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

Multiple Myeloma Clinical Trial

— FUMANBA-03  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06464991
• Other study ID #: CT103AC004
• Status: Recruiting
• Phase: Phase 3
• Start date: March 27, 2024
• Est. completion date: December 2030

Study information

• Verified date: June 2024
• Source: Nanjing IASO Biotechnology Co., Ltd.
• Contact: Yue Wan
• Phone: +86 025-58287610
• Email: yue.wan[@]iasobio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 2030
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1.18 to 70 years of age (inclusive of cutoff), regardless of gender. 2. Subjects were previously diagnosed with multiple myeloma and received 1-2 lines of proteasome inhibitor and immunomodulatory-based chemotherapy, with at least one complete cycle of each line of treatment; Documented disease progression during or within 12 months after the most recent anti-myeloma therapy.

3. Subjects were previously refractory to lenalidomide treatment. 4.ECOG score of 0 or 1.

5. Subjects must have adequate organ function and meet all the following laboratory test results before enrollment: ? Blood routine: absolute neutrophil count (ANC) =1×10^9/L (growth factor support allowed, but no supportive treatment within 7 days before laboratory test); Absolute lymphocyte count (ALC) =0.3×10^9/L; Platelet count =50×10^9 / L (no supportive platelets infusion allowed within 7 days before lab test ); Hemoglobin =60g/L (no transfusion of red blood cells [RBC] within 7 days before the laboratory test; the use of recombinant human erythropoietin was allowed); (2) liver 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 according to Cockcroft - Gault formula of creatinine clearance (CrCl) should be =40 ml/min; ? Coagulation function: fibrinogen =1.0g/L; aPTT=1.5 x ULN, prothrombin time (PT)=1.5 x ULN; ? oxygen saturation>91%; ? 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. Before starting any screening program, subjects must have to agreed to sign or sign the informed consent in person which have been approved by the ethics committee.

Exclusion Criteria:

1. Subjects who have used or need long-term use of immunosuppressive agents, such as cyclosporine or systemic steroid) 14days before enrollment; but the use of physiological substitute, intermittent, local and inhaled steroids is allowed.

2. Patients who had undergone autologous hematopoietic stem-cell transplantation (Auto-HSCT) within 12 weeks before randomization or prior allogeneic hematopoietic stem-cell transplantation (Allo-HSCT);

3. The subject received the following anti-tumor therapy before enrollment: ? immunomodulatory therapy within 7 days, or; ? Plasma exchange, radiotherapy (except for local radiotherapy for myeloma-associated bone lesions), cytotoxic chemotherapy, proteasome inhibitor, or other investigation drug in clinical trial within 14 days; or (3) monoclonal antibody treatment for multiple myeloma within 21 days, or; (4) within 14 days or at least five half-life (will be subject to a shorter time) of other anti-tumor treatment except for the above-mentioned ones;

4. Severe heart disease;

5. Unstable Systemic diseases per investigator's evaluation: including, but not limited to, severe hepatic, renal, or metabolic diseases requiring medical treatment;

6. subjects with the following conditions per investigator's evaluation will not be able to participate in the study: (1) allergic to excipients of Equecabtagene Autoleucel Injection (DMSO and albumin), fludarabine, cyclophosphamide, tocilizumab, or; ? subjects intolerant to dexamethasone, or; (3) subjects who have life-threatening allergy, allergic reactions, or intolerance (intolerance is defined as end of treatment for any pomalidomide related AE) with pomalidomide, or; ? subjects who met the NCI-CTCAE v5.0 definition of grade 2 peripheral neuropathy with pain or = grade 3 peripheral neuropathy;

7. Diagnosed with another malignancy within 5 years before screening except for multiple myeloma, excluding radical cervical carcinoma in situ, basal cell or squamous epithelial cell skin cancer, radical localized prostate cancer, radical ductal carcinoma in situ of the breast, or papillary thyroid cancer;

8. Patients with suspected or existed central nervous system involvement of plasma cell neoplasms during screening;

9. subjects with plasma cell leukemia (defined as > 5% peripheral plasma cells), Waldenstrom macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and cutaneous changes), or primary amyloidosis previously or during screening period;

