A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03) (FUMANBA-03)

A Phase III Randomized, Controlled Study of Equecabtagene Autoleucel Injection in Subjects With Lenalidomide-Refractory R/R Multiple Myeloma

This is a multicenter, randomized, controlled, open-label, phase III clinical study to evaluate the efficacy of Equecabtagene Autoleucel Injection versus standard therapy in subjects with lenalidomid-refractory RRMM who have received 1-2 lines of prior therapy.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Equecabtagene Autoleucel Injection; Drug: Daratumumab; Drug: Pomalidomide; Drug: Bortezomib; Drug: Dexamethasone

Detailed Description

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accounts for more than 10%-20% of hematologic malignancies worldwide, leading to marrow failure and bone destruction. Equecabtagene Autoleucel (eque-cel) is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), which expressed on both mature B lymphocytes and malignant plasma cells. The primary objective for this study is to compare the efficacy of eque-cel versus standard therapy in lenalidomid-refractory RRMM. Subjects will undergo screening with informed consent. After enrollment, randomization will be conducted followed by study treatment in experimental or control group. A follow-up phase will include assessments for safety, efficacy evaluation and pharmacokinetics monitoring (experimental arm) . The duration of this trial is about 6 years.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yue Wan; Phone Number: +86 025-58287610; Email: yue.wan@iasobio.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital
    • Contact: Hongmei Jing
  • Beijing, China
    • Recruiting
    • Beijing Chao-yang Hospital, Capital Medical University
    • Contact: WenMing Chen
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Jian Li
  • Beijing, China
    • Recruiting
    • Peking University First Hospital
    • Contact: YuJun Dong
  • Beijing, China
    • Recruiting
    • People's Hospital of Peking University
    • Contact: Jin Lu
  • Beijing, China
    • Recruiting
    • Beijing GoBoard Boren Hospital
    • Contact: Gang An
  • Beijing, China
    • Recruiting
    • Fu Xing Hospital, Capital Medical University
    • Contact: Jin Lu
  • Chang chun, China
    • Recruiting
    • The First Hospital of Jilin University
    • Contact: FengYan Jin
  • Chengdu, China
    • Recruiting
    • West China School of Medicine, West China Hospital of Sichuan University
    • Contact: WenJiao Tang
  • Chongqing, China
    • Recruiting
    • Xinqiao Hospital of AMU
    • Contact: YunJing Zeng
  • Guangzhou, China
    • Recruiting
    • Nanfang Hospital, Southern Medical University
    • Contact: XiaoLei Wei
  • Guangzhou, China
    • Recruiting
    • Sun Yat-Sen University Cancer Centre
    • Contact: Zhongjun Xia
  • Guangzhou, China
    • Recruiting
    • Zhujiang Hospital of Southern Medical University Guangdong
    • Contact: YanJie He
  • Hangzhou, China
    • Recruiting
    • The First Affiliated Hospital, College of Medicine, Zhejiang University
    • Contact: Zhen Cai
  • Hangzhou, China
    • Recruiting
    • The Second Affiliated Hospital,Zhejiang University School of Medicine
    • Contact: WenBin Qian
  • Jinan, China
    • Recruiting
    • Qilu Hospital of Shangdong University
    • Contact: LuQun Wang
  • Nanchang, China
    • Recruiting
    • The First Affiliated Hospital of NanChang University
    • Contact: Fei Li
  • Nanjing, China
    • Recruiting
    • Jiangsu Province Hospital
    • Contact: LiJuan Chen
  • Nanjing, China
    • Recruiting
    • Affiliated Drum Tower Hospital, Medical School of Nanjing University
    • Contact: Bin Chen
  • Ningbo, China
    • Recruiting
    • The Affiliated People's Hospital of Ningbo University
    • Contact: Ying Lu
  • Shanghai, China
    • Recruiting
    • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
    • Contact: Jianqing Mi
  • Suzhou, China
    • Recruiting
    • The First Affiliated Hospital of Soochow University
    • Contact: ChengCheng Fu
  • Tianjing, China
    • Recruiting
    • Tianjin Medical University General Hospital
    • Contact: Rong Fu
  • Tianjing, China
    • Recruiting
    • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
    • Contact: LuGui Qiu, PhD
  • Wenzhou, China
    • Recruiting
    • The First Affiliated Hospital of Wenzhou Medical University
    • Contact: Songfu Jiang
  • Wuhan, China
    • Recruiting
    • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Contact: ChunRui Li
  • Wuhan, China
    • Recruiting
    • Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
    • Contact: Heng Mei
  • Zhengzhou, China
    • Recruiting
    • Henan Cancer Hospital Affilated Cancer Hospital of Zhengzhou University
    • Contact: Baijun Fang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 18 to 75 years of age (inclusive of critical values), either gender.
2. The subject was previously diagnosed with multiple myeloma and had received 1-2 lines of therapy (including chemotherapy regimens based on proteasome inhibitors and immunomodulatory agents, with each line of therapy receiving at least 1 full cycle ; Documented disease progression during or within 12 months after the most recent anti-myeloma therapy.
3. Subjects was lenalidomide-refractory during prior therapy.
4. ECOG score of 0 or 1.
5. Subjects must have appropriate organ function and meet all of the following laboratory test results before enrollment:

