the investigator and sponsor, without requiring MTD determination.During the dose-escalation phase, 2-3 subjects will be enrolled per dose level, with the total number of subjects depending on the escalation progression (estimated 4-6 subjects in this phase). Treatment in the next dose group may only begin after all subjects in the current group have completed DLT assessment post-infusion.

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18-75 years, any gender.
Diagnosis of multiple myeloma (MM) per International Myeloma Working Group (IMWG) diagnostic criteria.
Prior therapy requirements:

MM patients: ≥3 prior lines of therapy, including:
- 1 proteasome inhibitor (PI)
- 1 immunomodulatory drug (IMiD)
- 1 anti-CD38 monoclonal antibody Exception: No minimum line requirement for subjects refractory to PIs, IMiDs, and anti-CD38 therapy.
Primary plasma cell leukemia (pPCL): ≥1 prior line including ≥1 PI and ≥1 IMiD.
Documented disease progression during/within 12 months after last anti-myeloma therapy (exemption: No 12-month requirement if last line was CAR-T).
Measurable disease at screening (≥1 of the following):

Serum M-protein:

IgG ≥10 g/L IgA/IgD/IgE/IgM ≥5 g/L Urine M-protein ≥200 mg/24h Serum free light chains (FLC): Involved FLC ≥100 mg/L with abnormal κ/λ ratio Bone marrow plasma cells ≥30% (if no measurable M-protein/FLC).
ECOG performance status 0-1.
Life expectancy ≥12 weeks.
Adequate organ function (all lab values within 7 days prior to enrollment):

Hematology:

Absolute neutrophil count (ANC) ≥1×10⁹/L (allowed: growth factor support, but none within 7 days) Absolute lymphocyte count (ALC) ≥0.3×10⁹/L Platelets ≥50×10⁹/L (no transfusion within 7 days) Hemoglobin ≥60 g/L (no RBC transfusion within 7 days; erythropoietin allowed)

Liver:

ALT/AST ≤2.5×ULN Total bilirubin ≤1.5×ULN Renal: Calculated CrCl ≥40 mL/min (Cockcroft-Gault)

Coagulation:

Fibrinogen ≥1.0 g/L aPTT/PT ≤1.5×ULN Pulmonary: SpO₂ >91% (room air) Cardiac: LVEF ≥50% (echocardiography).
Contraception: Subjects/partners must use effective contraception from consent through 1 year post CAR-T infusion (excluded: calendar method).
Signed informed consent approved by the Ethics Committee prior to screening.

Exclusion criteria

Active graft-versus-host disease (GVHD) or requiring long-term immunosuppressive therapy.
Prior hematopoietic stem cell transplantation (HSCT):

Autologous HSCT (Auto-HSCT) within 12 weeks before apheresis,

≥2 prior Auto-HSCTs, Any prior allogeneic HSCT (Allo-HSCT).
Prior cell therapy targeting plasma cells within 3 months before apheresis, or detectable residual cellular therapy products in peripheral blood.
Recent anti-myeloma therapies (relative to apheresis):

Monoclonal antibody treatment within 21 days, Cytotoxic chemotherapy or proteasome inhibitors within 14 days, Immunomodulatory drugs within 7 days, Other anti-tumor therapies within 14 days or 5 half-lives (whichever is shorter).
Chronic corticosteroid use (>20 mg/day prednisone or equivalent), except for physiologic replacement, topical, or inhaled use.
Uncontrolled hypertension despite medication.
Severe cardiac disease, including:

Unstable angina, Myocardial infarction (within 6 months before screening), Congestive heart failure (NYHA Class ≥III), Severe arrhythmias.
Unstable systemic illnesses per investigator's judgment (e.g., severe hepatic, renal, or metabolic disorders requiring medication).
Other malignancies within 5 years, excluding:

Carcinoma in situ of the cervix, Basal/squamous cell skin cancer, Localized prostate cancer post-radical resection, Ductal breast carcinoma in situ post-resection.
History of solid organ transplantation.
Suspected or confirmed CNS involvement by plasma cell neoplasms.
Major surgery within 2 weeks before apheresis or planned within 2 weeks post-treatment (allowed: minor procedures under local anesthesia).
Investigational drugs within 1 month before apheresis.
Uncontrolled active infections:

Persistent symptoms despite appropriate therapy, Requiring IV antimicrobials at screening.
Viral infections:

HBV: HBsAg(+) or HBcAb(+) with detectable HBV DNA, HCV: HCV Ab(+) with detectable HCV RNA, HIV Ab(+), CMV DNA(+), Syphilis: TRUST(+) and TPPA(+).
Pregnancy or lactation.
Psychiatric disorders, cognitive impairment, or active CNS diseases.
Other conditions deemed ineligible by the investigator.