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

NCT05698303 | Unknown Phase 1 FDA Drug

• 1 other identifier: CT103AA001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

It is a dose expansion, open-label, phase Ib study to evaluate the safety, efficacy, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of CT103A in patients with relapsed/refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

relapsed/refractory multiple myeloma; RRMM; CAR-T; BCMA

Outcome Measures

Primary Outcomes (3)

• Incidence and severity of adverse events

  An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS).

  Up to 2 years after CT103A infusion.

• Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)

  CRS and ICANS will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.

  Up to 2 years after CT103A infusion.

• Number of participants with laboratory abnormalities

  Number of participants with laboratory abnormalities will be reported.

  Up to 2 years after CT103A infusion.

Secondary Outcomes (10)

• Overall response rate (ORR)

  Up to 2 years after CT103A infusion.

• Progression-free survival (PFS)

  Up to 2 years after CT103A infusion.

• Overall survival (OS)

  Up to 2 years after CT103A infusion.

• Duration of response (DOR)

  Up to 2 years after CT103A infusion.

• Time to response (TTR)

  Up to 2 years after CT103A infusion.

Other Outcomes (3)

• CAR-positive cell counts in peripheral blood.

  Up to 2 years after CT103A infusion.

• Presence of human anti-CAR antibodies

  Up to 2 years after CT103A infusion.

• Presence of RCL in peripheral blood.

  Up to 2 years after CT103A infusion.

Study Arms (1)

CT103A in patients with RRMM

EXPERIMENTAL

After lymphodepletion, CT103A will be administered as a single infusion.

Drug: Fully human BCMA chimeric antigen receptor autologous T cell injection (CT103A)

Interventions

Fully human BCMA chimeric antigen receptor autologous T cell injection (CT103A) DRUG

CT103A is an BCMA targeted genetically modified autologous T cell immunotherapy product that identifies and eliminates BCMA-expressing malignant and normal cells. CAR specifically recognizes BCMA with a low-immunogenic fully human single chain fragment variable (scFv), promotes CAR-T activation, proliferation, cytokine secretion and target cell killing through the CD3ζ domain, and enhances CAR-T proliferation and persistence through co-stimulatory signaling via 4-1BB.

Also known as: CT103A

CT103A in patients with RRMM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age.
• Documented diagnosed with multiple myeloma according to the IMWG diagnostic criteria.
• Have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulator-based chemotherapy, and an anti-CD38 therapy (prior exposure can be from different monotherapy or combination regimens), or are refractory to both a proteasome inhibitor and an immunomodulatory agent (i.e., double refractory).
• Documented disease progression during or within 12 months of the most recent anti-myeloma treatment (except for subjects who received CAR-T as last-line therapy).
• For subjects with previous BCMA-targeted therapy, the best response should be at least PR, and positive BCMA expression on tumor cells by immunohistochemistry (IHC) or flow cytometry is required before enrollment.
• The presence of measurable lesion according to IMWG 2016 criteria at screening as determined by any of the following criteria:
• Serum M-protein level ≥1.0 g/dL or urine M protein level ≥ 200 mg/24 h; or
• Light chain multiple myeloma without measurable lesions in serum or urine: Involved serum free light chain ≥ 10 mg/dL and abnormal serum κ/λ free light chain ratio.
• ECOG score of 0 or 1 (refer to Appendix 2)
• Subjects must have appropriate organ function and meet all the following laboratory test results prior to enrollment:
• Hematology: Absolute neutrophil count (ANC) ≥ 1×109/L (supportive growth factor is permitted, but must be without supportive treatment within 7 days before the laboratory test); absolute lymphocyte count (ALC) ≥0.3×109/L; platelet count ≥50×109/L (must be without supportive blood transfusion within 7 days before the laboratory test); hemoglobin ≥80 g/L (without transfusion of red blood cells \[RBC\] within 7 days before the laboratory test; the use of recombinant human erythropoietin is permitted).
• Liver function: Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5×upper limit of normal (ULN); serum total bilirubin ≤ 1.5×ULN except with known Gilbert's syndrome who have serum bilirubin ≤ 3×ULN.
• Renal function: Creatinine clearance (CrCl) calculated using the Cockcroft-Gault formula ≥ 40 ml/min.
• Coagulation function: Fibrinogen ≥1.0 g/L; activated partial thromboplastin time ≤1.5× ULN, prothrombin time (PT) ≤1.5× ULN.
• Corrected serum calcium ≤11 mg/dL

You may not qualify if:

• Subjects with graft versus host disease (GVHD) or those requiring long-term use of immunosuppressants.
• Received autologous hematopoietic stem cell transplant (Auto-HSCT) within 12 weeks before apheresis or received prior allogeneic hematopoietic stem cell transplant (Allo-HSCT).
• Received prior anti-myeloma therapies as follows:
• Treatment with monoclonal antibodies within 21 days prior to apheresis, or
• Treatment with cytotoxic chemotherapy or proteasome inhibitor within 14 days prior to apheresis, or
• Treatment with immunomodulator within 7 days prior to apheresis, or
• Anti-myeloma therapies other than those described above within 14 days or at least 5 half-lives (whichever is shorter) prior to apheresis.
• Use of glucocorticoids (defined as prednisone or equivalent \> 20 mg/day) at a therapeutic dose within 7 days prior to apheresis. Physiologic replacement, topical, and inhalation steroids are permitted, nevertheless.
• Severe heart disease: Including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive cardiac failure (New York Heart Association \[NYHA\] classification grade ≥ III), severe arrhythmia.
• Unstable systemic diseases judged by the investigator: Including but not limited to severe liver, kidney or metabolic diseases requiring therapy.
• Malignancies other than multiple myeloma within 5 years prior to screening, excluding adequately treated carcinoma in situ of cervix, basal or squamous epithelial cell skin cancer, localized prostate cancer post radical operation, ductal carcinoma in situ of the breast post radical operation.
• History of organ transplant.
• Suspected or confirmed central nervous system involvement.
• Plasma cell leukemia at the time of screening (\>2.0×109/L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary AL amyloidosis.
• Major surgery within 2 weeks prior to apheresis, or planned surgery within 2 weeks after study treatment administration (subjects who plan to receive surgery under local anesthesia are permitted to be enrolled in this study).

Sponsors & Collaborators

• Nanjing IASO Biotechnology Co., Ltd.: lead

Study Sites (1)

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Keam SJ. Equecabtagene Autoleucel: First Approval. Mol Diagn Ther. 2023 Nov;27(6):781-787. doi: 10.1007/s40291-023-00673-y. Epub 2023 Sep 2.

  PMID: 37658205 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

CT103A chimeric antigen receptor

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Nanjing IASO Biotherapeutics Co.,Ltd. Clinical trial

  Nanjing IASO Biotechnology Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Robert Z. Orlowski, M.D., Ph.D.

CONTACT

713-792-2860; rorlowsk@mdanderson.org

Oliver Kong, M.D.

CONTACT

+86 13162113618; Oliver.kong@iasobio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2022
• First Posted: January 26, 2023
• Study Start: May 8, 2023
• Primary Completion: May 20, 2024
• Study Completion: January 15, 2026
• Last Updated: January 26, 2023

Record last verified: 2022-12

Locations

US (1)