A Phase 1/2 Study of a Fully Human BCMA-targeting CAR (CT103A) in Patients With Relapsed/Refractory Multiple Myeloma (FUMANBA-1) (FUMANBA-1)

Phase 1/2 Clinical Study on Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (CT103A) in the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

This study is a single-armed, open-label, multicenter Phase 1/2 study to evaluate the efficacy and safety of CT103A in subjects with relapsed and refractory MM.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: CT103A

Detailed Description

Leukapheresis procedure will be performed to manufacture CT103A chimeric antigen receptor (CAR) modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of CT103A at 1.0 x 10^6 CAR+ T cells/Kg. Subjects will be followed in the study for a minimum of 2 years after CT103A infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after CT103A infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Songbai Cai; Phone Number: +86 025-58287610; Email: simon@iasobio.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University first hospital
  • Beijing, China
    • Recruiting
    • Beijing Boren Hospital
    • Contact: Kai Hu
  • Chongqing, China
    • Recruiting
    • Xinqiao Hospital, Army Medical University
  • Shanghai, China
    • Recruiting
    • Fudan University Zhongshan Hospital
  • Shanghai, China
    • Recruiting
    • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
  • Tianjin, China
    • Recruiting
    • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Provincial Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital
      • Contact: Yongping Song
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
      • Contact: Chunrui Li
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • The Third Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China
      • Recruiting
      • The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital
    • Xuzhou, Jiangsu, China
      • Recruiting
      • The Affiliated Hospital Of XuZhou Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The first Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: He Huang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects must satisfy all the following criteria to be enrolled in the study:

1. age 18 to 70 years old, male or female.
2. Subjects with diagnosed relapsed or refractory MM according to IMWG criteria and have had at least 3 prior lines of therapy including chemotherapy based on proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). Disease progression must be documented during or within 12 months following the most recent anti-myeloma treatment.
3. Evidence of cell membrane BCMA expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue (e.g., bone marrow biopsies, or plasmacytoma).

4. The subjects should have measurable disease based on at least one of the following parameters:

   • The proportion of primitive immature or monoclonal plasma cells detected by bone marrow cytology, bone marrow biopsy, or flow cytometry is ≥ 5%.
   • Serum M-protein ≥ 0.5 g/dL.
   • Urine M-protein ≥ 200 mg/24 hrs.
   • For those whose Serum or Urine M-protein does not meet the measurable criteria but the light chain type, serum free light chain (sFLC): involved sFLC level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
5. ECOG performance score 0-1.
6. Estimated life expectancy ≥ 12 weeks.

7. Patients should have adequate organ function:

   • Hematology: Absolute neutrophil count (ANC) ≥1×10^9 /L (prior use of growth factor support is permitted, but subjects must not have received supportive treatment within 7 days prior to laboratory examination); absolute lymphocyte count (ALC) ≥0.3×10^9 /L; platelets ≥50×10^9 /L (subjects must not have received blood transfusion support within 7 days prior to laboratory examination); hemoglobin ≥60 g/L (subjects must not have received transfusion of red blood cells [RBC] within 7 days prior to laboratory examination; the use of recombinant human erythropoietin is permitted).
   • Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
   • Renal function: Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
   • Coagulation function: Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤ 1.5×ULN.
   • SpO2 > 91%.
   • Left ventricular ejection fraction (LVEF) ≥ 50%.
8. The subject and his/her spouse agree to use an effective contraceptive tool or medication (excluding safety period contraception) for one year from the date of the subject's informed consent to the date of CAR T cell infusion.
9. Subject must sign the informed consent form approved by ethics board in person before starting any screening procedure.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subjects who are known to have GVHD or need long-term immunosuppressive therapy.
2. Subjects have received an autologous hematopoietic stem cell transplantation (auto-HSCT) within 12 weeks before leukapheresis or have a previous history of two times of allo-HSCT or previous history of an allogeneic hematopoietic stem cell transplantation (allo-HSCT).
3. Insufficient mononuclear cells for CAR T cell production.
4. Subjects have received any anti-cancer treatment as follows: targeted therapies, epigenetic therapy or invasive experimental instruments therapy within 14 days or at least 5 half-lives before leukapheresis (according to the longer time), or monoclonal antibody for treating multiple myeloma within 21 days before leukapheresis, or cytotoxic therapy or proteasome inhibitors within 14 days before leukapheresis, or immunomodulatory agents within 7 days before leukapheresis.
5. Subjects who were receiving a used therapeutic dose of corticosteroid treatment (defined as prednisone or equivalent > 20mg) within 7 days prior to screening, except for physiological alternatives, inhalation, or topical use.
6. Subjects with serious heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmias.
7. Subjects with systemic diseases that the investigator determined to be unstable include, but are not limited to, severe liver and kidney or metabolic diseases requiring medical treatment.
8. Subjects with second malignancies in addition to MM within the past 5 years before the screening, exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal or squamous cell skin carcinoma, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast after radical surgery.
9. Subjects with a history of organ transplantation.
10. Subjects have central nervous system (CNS) involvement (including cranial neuropathies or mass lesions and leptomeningeal disease).
11. Subjects with extramedullary lesions (except for a single extramedullary lesion with a maximum transverse diameter of 3 cm).
12. Subjects with plasma cell leukemia.
13. Subjects have received major surgery within 2 weeks prior to leukapheresis or plan to receive surgery during the study or within 2 weeks after the study treatment (excluding local anesthesia).
14. Subjects participated in another interventional clinical study 3 months before signing the informed consent (ICF);
15. Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis collection (excluding < CTCAE grade 2 urogenital infection and upper respiratory infection).

