Phase 2 study of MOXR0916 and Atezolizumab for bladder cancer

  • Research type

    Research Study

  • Full title

    A PHASE II, MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDY OF MOXR0916 IN COMBINATION WITH ATEZOLIZUMAB VERSUS ATEZOLIZUMAB ALONE IN PATIENTS WITH UNTREATED LOCALLY ADVANCED OR METASTATIC UROTHELIAL CARCINOMA WHO ARE INELIGIBLE FOR CISPLATIN-BASED THERAPY

  • IRAS ID

    221514

  • Contact name

    Thomas Powles

  • Contact email

    Thomas.Powles@bartsandthelondon.nhs.uk

  • Sponsor organisation

    Genentech, Inc

  • Eudract number

    2016-004165-58

  • Duration of Study in the UK

    5 years, 1 months, 24 days

  • Research summary

    Urothelial carcinoma (UC) is the most common type of bladder cancer. While bladder is most common location, UC may also originate in other parts of the urinary tract.
    Metastatic UC has an overall 5-year survival rate of 5.2%. Approximately half of the patients with locally advanced UC progress to metastatic disease within 2 years of bladder removal. The current treatments for metastatic UC are highly toxic and not suitable for many patients. Therefore, new less toxic treatments are needed.
    Atezolizumab is a new well tolerated immunotherapy drug with proven antitumour activity that is being investigated as a treatment for a wide variety of cancers. PD-L1 is a protein that dampens immune responses through binding to its receptors. Atezolizumab targets PD-L1 and inhibits the interaction between PD-L1 and its receptors. This blockage results in improvement of the tumour-specific immune response.
    MOXR0916 is an experimental immunotherapy drug that activates the OX40 pathway and is designed to increase the ability of the immune system's T-cells to fight cancer more effectively.
    Combining MOXR0916 and Atezolizumab may increase the immune system’s antitumour response more than each drug alone.
    This study will evaluate the efficacy, as measured by progression free survival and overall survival, and safety of MOXRO916 plus Atezolizumab compared with placebo plus Atezolizumab in patients with locally advanced or metastatic UC who have not received prior systemic therapy and who are ineligible to receive cisplatin-based therapy.
    Up to 225 patients will be enrolled at approximately 75 sites globally, of which 4 sites will be in the UK. Enrolment will occur in two stages. In Stage 1, approximately 160 patients will be enrolled irrespective of the tumour PD-L1 score. In Stage 2, enrolment will be limited to patients with a tumour PD-L1 score of IC2/3 who may respond to Atezolizumab better. Enrolment will continue until approximately 80 total IC2/3 patients have been recruited across both stages.
    Upon successful screening, patients will enter the treatment phase where they will receive Atezolizumab and MOXR0916 or placebo infusions every 3 weeks. Treatment will continue until disease progression, development of intolerable toxicity or other threat to patient’s safety, pregnancy in females, start of other anti-cancer therapy. Patients will return for a Treatment Discontinuation visit within 30 days of receiving the last dose of the drugs after which they will be followed for disease progression and survival every 6-12 weeks.
    Assessments for this study include physical examinations, vital signs, pulse oximetry, ECG, blood and urine tests, optional and mandatory tumour biopsies, CT, MRI or PET/CT scans, quality of life questionnaires.
    The study is expected to last 45 months.

  • REC name

    East of England - Essex Research Ethics Committee

  • REC reference

    17/EE/0022

  • Date of REC Opinion

    14 Feb 2017

  • REC opinion

    Further Information Favourable Opinion