A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL).

NCT07638683 | Recruiting Phase 2 DMC

• 1 other identifier: SHZS-MMAL-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if teclistamab in combination with daratumumab (Tec-Dara) works to treat newly diagnosed multiple myeloma with concurrent light chain amyloidosis (MM+AL). It will also learn about the safety of this combination. The main questions it aims to answer are: Does Tec-Dara improve the 1-year progression-free survival rate compared to historical data (50% to 75%) in MM+AL patients? What are the rates of hematologic response (ORR, VGPR, CR, MRD negativity) and organ response in MM+AL patients treated with Tec-Dara? What medical problems do participants have when taking Tec-Dara? Participants will: Receive teclistamab subcutaneous injection with step-up dosing (0.06, 0.3, 1.5 mg/kg), followed by 1.5 mg/kg weekly in Cycle 1, 3.0 mg/kg every 2 weeks in Cycles 2-3, and 3.0 mg/kg every 4 weeks in Cycles 4-24 Receive daratumumab subcutaneous injection 1800 mg weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and every 4 weeks in Cycles 7-24 Continue treatment until disease progression, unacceptable toxicity, or a maximum of 24 cycles Undergo disease assessments every 28 days (±7 days) including laboratory tests for hematologic and organ response evaluation Provide bone marrow samples for MRD and RNA sequencing analysis

Conditions

Multiple Myeloma; AL Amyloidosis

Keywords

Multiple Myeloma; AL Amyloidosis; Teclistamab; Daratumumab

Outcome Measures

Primary Outcomes (1)

• 1-Year Progression-Free Survival (PFS) Rate

  The percentage of participants who are alive and free from disease progression at 1 year after initiation of Tec-Dara treatment. Progression is defined according to IMWG criteria, including increase in serum M protein, urine M protein, or serum free light chain; development of new bone lesions or soft tissue plasmacytomas; or hypercalcemia.

  From the start of treatment to 1 year, or until disease progression or death, whichever occurs first

Secondary Outcomes (9)

• Hematologic Complete Response (Heme-CR) rate

  Up to 24 cycles (approximately 2 years)

• Very Good Partial Response or Better (≥VGPR) Rate

  Up to 24 cycles (approximately 2 years)

• Minimal Residual Disease (MRD) Negativity Rate

  6 months and 12 months, and up to 24 cycles (approximately 2 years)

• Organ Response Rate

  Up to 24 cycles (approximately 2 years)

• Time to First Response

  Up to 24 cycles (approximately 2 years)

Other Outcomes (1)

• Differential gene expression in bone marrow by RNA sequencing between baseline and disease progression in MM-AL patients.

  Baseline and up to 3 years.

Study Arms (1)

Treatment Group

EXPERIMENTAL

Teclistamab (subcutaneous injection) with step-up dosing: 0.06 mg/kg, 0.3 mg/kg, and 1.5 mg/kg on Days 1, 3, and 5 of Cycle 1, followed by 1.5 mg/kg weekly in Cycle 1, 3.0 mg/kg every 2 weeks in Cycles 2-3, and 3.0 mg/kg every 4 weeks in Cycles 4-24. Daratumumab (subcutaneous injection) 1800 mg weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and every 4 weeks in Cycles 7-24. Treatment continues until disease progression, unacceptable toxicity, or a maximum of 24 cycles (approximately 2 years).

Drug: Teclistamab

Interventions

Teclistamab DRUG

Teclistamab: A humanized IgG4-PAA bispecific antibody targeting BCMA and CD3. It bridges malignant plasma cells and CD3+ T cells, leading to T cell activation and perforin/granzyme-mediated lysis of BCMA+ tumor cells. Daratumumab: A humanized IgG1κ monoclonal antibody targeting CD38, which induces tumor cell lysis through complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis. It also enhances T cell-mediated anti-myeloma immunity by increasing cytotoxic T helper cells and depleting CD38+ immunoregulatory cells, thereby potentiating teclistamab's activity.

Also known as: Daratumumab

Treatment Group

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years, any sex/gender
• Diagnosis of multiple myeloma according to IMWG criteria
• Histopathologic diagnosis of AL amyloidosis confirmed by:
• Green birefringence under polarized light microscopy with Congo red staining; AND at least one of the following:
• Immunohistochemistry and/or immunofluorescence
• Mass spectrometry
• Electron microscopy/immunoelectron microscopy
• Measurable disease at screening
• Newly diagnosed, no prior anti-plasma cell therapy
• Adequate laboratory values:
• Hemoglobin ≥7.5 g/dL
• Absolute neutrophil count ≥1.0×10⁹/L
• Platelet count ≥70×10⁹/L (platelet transfusion acceptable; \>50×10⁹/L if ≥50% bone marrow nucleated cells are plasma cells)
• ALT ≤2.5× upper limit of normal (ULN)
• AST ≤2.5× ULN

You may not qualify if:

• Prior anti-myeloma therapy or stem cell transplantation
• Diagnosis of monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma, primary AL amyloidosis without concurrent MM, Waldenström macroglobulinemia, plasma cell leukemia, POEMS syndrome, or other malignancies within 3 years prior to enrollment
• Active infection or autoimmune disease
• Uncontrolled diabetes, hypertension, or other comorbidities
• Pregnant or lactating female
• Currently participating in another interventional study
• Any other condition that the investigator considers unsuitable for study participation

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Johnson & Johnson: collaborator

Study Sites (1)

Zhongshan Hospital Fudan University

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Peng Liu

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peng Liu

CONTACT

+86-021-64041990; liu.peng@zs-hospital.sh.cn

Jing Li

CONTACT

+86-18149780650; li.jing6@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: June 10, 2026
• Study Start: May 22, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: starting 6 months after publication
• Access Criteria: IPD could be requested by contacting the corresponding author via email after publication.

Locations

CN (1)