Relapsed/refractory patients

CT103A for relapsed/refractory multiple myeloma

The National Medical Products Administration (NMPA) in China has granted approval to the investigational new drug (IND) application for CT103A, for the treatment of relapsed/refractory (R/R) multiple myeloma (MM).1

What is CT103A?

CT103A is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) which is found on the surface of myeloma plasma cells. It contains a fully-human BCMA antibody, designed to reduce the toxic side effects often induced by non-human constructs.2

CT103A uses a lentiviral vector containing a CAR construct with a fully human single-chain variable fragment (scFv), CD8a hinge and transmembrane, 4-1BB costimulatory- and CD3z activation- domains.1

Clinical trials

The pilot clinical study (ChiCTR1800018137) was an open-label, single-center and single-arm trial in patients aged 18–70 with R/R plasma cell malignancies.3 The study was conducted at the Tongji Hospital of Tongji Medical College, Wuhan, CH.4

During the XVII International Myeloma Workshop in Boston, US, the clinical responses and pharmacokinetics of CT103A were presented;4

  • Study objectives:
    • Primary: characterize the safety and tolerability of CT103A in patients with RRMM
    • Secondary: evaluation of anti-myeloma activity, cytokines, CAR T persistence and pharmacokinetics
  • Twelve patients were enrolled
    • Four had relapsed after murine BCMA CAR T therapy
    • Five had extramedullary disease and/or plasma cell leukemia
  • Median prior lines of therapy: 4 (3–6)
  • Conditioning: cyclophosphamide and fludarabine
  • Dosing: 3+3 dose escalation trial
    • Four doses of 1 x106/kg, 3 x106/kg or 6 x106/kg CT103A
  • Efficacy:
    • Overall response rate (ORR), as of June 18th 2019: 100%
    • Four patients achieved complete response (CR) within two weeks post-infusion (4/12)
    • Of 11 evaluable patients:
      • Stringent CR (sCR): 64%
        • Including three patients who participated in prior CAR T trials (3/4)
      • Very good partial response (VGPR): 36%
        • Including one patient who participated in a prior CAR T trial (1/4)
  • Pharmacokinetics:
    • Median Tmax: 14 days (9–25) post-infusion
    • Longest CT103A persistence: 260 days
  • Safety:
    • First two dose groups; cytokine release syndrome (CRS) occurred at grades 0–2
    • One grade four CRS occurred at 6 x106/kg and was considered a dose-limiting toxicity
    • No neurotoxicity observed across all dose groups

The authors of the study concluded CT103A could be a consolidative therapeutic agent for patients with RRMM based on the high ORR, quick response rate and lack of major adverse events.

The drug company responsible for the therapy are preparing for a phase Ib/II trial launch in China in patients with RRMM.2

Read more about CAR T in MM here.

References
  1. Business Wire. NMPA Approves IND Application for CT103A, a Fully-human BCMA CAR-T for the Treatment of Relapsed/Refractory Multiple Myeloma Co-developed by IASO BIO and Innovent Biologics. https://www.businesswire.com/news/home/20191002005214/en [Accessed 2019 Oct 10]
  2. Chinese Regulatory Agency Clears CT103A for Clinical Studies in Relapsed or Refractory Multiple Myeloma. https://myelomaresearchnews.com/2019/10/09/ct103a-cleared-clinical-studies-relapsed-refractory-mm-in-china/ [Accessed 2019 Oct 10]
  3. Chinese Clinical Trial Registry. An open-label, single-center and single-arm clinical study of infusion of anti-BCMA CAR-T cells for patients with relapsed or refractory plasma cell malignancies. http://www.chictr.org.cn/showprojen.aspx?proj=30653 [Accessed 2019 Oct 10] 
  4. Wang J. et al., Clinical Responses and Pharmacokinetics of fully-human BCMA targeting CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma. XVII International Myeloma Workshop (IMW). 2019 Sep 14. Abstract #OAB-033
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