BCMA/CD3 Bispecific Antibody Treatment for Newly Diagnosed Amyloidosis

Official title

A Single-arm Single-center Trial of BCMA/CD3 Bispecific Antibody Treatment for Newly Diagnosed Amyloidosis (AL-003)

Overview

This is a prospective, single-arm, single-center clinical study designed to evaluate the efficacy and safety of low-dose BCMA/CD3 bispecific antibody (CM336) in patients newly diagnosed with systemic light chain (AL) amyloidosis.

Interventions

• Drug anti-BCMA/CD3 bispecific antibody
  CM336 is a bispecific T-cell engager targeting B-cell maturation antigen (BCMA) and CD3. In this study, CM336 is administered subcutaneously with a step-up dosing strategy in Cycle 1 (3 mg Day 1, 20 mg Day 4, 40 mg Day 8 and onwards weekly). Patients who achieve ≥VGPR by Cycle 4 may switch to 80 mg every two weeks from Cycle 5. The total treatment duration is up to 12 cycles (28 days per cycle), with follow-up for safety and efficacy endpoints including hematologic and organ response.

Primary outcome measures

• Rate of Hematologic Very Good Partial Response (VGPR) or Better [Time frame: 4 months]
• Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From the first dose through 30 days after the last dose, up to approximately 24 months.]

Secondary outcome measures (8)

• Time to First Hematologic Response (TTR) [Time frame: From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months.]
• Best Hematologic Response Achieved [Time frame: From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months.]
• Duration of Hematologic Response (DOR) [Time frame: From the date of first documented hematologic response to the date of disease progression or death, whichever occurs first, up to approximately 24 months.]
• Overall Response Rate (ORR) [Time frame: The overall response rate (ORR) was evaluated at the end of cycle 4, 6, and 12 (28 days per cycle).]
• Progression-Free Survival (PFS) [Time frame: From the first dose to progression from any cause, up to approximately 36 months.]
• Overall Survival (OS) [Time frame: From the first dose to death from any cause, up to approximately 36 months.]
• Minimal Residual Disease (MRD) Negativity Rate [Time frame: From baseline to 24 months, assessed at predefined response evaluation time points.]
• Organ Response [Time frame: 12 months]

Eligibility criteria

• The patient is informed of and voluntarily signs the informed consent form (ICF).
• Age ≥18 years, regardless of sex.
• Confirmed diagnosis of primary light-chain (AL) amyloidosis, in accordance with the Guidelines for the Diagnosis and Treatment of Systemic Light-chain Amyloidosis (2021 Revision).
• Measurable disease at screening, defined as:

• Difference between involved and uninvolved free light chains (dFLC) ≥50 mg/L, or
• Serum involved free light chain ≥50 mg/L with an abnormal κ:λ ratio.
• ECOG performance status ≤2.
• Adequate organ function within 3 days prior to the first dose of the investigational drug, meeting all of the following criteria:

i. Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L, with no granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) administration within 7 days, and no pegylated G-CSF administration within 14 days prior to testing; ii. Hemoglobin (Hb) ≥75 g/L, with no whole blood or red blood cell transfusion within 7 days prior to testing; iii. Platelet count ≥70 × 10⁹/L, with no whole blood transfusion, platelet transfusion, or thrombopoietin receptor agonist treatment within 7 days prior to testing; iv. Hepatic function: alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤3 × ULN, total bilirubin ≤2 × ULN (subjects with Gilbert's syndrome are eligible if direct bilirubin ≤2 × ULN); v. Coagulation: international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5 × ULN; vi. Renal function: estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m², calculated using the CKD-EPI equation.

• Male and female patients of childbearing potential, and their partners, must agree to use effective contraceptive methods deemed appropriate by the investigator throughout the treatment period and for at least 3 months thereafter.
• Male patients must agree not to donate sperm from the screening period until 90 days after the last dose of the investigational drug.
• The patient must be willing and able to comply with all study procedures and follow-up visits.
• Women not of childbearing potential are eligible for enrollment. Women of childbearing potential must have a negative serum or urine β-hCG pregnancy test at screening.

Note:

A woman of childbearing potential is defined as a sexually mature woman who has not undergone surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) and has not been postmenopausal for at least 12 consecutive months for reasons other than medical treatment. Women using oral contraceptives or intrauterine devices are considered of childbearing potential. Male subjects (including those who have undergone vasectomy) must agree to use condoms during sexual intercourse with women of childbearing potential and must have no plans to father a child from the time of signing the ICF until 3 months after the last dose of study treatment.

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

China · 1 center

• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin

Identifiers

NCT: NCT07151690 · IIT2025066

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