BCMA/CD3 Bispecific Antibody Treatment for Newly Diagnosed Amyloidosis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Light Chain Amyloidosis
• Intervention / Treatment: Drug: anti-BCMA/CD3 bispecific antibody

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gang An, MD; Phone Number: 13502181109; Email: angang@ihcams.ac.cn

Study Locations

• China
  • Tianjin, China, 300000
    • Recruiting
    • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
    • Contact: Gang AN, PhD&MD; Phone Number: 008613502181109; Email: angang@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BsAbs-treatment group; Treatment involves a 12-cycle course of weekly subcutaneous CM336, with step-up dosing during the first week (3 mg on Day 1, 20 mg on Day 4, and 40 mg weekly from Day 8 onward). Dose frequency may be reduced to every two weeks in patients achieving ≥VGPR after 4 cycles.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Safety will be assessed by monitoring the incidence, nature, and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs) such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), graded according to NCI CTCAE v5.0 and ASTCT criteria. Dose interruptions, modifications, or discontinuations due to toxicity will also be recorded.	From the first dose through 30 days after the last dose, up to approximately 24 months.
Rate of Hematologic Very Good Partial Response (VGPR) or Better	Proportion of participants achieving a hematologic response of VGPR or better (≥VGPR) of anti-BCMA/CD3 bispecific antibody (CM336), assessed using consensus criteria for AL amyloidosis hematologic response.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Hematologic Response (TTR)		From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months.
Best Hematologic Response Achieved	The deepest hematologic response (e.g., PR, VGPR, CR, or sCR) observed at any time during the treatment period.	From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months.
Duration of Hematologic Response (DOR)	Time from the first documented hematologic response to disease progression or death, whichever occurs first.	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 Survival (OS)		From the first dose to death from any cause, up to approximately 36 months.
Overall Response Rate (ORR)		The overall response rate (ORR) was evaluated at the end of cycle 4, 6, and 12 (28 days per cycle).
Progression-Free Survival (PFS)	defined as the time from the date of treatment to the date of first documentation of hematologic disease progression, or organ progression, or death due to any cause.	From the first dose to progression from any cause, up to approximately 36 months.
Minimal Residual Disease (MRD) Negativity Rate	Minimal residual disease (MRD) negativity rate:MRD negativity assessed in bone marrow.	From baseline to 24 months, assessed at predefined response evaluation time points.
Organ Response	Assess Organ Responses Based on Standard Criteria Included in Protocol among patients with organ involvement	12 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 4, 2025
• First Submitted That Met QC Criteria: August 25, 2025
• First Posted (Actual): September 3, 2025

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Light Chain Amyloidosis; BCMA/CD3 bispecific antibody; CM336
• Other Study ID Numbers: IIT2025066

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No