Low-dose BCMA/CD3 (CM336) treatment for newly diagnosed AL (light-chain) amyloidosis

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

This trial will try a low-dose BCMA/CD3 bispecific antibody (CM336) in adults newly diagnosed with systemic light-chain (AL) amyloidosis to see if it is safe and lowers abnormal light-chain levels and helps organ function.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Locations: 1 site (Tianjin)
• Trial ID: NCT07151690 on ClinicalTrials.gov

What this trial studies

This prospective, single-arm, single-center phase 2 trial tests low-dose CM336, a BCMA/CD3 bispecific antibody, in adults with newly diagnosed systemic light‑chain (AL) amyloidosis and measurable disease. Participants receive the investigational antibody and are followed for safety, changes in involved free light chains (dFLC), and organ function over the treatment and follow-up periods. Key inclusion requirements include age ≥18, ECOG performance status ≤2, measurable dFLC (≥50 mg/L), and adequate blood counts and organ function. The trial aims to document preliminary hematologic and organ responses and to characterize adverse events to guide further development.

Who should consider this trial

Good fit: Adults (≥18) newly diagnosed with systemic AL amyloidosis who have measurable disease (dFLC ≥50 mg/L), ECOG ≤2, and adequate organ and blood function are the intended participants.

Not a fit: Patients with non‑AL forms of amyloidosis, very advanced organ failure, inadequate blood counts, or those who have already received anti‑plasma cell therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, CM336 could offer a targeted treatment that more rapidly lowers the toxic light chains and may improve organ outcomes for patients with newly diagnosed AL amyloidosis.

How similar studies have performed: BCMA‑targeted therapies such as CAR‑T cells and bispecific antibodies have shown strong activity in multiple myeloma, but use of BCMA/CD3 bispecifics specifically in newly diagnosed AL amyloidosis is relatively novel with limited prior data.

Eligibility criteria

1. The patient is informed of and voluntarily signs the informed consent form (ICF).
2. Age ≥18 years, regardless of sex.
3. 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).
4. 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.
5. ECOG performance status ≤2.
6. 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.
7. 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.
8. Male patients must agree not to donate sperm from the screening period until 90 days after the last dose of the investigational drug.
9. The patient must be willing and able to comply with all study procedures and follow-up visits.
10. 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.

Where this trial is running

Tianjin

• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin, China (Recruiting)

Study contacts

• Study coordinator: Gang An, MD

Conditions Systemic Light Chain Amyloidosis; BCMA/CD3 bispecific antibody; CM336