A phase I/Ib study of BTCT4465A

  • Research type

    Research Study

  • Full title

    AN OPEN-LABEL, MULTICENTER, PHASE I/IB TRIAL EVALUATING THE SAFETY AND PHARMACOKINETICS OF ESCALATING DOSES OF BTCT4465A AS A SINGLE AGENT AND COMBINED WITH ATEZOLIZUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN’S LYMPHOMA AND CHRONIC LYMPHOCYTIC LEUKEMIA.

  • IRAS ID

    241654

  • Contact name

    Sunil Iyengar

  • Contact email

    Sunil.Iyengar@rmh.nhs.uk

  • Sponsor organisation

    Genentech, Inc

  • Eudract number

    2017-003267-35

  • Clinicaltrials.gov Identifier

    NCT02500407

  • Duration of Study in the UK

    0 years, 7 months, 25 days

  • Research summary

    Diffuse large B-cell lymphoma is a common type of non-Hodgkin lymphoma (NHL). It develops when the body makes abnormal B-cells (white blood cells that fight infection).

    Chronic lymphocytic leukaemia is a type of slow growing leukaemia that affects developing B-cells causing a cancerous change and become leukaemic cells.

    Patients with advanced stage B-cell malignancies are typically initially target the toxic cells with intensive chemotherapy and with cloning antibodies to help fight the disease. Although positive responses can be achieved in some patients, the majority of patients will ultimately experience progressive or relapsed disease. NHL is most often diagnosed in older patients who struggle with the continuous cytotoxic chemotherapy. Consequently, there remains a need for treatments that can significantly extend disease-free survival and overall survival, while providing at least acceptable if not superior safety and tolerability.

    Recent developments have supported the effectiveness of therapies that utilize T cells in the treatment of B-cell cancers. This study hopes to utilise BTCT4465A which targets B-cells and kills cancer cells when binding to both CD20 on B cells and CD3 on T cells. Both of these provide the optimal B-cell immune response, specifically against T-independent antigens resulting in T-cell activation in a target- and dose-dependent manner.

    Atezolizumab is an antibody that is shown to have anti-tumour properties. It targets PD-L1 and inhibits the interaction between PD-L1 and its receptors. This blockage results in improvement of the tumour-specific T-cell responses creating an increase in anti-tumour activity.

    The goals of this Phase I/Ib study are to assess the safety, tolerability, pharmacokinetics, and potential biologic and clinical activity of escalating doses of BTCT4465A, as a single agent and in combination with atezolizumab, in patients with cancer that begin in the cells of blood-forming tissue on the cells of the immune system. This is to help to determine a recommended Phase II dose and schedule of BTCT4465A as a single agent and in combination with atezolizumab.
    The study will enroll approximately 160 patients during the dose-escalation stage (100-120 NHL patients and 20-40 CLL patients) and approximately 290-510 patients during the expansion stage at approximately 35-45 investigative sites globally. The planned duration of the study is approximately 4 years.

  • REC name

    South Central - Berkshire B Research Ethics Committee

  • REC reference

    18/SC/0680

  • Date of REC Opinion

    22 Dec 2018

  • REC opinion

    Favourable Opinion