10. Multiple myeloma patients with extramedullary lesions (except for a single parosteal extramedullary lesion =3cm in maximum transverse diameter)

11. Subject who underwent major surgery within 2 weeks before randomization or have surgery plan within 2 weeks after study treatment (except for those scheduled surgery under local anesthesia);

12. Subject with uncontrollable infection;

13. The hepatitis b surface antigen (HBsAg) or hepatitis b core antibody (HBcAb) positive with hepatitis b virus (HBV) DNA quantification higher than the detection limit; Hepatitis C virus (HCV) antibody positive with HCV RNA positive in peripheral blood; human immunodeficiency virus (HIV) antibody positive; Syphilis testing positive;

14. Women who are pregnant or lactating;

15. The subject has a existed central nervous system disease or with medical history of CNS disease;

16. Non-hematologic toxicity due to prior therapy havn't been resolved to baseline or = grade 1 (NCI-CTCAE version 5.0, excluding alopecia and grade 2 peripheral neuropathy)

17. The subject had other conditions unsuitable for enrollment per investigator's evaluation.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Equecabtagene Autoleucel Injection
dosage form: injection, dosage: 1.0×10^6 CAR-T/kg, frequency: single dose.
• 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
• Pomalidomide
dosage form:capsule. doseage form: capsule. dose level: 4mg/d. frequency: every cycle: D1-D21 for DPd regimen, D1-D14 for PVd regimen.
• 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.
• 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.

Locations

Country	Name	City	State
China	Beijing Chao-Yang Hospital, Capital Medical University	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	People's Hospital of Peking University	Beijing
China	The first hospital of Jilin University	Chang chun
China	West China School of Medicine, West China Hospital of Sichuan University	Chengdu
China	Xinqiao Hospital of AMU	Chongqing
China	Nanfang Hospital, Southern Medical University	Guangzhou
China	Sun Yat-sen University Cancer Centre	Guangzhou
China	Zhujiang Hospital of Southern Medical University Guangdong	Guangzhou
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	The Second Affiliated Hospital,Zhejiang University School of Medicine	Hangzhou
China	Qilu Hospital of Shangdong University	Jinan
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Affiliated Drum Tower Hospital, Medical School of Nanjing University	Nanjing
China	Jiangsu Province Hospital	Nanjing
China	The Affiliated People's Hospital of Ningbo University	Ningbo
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou
China	Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjing
China	Tianjin Medical University General Hospital	Tianjing
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan
China	Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan
China	Henan Cancer Hospital Affilated Cancer Hospital of Zhengzhou University	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Nanjing IASO Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival per independent review committee, PFS per IRC	The time from randomization to the first time of documented disease progression or death from any cause per IRC	up to 5 years from randomization
Secondary	Minimal Residual Disease Negativity Rate	Proportion of subjects with MRD-negative bone marrow detection by next-generation flow cytometry following study therapy	up to 5 years from randomization
Secondary	Duration of MRD negativity	The time from the first MRD negative to the first MRD negative positive transfer	up to 5 years from randomization
Secondary	Complete Response rate	Proportion of subjects who achieved CR or better response after receiving study therapy	up to 5 years from randomization
Secondary	Rate of very good partial response or better	Proportion of subjects who achieved strict complete response (sCR), CR, and VGPR after receiving study therapy	up to 5 years from randomization
Secondary	Overall Response Rate	Proportion of subjects who achieved sCR, CR, VGPR, and PR after receiving study therapy	up to 5 years from randomization
Secondary	Event Free Survival	The time from the start of randomization until the first occurrence of any of the following events, including death, disease progression, change of treatment, addition of another treatment, fatal or intolerable side effects	up to 5 years from randomization
Secondary	Overall Survival	The time from randomization until death from any cause	up to 5 years from randomization
Secondary	Time to Next Treatment	The time from receipt of the trial drug to initiation of the next line of treatment	up to 5 years from randomization
Secondary	incidence of Adverse events	Safety Endpoint	up to 5 years from randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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