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).

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)

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

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; AL Amyloidosis
• Intervention / Treatment: Drug: Teclistamab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Liu; Phone Number: +86-021-64041990; Email: liu.peng@zs-hospital.sh.cn
• Study Contact Backup: Name: Jing Li; Phone Number: +86-18149780650; Email: li.jing6@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Zhongshan Hospital Fudan University
    • Contact: Jing Li; Phone Number: +86-18149780650; Email: li.jing6@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years, any sex/gender
2. Diagnosis of multiple myeloma according to IMWG criteria

3. Histopathologic diagnosis of AL amyloidosis confirmed by:

   • Green birefringence under polarized light microscopy with Congo red staining; AND at least one of the following:

     1. Immunohistochemistry and/or immunofluorescence
     2. Mass spectrometry
     3. Electron microscopy/immunoelectron microscopy
4. Measurable disease at screening
5. Newly diagnosed, no prior anti-plasma cell therapy

6. 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
   • Total bilirubin ≤2.0× ULN
   • Creatinine clearance ≥30 mL/min
   • Corrected serum calcium ≤14 mg/dL
7. Male and female participants of childbearing potential must use at least 2 effective contraceptive methods during the study
8. Voluntarily signed informed consent form (ICF)

Exclusion Criteria:

1. Prior anti-myeloma therapy or stem cell transplantation
2. 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
3. Active infection or autoimmune disease
4. Uncontrolled diabetes, hypertension, or other comorbidities
5. Pregnant or lactating female
6. Currently participating in another interventional study
7. Any other condition that the investigator considers unsuitable for study participation

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: Treatment Group; 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; 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.; Other Names: Daratumumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic Complete Response (Heme-CR) rate	Heme-CR will be defined as: involved free light-chain level less than the upper limit of the normal range with negative serum and urine immunofixation; normalization of the uninvolved free light-chain level or free light-chain ratio will not be required to determine a complete response. Heme-CR rate is the percentage of participants who achieve CR prior to subsequent anti-myeloma therapy, during or after the study treatment.	Up to 24 cycles (approximately 2 years)
Very Good Partial Response or Better (≥VGPR) Rate	Heme-VGPR is defined as a reduction in the dFLC to <40 mg/L. ≥VGPR rate is the percentage of participants achieving VGPR and CR prior to subsequent anti-myeloma therapy during or after the study treatment.	Up to 24 cycles (approximately 2 years)
Minimal Residual Disease (MRD) Negativity Rate	Proportion of participants achieving MRD negativity at a sensitivity threshold of 10^-5, assessed by next-generation flow cytometry (NGF) or next-generation sequencing (NGS). The MRD-negativity rate by 6 and 12 months will be reported descriptively.	6 months and 12 months, and up to 24 cycles (approximately 2 years)
Organ Response Rate	Proportion of participants achieving organ response according to consensus criteria for AL amyloidosis, based on changes in NT-proBNP, cardiac troponin T/I, and estimated glomerular filtration rate (eGFR).	Up to 24 cycles (approximately 2 years)
Time to First Response	Time from the start of treatment to the first documented PR or better response according to IMWG criteria.	Up to 24 cycles (approximately 2 years)
Duration of Response	Time from the start of treatment to death from any cause.	Up to 3 years from study start
Median Progression-Free Survival	Time from the start of treatment to disease progression or death from any cause, whichever occurs first.	Up to 3 years from study start
Time to Next Treatment	Time from the start of treatment to the initiation of first subsequent anti-myeloma therapy.	Up to 3 years from study start
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0. A participant with multiple adverse events of the same preferred term will be counted once. Adverse events will be summarized by frequency, severity (graded by CTCAE v5.0), and causality, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, hematologic toxicities, and infusion-related reactions.	Through study completion, up to 12 months after the end of study treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential gene expression in bone marrow by RNA sequencing between baseline and disease progression in MM-AL patients.	Bone marrow transcriptome profiles will be analyzed by RNA sequencing at baseline and at disease progression to identify differentially expressed genes, altered signaling pathways, and molecular signatures predictive of disease progression in MM-AL patients. Data will be summarized as fold-change in gene expression, pathway enrichment scores, and predictive model performance metrics (e.g., AUC, sensitivity, specificity).	Baseline and up to 3 years.

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Johnson & Johnson
• Investigators: Principal Investigator: Peng Liu, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): May 22, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Daratumumab; Teclistamab; AL Amyloidosis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Proteostasis Deficiencies; Amyloidosis; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma; daratumumab
• Other Study ID Numbers: SHZS-MMAL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication
• IPD Sharing Time Frame: starting 6 months after publication
• IPD Sharing Access Criteria: IPD could be requested by contacting the corresponding author via email after publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No