BCMA/GPRC5D Trispecific Antibody Treatment for Newly Diagnosed Amyloidosis (AL-004)

NCT07751471 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT2026034
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Systemic light-chain (AL) amyloidosis is a plasma cell disorder characterized by the production of misfolded immunoglobulin light chains that deposit in organs and lead to progressive organ dysfunction. Although daratumumab-based therapy has improved outcomes, a substantial proportion of patients fail to achieve deep hematologic responses. This is a prospective, single-arm, single-center clinical study evaluating the safety and efficacy of the BCMA/GPRC5D/CD3 trispecific antibody QLS4131 in patients with newly diagnosed systemic AL amyloidosis.

Conditions

AL Amyloidosis

Keywords

QLS4131; Systemic Light Chain Amyloidosis; BCMA/GPRC5D/CD3 trispecific antibody; Plasma cell disorder

Outcome Measures

Primary Outcomes (1)

• Hematologic Complete Response (CR) Rate

  Proportion of participants achieving hematologic complete response (CR) according to the International Society of Amyloidosis (ISA) response criteria following treatment with QLS4131.

  At the end of each 28-day treatment cycle and before the start of the next cycle, through Cycle 8 （each cycle is 28 days)

Secondary Outcomes (7)

• time to hematologic response

  From the first dose until the first documented response, assessed every 2 weeks in Cycle 1 and every 28 days from Cycle 2 through end of treatment (each cycle is 28 days)

• Duration of Hematologic Response (DOR)

  From first documented response until disease progression or death, assessed up to 2 years

• Overall Hematologic Response Rate (ORR)

  From first dose through end of treatment, assessed every 28 days

• Minimal residual disease (MRD) negativity rate

  Bone marrow MRD assessed at the time of suspected hematologic complete response (CR) or dFLC <10 mg/L, up to the end of treatment from first dose

• Progression-Free Survival (PFS)

  From first dose until disease progression or death, assessed up to 2 years

Study Arms (1)

QLS4131-treatment group

EXPERIMENTAL

Drug: QLS4131

Interventions

QLS4131 DRUG

QLS4131 is an investigational GPRC5D/BCMA/CD3 trispecific antibody administered by subcutaneous injection. The study uses a step-up dosing schedule followed by full-dose maintenance treatment over 6 to 8 treatment cycles. Supportive care and prophylactic medications for cytokine release syndrome (CRS) are permitted according to the study protocol.

QLS4131-treatment group

Eligibility Criteria

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

You may qualify if:

• Voluntarily provide written informed consent (ICF) prior to any study-specific procedures.
• Age ≥18 years, regardless of sex.
• Newly diagnosed primary systemic light-chain (AL) amyloidosis.
• Measurable disease at screening, defined as:
• Difference between involved and uninvolved serum free light chains (dFLC) ≥20 mg/L; and
• Abnormal serum free light chain (FLC) ratio or other confirmed evidence of monoclonal light chain production.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Adequate organ function within 3 days before the first administration of the investigational product:
• i. Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L, without treatment with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 7 days, and without pegylated G-CSF within 14 days before dosing.
• ii. Hemoglobin ≥75 g/L without whole blood or red blood cell transfusion within 7 days before dosing.
• iii. Platelet count ≥70 × 10⁹/L without platelet transfusion, whole blood transfusion, or thrombopoietin receptor agonists within 7 days before dosing.
• iv. Hepatic function:
• ALT ≤3 × upper limit of normal (ULN);
• AST ≤3 × ULN;
• Total bilirubin ≤2 × ULN. Participants with Gilbert syndrome may be enrolled if direct bilirubin is ≤2 × ULN.

You may not qualify if:

• Non-AL amyloidosis, including hereditary amyloidosis or any other non-AL subtype.
• Symptomatic multiple myeloma.
• Grade \>2 peripheral neuropathy or Grade ≥2 painful peripheral neuropathy at screening, regardless of current treatment.
• History of another malignancy within 5 years before enrollment, except AL amyloidosis.
• Prior anti-plasma cell therapy, including:
• Melphalan
• Cyclophosphamide
• Proteasome inhibitors
• Immunomodulatory drugs (IMiDs)
• Monoclonal antibodies
• Bispecific antibodies
• Trispecific antibodies
• Autologous stem cell transplantation
• Chimeric antigen receptor (CAR)-T cell therapy
• Exceptions include:

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, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Neoplasms, Plasma Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Central Study Contacts

Gang an, MD

CONTACT

022-23909083; angang@ihcams.ac.cn

jieqiong zhou, PhD

CONTACT

zhoujieqiong@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: July 21, 2026
• First Posted: August 7, 2026
• Study Start: July 20, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 7, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)