16. Positive for any of the following tests:

    • Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood
    • Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood
    • Human immunodeficiency virus (HIV) antibody
    • Cytomegalovirus (CMV) DNA
    • Treponema Pallidum antibody
17. Pregnant or lactating women.
18. Subjects with mental illness or consciousness disorder or disease of the central nervous system
19. Subjects who haven't recovery to Grade 1 or baseline of any toxicities due to prior treatments, excluding alopecia.
20. Other conditions that researchers consider inappropriate for inclusion.

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: CT103A in relapsed and refractory multiple myeloma patients; CT103A autologous CAR-T cells will be infused at RP2D of 1.0 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy	Drug: CT103A; CT103A consists of autologous T lymphocytes transduced with anti-BCMA CAR lentiviral vector that containing a unique CAR structure with a fully human single-chain variable fragment (scFv).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Incidence and Severity of Adverse Events	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Minimum of 2 years post CT103A infusion
Phase 1: Laboratoty tests	Abnormal results of laboratoty tests	Minimum of 2 years post CT103A infusion
Phase 1: Vital signs	Abnormal results of vital signs	Minimum of 2 years post CT103A infusion
Phase 1: Physical examination	Abnormal results of physical examination	Minimum of 2 years post CT103A infusion
Phase 2: Overall response rate (ORR) evaluated by an Independent Review Committee (IRC)	Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC	3 months post CT103A infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) evaluated by the investigators	Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigators	3 months post CT103A infusion
Overall Survival (OS)	Time from CT103A infusion to time of death due to any cause	Minimum of 2 years post CT103A infusion
Duration of Response (DOR)	Time from first response evaluated by an IRC or investigators to disease progression or death from any cause	Minimum of 2 years post CT103A infusion
Progression-free Survival (PFS)	Time from CT103A infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first	Minimum of 2 years post CT103A infusion
Time to Response (TTR)	Time from CT103A infusion to first documentation of response evaluated by an IRC or investigators	Minimum of 2 years post CT103A infusion
Laboratoty tests	Abnormal results of laboratoty tests	Minimum of 2 years post CT103A infusion
Vital signs	Abnormal results of vital signs	Minimum of 2 years post CT103A infusion
Physical examination	Abnormal results of physical examination	Minimum of 2 years post CT103A infusion
Minimal Residual Disease (MRD)	Proportion of subjects who achieved MRD negative	Minimum of 2 years post CT103A infusion
Pharmacokinetics - Cmax	The maximum transgene level at Tmax	Minimum of 2 years post CT103A infusion
Pharmacokinetics - Tmax	Time to peak transgene level	Minimum of 2 years post CT103A infusion
Pharmacokinetics - AUC0-28days	Area under the curve of CAR T cells from time zero to Day 28	Minimum of 2 years post CT103A infusion
Pharmacokinetics - AUC0-90days	Area under the curve of CAR T cells from time zero to Day 90	Minimum of 2 years post CT103A infusion
soluble BCMA levels	soluble BCMA levels in peripheral blood of subjects	Minimum of 2 years post CT103A infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Development of an anti-CAR antibody response	Minimum of 2 years post CT103A infusion
replication competent lentivirus (RCL)	The incidence of replication competent lentivirus (RCL)	Minimum of 2 years post CT103A infusion
the levels of CAR-T related inflammatory factors	the levels of CRP, IL-6 and Ferritin	Minimum of 2 years post CT103A infusion

Collaborators and Investigators

• Sponsor: Nanjing IASO Biotherapeutics Co.,Ltd
• Investigators: Principal Investigator: Lugui Qiu, MD, PhD, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Principal Investigator: Chunrui Li, MD, PhD, Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: XL-LCYJ-0007

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