(1) Haematology: absolute neutrophil count (ANC) ≥1×10^9/L (support with growth factor is allowed, but must not have received supportive treatment within 7 days before the laboratory test); Absolute lymphocyte count (ALC) ≥0.3×10^9/L; Platelets ≥50×10^9 / L (must not have received platelet transfusion within 7 days prior to laboratory test); Hemoglobin ≥60g/L (must not have received red blood cells transfusion within 7 days prior to laboratory test); (2) Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times of upper limit of normal (ULN); Serum total bilirubin ≤1.5 times of ULN; (3) Renal function: creatinine clearance (CrCl) calculated by Cockcroft-Gault formula ≥ 40 ml/min; (4) Coagulation: fibrinogen≥1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, pro-thrombin time (PT) ≤ 1.5 × ULN; (5) Pulse oxygen saturation > 91%; (6) Left ventricular ejection fraction (LVEF)≥50%;

6. Subjects agree to use effective tools or drug contraception (excluding safe period contraception) after signing the informed consent form.

7. Subjects must agree to sign or personally sign an ethics committee-approved informed consent form before starting any screening procedures.

Exclusion Criteria:

1. Subjects who have used or required long-term immune-suppressive agents (e.g., cyclosporine or systemic steroids) within 14 days prior to enrollment, but the use of physiological substitutes, intermittent, topical, and inhaled steroids is allowed.
2. Subjects who have undergone autologous haematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks prior to randomization, or who have previously undergone allogeneic haematopoietic stem cell transplantation (Allo-HSCT).
3. Subjects received the following anti-tumor treatments before enrollment: (1)Treated with an immunomodulator within 7 days, or; (2)Received plasma exchange, radiotherapy (except local radiotherapy for myeloma-related bone lesions), cytotoxic chemotherapy, treatment with proteasome inhibitors or other investigational drug within 14 days, or; (3) Treatment with monoclonal antibody for multiple myeloma within 21 days, or; (4) Received other anti-cancer therapy within 14 days or at least 5 half-lives (whichever is shorter) prior to enrollment.
4. Significant cardiac disorder.
5. Unstable systemic disease as judged by the investigator: including but not limited to severe liver, renal, or metabolic disease requiring medication.
6. The subject will not be able to participate in this study if the investigator determines that the subject meets any of the following conditions: (1) Subjects with a history of allergic reaction to the excipient components (DMSO and albumin) of Eque-cel, fludarabine, cyclophosphamide, tocilizumab, or; (2) Subjects who are intolerant to dexamethasone, or; (3) Subjects who have a Life-threatening allergy, hypersensitivity reaction, or intolerance to pomalidomide and/or its excipients (intolerance is defined as discontinuation of prior treatment due to any AE related to pomalidomide) or;
7. Have malignancies other than multiple myeloma within 5 years before screening, excluding cervical carcinoma in situ after radical surgery, basal cell or squamous cell skin cancer, localized cancer of prostate after radical prostatectomy, breast ductal carcinoma in situ after radical mastectomy or carcinoma papillary thyroid after radical thyroidectomy.
8. Subjects suspected or confirmed to have central nervous system involvement of MM during the screening period.
9. Subjects with concurrent plasma cell leukemia(defined as plasma cell proportion in peripheral blood > 5%), Waldenström macroglobulinaemia, POEMS syndrome (polyneuropathy, organ hypertrophy, endocrinopathy, monoclonal protein and skin changes) or primary amyloidosis during screening period.
10. Have extramedullary multiple myeloma-extraosseous (EM-E); have multiple extramedullary multiple myeloma-bone related (EM-B) and the maximum transverse diameter of any lesion is >3cm; have a single EM-B and the maximum transverse diameter of the lesion is >3cm.
11. Had major surgery within 2 weeks prior to randomization or planned to have surgery within 2 weeks after study treatment (except for subjects who were scheduled to have surgery under local anesthesia).
12. Subject with uncontrollable infection.
13. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and hepatitis B virus (HBV) DNA quantification in peripheral blood was higher than the lower limit of detection; hepatitis C virus (HCV) antibody positive and hepatitis C virus (HCV) RNA positive in peripheral blood; Human immunodeficiency virus (HIV) antibody positive; Syphilis test positive; positive cytomegalovirus (CMV) DNA.
14. Pregnant or breastfeeding women.
15. The subject has a history of central nervous system disorder within 6 months prior to signing the informed consent form.
16. Non-hematological toxicity reactions due to prior treatment have not resolved to baseline or ≤ Grade 1 (NCI-CTCAE v5.0, alopecia, Grade 2 peripheral neuropathy were excepted).
