Phase I/II Study of SENL103 for Relapsed or Refractory Multiple Myeloma: A Multicenter, Open-Label, Single-Arm Trial.

Official title

A Multicenter, Open-label, Single-Arm Phase I/II Clinical Study to Evaluate the Safety and Efficacy of SENL103 Autologous T Cell Injection (S103) in Subjects With Relapsed or Refractory Multiple Myeloma.

Overview

To Evaluate Safety and Efficacy of S103 for Treating Relapsed or Refractory Multiple Myeloma

Detailed description

This study is a Phase I/II, single-arm, open-label, single-infusion clinical trial designed to evaluate the clinical efficacy and safety of S103 in patients with Relapsed or Refractory Multiple Myeloma

Interventions

• Biological Autologous BCMA-targeting CAR T cells
  Administration method: intravenous infusion;Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.

Primary outcome measures

• Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) after S103 infusion [Time frame: 28 days]
• Incidence, severity, and relationship of DLTs, AEs and SAEs. [Time frame: 2 years]

Secondary outcome measures (10)

• Pharmacokinetic data parameters.Analysis using CAR DNA copy number measured by qPCR; the highest concentration of S103 cells expanded in peripheral blood after administration [Time frame: 2 years]
• Pharmacodynamics data parameters. Proportion of BCMA-positive cells and Cytokine release. [Time frame: 2 years]
• Objective response rate after S103 infusion [Time frame: 3 months]
• Best overall response after S103 infusion [Time frame: 2 years]
• Duration of Response after S103 infusion [Time frame: 2 years]
• Progression-Free Survival after S103 infusion [Time frame: 2 years]
• Overall survival after S103 infusion [Time frame: 2 years]
• Time to Response after S103 infusion [Time frame: 2 years]
• MRD-negative ORR at Month 3 post-infusion by flow cytometry [Time frame: 3 months]
• MRD-negative ORR at Day-28 post-infusion by flow cytometry. [Time frame: 28 days]

Eligibility criteria

Inclusion criteria

• 1.The subject must understand and voluntarily sign the informed consent form (ICF) before any study-related assessments/procedures.; 2.Male or female subjects aged 18 to 70 years (inclusive) at the time of signing the informed consent form; 3.Life expectancy of no less than 12 weeks; 4.ECOG performance status of 0 to 1; 5.Diagnosis of relapsed/refractory multiple myeloma (RRMM) according to the International Myeloma Working Group (IMWG) diagnostic criteria, with at least 3 prior lines of therapy, including regimens based on proteasome inhibitors, immunomodulatory agents, and CD38 monoclonal antibodies; disease progression documented by radiographic evidence within 12 months following the most recent anti-myeloma therapy.; 6.The subject must have measurable multiple myeloma disease, which must meet at least one of the following criteria:

• Bone marrow cytology, bone marrow biopsy tissue, or flow cytometry showing ≥5% clonal plasma cells or immature plasma cells;
• Serum M-protein levels: IgG type M-protein ≥10 g/L; or IgA, IgD, IgE, IgM type M-protein ≥5 g/L;
• 24-hour urine M-protein level ≥200 mg;
• For light chain multiple myeloma without measurable serum or urine lesions: serum free light chain (sFLC) ≥100 mg/L and abnormal serum κ/λ free light chain ratio;

Exclusion criteria

• 1.Subjects with asymptomatic (smoldering) multiple myeloma; 2.Subjects with multiple myeloma with extramedullary lesions (excluding isolated extramedullary lesions with a maximum cross-sectional diameter ≤3 cm)； 3.Subjects with active plasma cell leukemia (defined as peripheral blood plasma cells >5%), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloidosis at screening; 4.Subjects with clinically significant cardiovascular disease, including any of the following:

• QTc interval >470 ms (QTc interval corrected using the Fridericia formula);
• New York Heart Association (NYHA) Class II or higher heart failure;
• Unstable angina or acute myocardial infarction within 6 months prior to signing the informed consent form (ICF);
• Left ventricular ejection fraction (LVEF) <50%;
• Poorly controlled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg); Arrhythmia that is either clinically significant or requires antiarrhythmic therapy (e.g., persistent ventricular tachycardia, ventricular fibrillation, torsades de pointes, or complete left bundle branch block); 5.Subjects who have previously received BCMA-targeted therapies, BCMA CAR-T therapy, or other cellular therapies 6.Subjects who have previously received the following antineoplastic therapies: monoclonal antibody treatment for multiple myeloma within 21 days prior to autologous stem cell collection, cytotoxic chemotherapy or proteasome inhibitors within 14 days prior to autologous stem cell collection, immunomodulatory agents within 7 days prior to autologous stem cell collection, or any other antineoplastic therapies within 14 days or at least 5 half-lives (whichever is longer) prior to autologous stem cell collection; 7.Subjects with interstitial lung disease or interstitial pneumonia at the time of signing the ICF; 8.Subjects with active autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and psoriasis) or other conditions requiring immunosuppressive therapy (except for low-dose corticosteroids) at screening; 9.Subjects who have received live or inactivated vaccines within 28 days prior to signing the ICF;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07421856 · S103-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