Aponermin-Based Bridging Therapy Prior to CAR-T Infusion in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease

Aponermin-Based Bridging Therapy Prior to CAR-T Infusion in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Prospective, Single-Arm, Multicenter, Open-Label Study

This is a prospective, single-arm, multicenter, open-label study to evaluate the efficacy and safety of aponermin-based bridging therapy prior to CAR-T infusion in relapsed/refractory multiple myeloma patients with extramedullary disease.

Study Overview

• Status: Recruiting
• Conditions: Extramedullary Multiple Myeloma
• Intervention / Treatment: Biological: anti-BCMA/GPRC5D bispecific CAR-T; Drug: Apornemin; Drug: Carfilzomib; Drug: Thalidomide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gang An, PhD&MD; Phone Number: 86-022-23909171; Email: angang@ihcams.ac.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing GoBroad Boren Hospital
    • Contact: Wei Chen; Phone Number: 008615801145177; Email: chenwei@gobroadhealthcare.com
  • Tianjin, China
    • 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

Inclusion Criteria:

1. Be informed and voluntarily sign the Informed Consent Form (ICF).
2. Age ≥18 years.
3. Confirmed diagnosis of Multiple Myeloma(MM) (IMWG consensus guidelines)
4. Subjects with diagnosed relapsed or refractory extramedullary multiple myeloma according to IMWG criteria and have had at least 1 prior lines of therapy. Extramedullary disease (EMD) is defined as soft-tissue plasmacytomas NOT arising from skeletal lesions. The maximum diameter of extramedullary lesions should ≥2cm detected by physical exam and confirmed (when required) by Weight Bearing CT/MRI/PET-CT and/or biopsy.
5. ECOG score is ≤ 2
6. No active infections.
7. Negative for HBV-DNA, HCV-RNA, and HIV.
8. Liver function meeting the following criteria: Total bilirubin <1.5 × ULN (patients with Gilbert's syndrome must have total bilirubin <3 × ULN), ALT and AST <3 × ULN.
9. Renal function meeting the following criteria: Creatinine clearance ≥30mL/min (calculated using the Cockcroft-Gault formula).
10. Blood tests conducted within 7 days before screening must meet the following standards: WBC count ≥1.0×10⁹/L, Hemoglobin ≥70g/L, Platelet count ≥75×10⁹/L or ≥50×10⁹/L (if ≥50% plasma cells are present in bone marrow); Or as determined appropriate by the investigator.
11. Patients receiving hematopoietic growth factors (e.g., erythropoietin, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and platelet-stimulating factors such as thrombopoietin [TPO] or interleukin-11) must stop such treatments at least 2 weeks prior to screening.
12. Non-pregnant female patients must confirm pregnancy negativity at screening (via β-hCG serum test or urine pregnancy test).
13. Male patients, female patients of childbearing potential, and their partners must agree to use effective contraception during the treatment period and for at least 3 months after CAR-T cell infusion.
14. Male patients must agree not to donate sperm, starting from the initial screening period until 90 days after the last dose.
15. Patients must agree to comply with study procedures and follow-up visits.

Exclusion Criteria:

1. Plasma cell leukemia or solitary plasmacytoma.
2. Prior exposure to both BCMA- and GPRC5D-targeted therapies (patients who have received only one of these targeted therapies are eligible for enrollment).
3. Evidence of primary or secondary resistance to elotuzumab, carfilzomib, or thalidomide.
4. Pregnant or breastfeeding women, or women with pregnancy plans within the next six months.
5. Infectious diseases (e.g., HIV, active tuberculosis, etc.).
6. Active hepatitis B or hepatitis C infection.
7. Abnormal vital signs or inability to cooperate with examinations.
8. Mental or psychological disorders preventing compliance with treatment or treatment evaluation.
9. Severe allergic constitution or severe allergic history, particularly to aponermin, carfilzomib, thalidomide, dexamethasone or other effective components or excipients of related drugs.
10. Significant dysfunction of major organs, such as the heart, lungs, or brain.

9) Patients with severe autoimmune diseases. 11) Any other reasons deemed unsuitable for participation in this study as determined by the investigator.

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: Aponermin-based regimen bridging CAR-T therapy; Patients will receive aponermin-based bridging therapy followed by Fc-based conditioning and CAR-T cell infusion. One month after CAR-T cell therapy, patients will begin maintenance therapy for at most 6 months or until disease progression, death, intolerance, withdrawal for other reasons, or the study's termination/completion.

Biological: anti-BCMA/GPRC5D bispecific CAR-T; Autologous BCMA/GPRC5D bispecific CAR-T cells, infusion intravenously at a target dose of 2-4 x 10^6 anti-BCMA/GPRC5D bispecific CAR-T cells/kg.; Drug: Apornemin; Apornemin 10mg/kg will be administered by i.v. infusion. Apornemin will be administered on Days 1-5, 15-19 during bridging therapy, and on Days 1-5 every 28-day cycle during maintanance treatment.; Drug: Carfilzomib; Carfilzomib 27mg/m^2 will be administered by i.v. on Days 1,2,8,9 during bridging therapy.; Drug: Thalidomide; Thalidomide (150mg/d) will be administered by p.o. on Days 1-14 during bridging therapy, and Days 1-28 every 28-day cycle during maintanance treatment.; Drug: Dexamethasone; Dexamethasone (20mg/d) will be administered by i.v. or p.o. on Days 1-4,8,9 during bridging therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The definition of ORR is the proportion of participants who achieve a PR or better as the best response according to the IMWG criteria.	within 1 months after BCMA/GPRC5D CAR-T infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR before CAR-T cell infusion	ORR before CAR-T cell infusion is defined as the proportion of participants who achieve a confirmed PR or better as the best response after conditioning treatment but prior to CAR-T cell infusion.	before CAR-T cell infusion
Progression free survival(PFS)	Progression free survival is defined as the time from the start of Aponermin treatment to disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.	Up to 2 year
Overall Survival (OS)	Overall Survival (OS) is defined as the time from the start of Aponermin treatment to the date of the participant's death.	Up to 2 year
Adverse events and serious adverse events	Adverse events (AEs), serious adverse events (SAEs), and assessments of clinical laboratory values	Up to 2 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: January 21, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Leprostatic Agents; Dexamethasone; Thalidomide
• Other Study ID Numbers: IIT2024113

Drug and device information, study documents

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