17. Subjects had other conditions that the investigator considered unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Drug:Equecabtagene Autoleucel Injection	Drug: Equecabtagene Autoleucel Injection; dosage form: injection, dosage: 1.0×10^6 CAR-T/kg, frequency: single dose.; Other Names: FUCASO
Active Comparator: Control group; Drug: Daratumumab, Bortezomib, Dexamethasone, Pomalidomide, DPd group: Daratumumab, Pomalidomide, Dexamethasone PVd group: Bortezomib, Dexamethasone, Pomalidomide	Drug: Daratumumab; dosage form: Injection dose level:16mg/kg frequency: 28days/cycle for DPd regimen; Cycle1-2：D1, D8, D15, D22；; Cycle3-6：D1, D15；; above Cycle7：D1; Drug: Pomalidomide; dosage form:capsule. doseage form: capsule. dose level: 4mg/d. frequency: every cycle: D1-D21 for DPd regimen, D1-D14 for PVd regimen.; Drug: Bortezomib; dosage form: subcutaneous injection. dose level: 1.3mg/m2. frequency: 21days/cycle for PVd regimen cycle 1-8: D1,D4, D8, D11； above cycle 9: D1, D8.; Drug: Dexamethasone; dosage form: oral or intravenus injection. dose level:20mg/d. frequency: for DPd: every cycle, D1, D2, D8, D9, D15, D16, D22, D23； for PVd: Cycle1-8：D1, D2, D4, D5, D8, D9, D11, D12; above Cycle 9: D1, D2, D8, D9.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) as assessed by Independent Review Committee (IRC)	The time from randomization to the first documented disease progression as determined by IRC or death due to any cause	up to 5 years from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Endpoint-Cmax	The maximum concentration (Cmax) of CAR VCN and BCMA CAR-T in peripheral blood after CAR-T infusion	up to 5 years from Eque-cel infusion
Pharmacokinetic Endpoint-Tmax	the time for CAR VCN and BCMA CAR-T to reach the maximum concentration (Tmax) after CAR-T infusion	up to 5 years from Eque-cel infusion
Pharmacokinetic Endpoint-AUC	Area under the curve of 29, 85, 169 days and the last time point of PK detection (AUC0-29d, AUC0-85d, AUC0-169d, AUC0-last) for CAR VCN; Area under the curve of 29 days (AUC0-29) for BCMA CAR-T.	up to 5 years from Eque-cel infusion
Pharmacodynamic Endpoint	The concentration of soluble BCMA in peripheral blood of experimental group at each time point	up to 5 years from Eque-cel infusion
Health Related Quality of Life Endpoint	Symptoms, function, and overall HRQoL were collected using the validated Patient-Reported Outcomes (PRO) questionnaire	up to 5 years from randomization
Minimal Residual Disease (MRD) negativity rate at 12 months	The proportion of subjects who achieve MRD negativity (using next-generation flow cytometry according to EuroFlow standard operating procedures) and complete response (CR) or better, as assessed by IRC, 12 months (±3 months) post-randomization	up to 5 years from randomization
Overall MRD negativity rate	The proportion of subjects who achieve MRD negativity at any time after the date of randomization and before the initiation of subsequent therapy	up to 5 years from randomization
Duration of MRD negativity	The time from first achievement of MRD negativity to the first subsequent positive MRD status	up to 5 years from randomization
Complete Response Rate（CRR）	The proportion of subjects who achieve CR or better post-randomization among all randomized subjects	up to 5 years from randomization
Very good partial response or better response (≥VGPR) rate	The proportion of subjects who achieve sCR, CR, or VGPR post-randomization among all randomized subjects	up to 5 years from randomization
Overall Response Rate（ORR）	The proportion of subjects who achieve sCR, CR, VGPR, or PR post-randomization among all randomized subjects.	up to 5 years from randomization
Duration of Response (DOR)	The time from the first date of initial documented response (≥PR) to the date of first disease progression or death from any cause, whichever occurs first, post-randomization	up to 5 years from randomization
Event-Free Survival (EFS)	Time from randomization to the first occurrence of any of the following events: death, disease progression, initiation of a new anti-myeloma therapy, addition of other treatments, or occurrence of fatal or intolerable adverse effects	up to 5 years from randomization
Overall Survival（OS）	Defined as the time from randomization to death due to any cause	up to 5 years from randomization
Time to Next Treatment（TTNT）	Time from randomization to the initiation of a new subsequent anti-myeloma therapies	up to 5 years from randomization
Incidence of Adverse events	Safety Endpoint	up to 5 years from randomization

Collaborators and Investigators

• Sponsor: Nanjing IASO Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Gui Lu Qiu, PhD, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences; Principal Investigator: Zhen Cai, PhD, First affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: May 30, 2024
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): July 20, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Eque-cel
• 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; Antineoplastic 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; Bortezomib; Dexamethasone; Pomalidomide; Daratumumab
• Other Study ID Numbers: CT103AC004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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