BCMA/CD3 Bispecific Antibody Treatment for Newly Diagnosed Amyloidosis

NCT07151690 | Recruiting Phase 2

• 1 other identifier: IIT2025066
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Light Chain Amyloidosis

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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.

Secondary Outcomes (8)

• 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

  From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months.

• Duration of Hematologic Response (DOR)

  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)

  The overall response rate (ORR) was evaluated at the end of cycle 4, 6, and 12 (28 days per cycle).

• Progression-Free Survival (PFS)

  From the first dose to progression from any cause, up to approximately 36 months.

Study Arms (1)

BsAbs-treatment group

EXPERIMENTAL

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

Interventions

anti-BCMA/CD3 bispecific antibody DRUG

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.

BsAbs-treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (1)

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, 300000, China

RECRUITING

Central Study Contacts

Gang An, MD

CONTACT

13502181109; angang@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2025
• First Posted: September 3, 2025
• Study Start: September 4, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

CN (1)