Multiple myeloma (MM)
Conditions
Interventions
Dose group 1:SKIC-03 injection, 2 mg/dose, intravenous infusion on D0, D3, D6, D9 in cycle 1.
Dose group 2:SKIC-03 injection, 4 mg/dose, intravenous infusion on D0, D3, D6, D9 in cycle 1.
Dose group 3:SKIC-03 injection, 6 mg/dose, intravenous infusion on D0, D4, D8, D12 in cycle 1
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18-75 years, any gender; 2. Expected survival time over 12 weeks; 3. Patients with relapsed/refractory multiple myeloma must meet the following disease-related inclusion criteria: Diagnosed with multiple myeloma (MM) according to the International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma. Have received at least 2 types of anti-multiple myeloma treatments (including at least one proteasome inhibitor and one immunomodulatory drug); Have measurable multiple myeloma lesions, including any of the following: Serum M protein = 0.5 g/dL (5 g/L); Urine M protein = 200 mg/24 h; Serum free light chain (sFLC) test: abnormal FLC ratio (?/?) and involved FLC = 100 mg/L; Or clinical relapse, defined as the appearance of new bone lesions or soft tissue plasmacytomas (excluding osteoporotic fractures); existing plasmacytomas or bone lesions confirmed to enlarge (sum of the product of the diameters [SPD] of measurable lesions increased =50%, with an absolute increase =1 cm). 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 5. Prior to screening (baseline), the following conditions must be met: blood routine tests (no transfusions, platelet transfusions, or growth factor support within 7 days before testing): absolute neutrophil count = 0.6 × 10^9/L, platelets = 50 × 10^9/L, hemoglobin = 60 g/L, lymphocyte count = 0.5 × 10^9/L; blood biochemistry: creatinine clearance = 40 ml/min, serum ALT/AST = 2.5 times the upper limit of normal, total bilirubin = 1.5 times the upper limit of normal; 6. Male and female patients of childbearing potential must use reliable contraception before entering the trial and throughout the study until 30 days after drug discontinuation; the reliability of contraception will be determined by the principal investigator or designated personnel; 7. Able to understand this trial and have signed the informed consent form. 8. Completion of peripheral blood T lymphocyte subset analysis (CD3, CD4, CD8, CD4/CD8 ratio) during the screening period.
Exclusion criteria
Exclusion criteria: 1. Other uncontrolled malignant tumors; 2. Prior CAR-T or other genetically modified T-cell therapy within 6 months; 3. Prior BCMA- or GPRC5D-targeted bispecific antibody therapy within 6 months; 4. Any anti-myeloma therapy within 14 days prior to first dose; 5. HIV positive, active hepatitis B or C infection; 6. History of CNS lymphoma, malignant CSF cells, or brain metastases; 7. Uncontrolled active infection within 14 days prior to enrollment; 8. Requiring urgent treatment due to tumor mass effect (e.g., bowel obstruction, vascular compression); 9. Severe cardiovascular or cerebrovascular diseases; 10. Unstable thromboembolic events within 30 days prior to enrollment; 11. Long-term immunosuppressive therapy for autoimmune disease or organ transplantation; 12. Pregnant or lactating women, or planned pregnancy within 18 months after treatment; 13. Other conditions deemed unsuitable by the investigator.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR); Stringent Complete Response (sCR) rate;Complete Response (CR) rate;Very Good Partial Response (VGPR) rate;Partial Response (PR) rate;Duration of Response (DoR);Progression-Free Survival (PFS);Overall Survival (OS);Minimal Residual Disease (MRD) negativity rate;Pharmacokinetic parameter - Peak concentration (Cmax);Pharmacokinetic parameter - Time to peak concentration (Tmax);Pharmacokinetic parameter - Half-life (t1/2);Pharmacokinetic parameter - Area under the curve (AUC);Changes in clonal myeloma cells in peripheral blood;Changes in clonal myeloma cells in bone marrow;Expression level and kinetics of CAR molecules on T cell surface;Incidence and titers of anti-drug antibodies (ADA);Incidence and titers of neutralizing antibodies (Nab).; | — |
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity (DLT) and its incidence rate;Maximum tolerated dose (MTD);Recommended Phase II dose (RP2D);Frequency and severity grading of Adverse Events (AEs);Frequency and severity grading of Serious Adverse Events (SAEs).; | — |
Countries
China
Contacts
Public ContactTing Niu
West China Hospital, Sichuan University
Outcome results
None listed