Clinical Trials

Date: 2015-09-27

Type of information: Results

phase: 2

Announcement: results

Company: Roche (Switzerland)

Product: atezolizumab (MPDL3280A)

Action mechanism: immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. Anti-PDL1 antibody atezolizumab (MPDL3280A) is an investigational medicine designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. MPDL3280A is being studied in clinical trials to understand whether blocking PD-L1 will help the immune system respond to cancer. MPDL3280A is being studied in clinical trials alone and with other medicines that directly interfere with how cancer grows and spreads. The FDA granted Breakthrough Therapy Designation for atezolizumab in people whose metastatic bladder cancer expressed PD-L1.

Disease: locally advanced or metastatic urothelial bladder cancer (UBC) that had progressed on initial treatment

Therapeutic area: Cancer - Oncology

Country: Canada, France, Germany, Italy, Netherlands, Spain, UK, USA

Trial details: IMvigor 210 is an open-label, multicenter, single-arm Phase II study that evaluated the safety and efficacy of atezolizumab in people with locally advanced or metastatic UBC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1 consisted of people who had received no prior therapies for locally advanced or metastatic UBC, but who were ineligible for first-line cisplatin-based therapy; results from this cohort are not yet mature. Cohort 2, for which results were announced today, included people whose disease progressed during or following previous treatment with a platinum-based chemotherapy regimen (second-line or later). People received a 1200-milligram intravenous dose of atezolizumab on day one of 21-day cycles until progressive disease (Cohort 1) or loss of clinical benefit (Cohort 2). The primary endpoint of the study was ORR. Secondary endpoints included duration of response (DoR), overall survival (OS), progression-free survival (PFS) and safety. PD-L1 expression was assessed using an investigational immunohistochemistry (IHC) test being developed by Roche Diagnostics. (NCT02108652)

Latest news:

• • On September 27 2015, Roche announced early results from the phase II study, IMvigor 210, of  atezolizumab (anti-PDL1; MPDL3280A) in people with locally advanced or metastatic urothelial carcinoma (mUC). The study showed that atezolizumab shrank tumours  in 27 percent of people with mUC whose disease had medium and high levels of PD-L1 expression and worsened after initial treatment. Ninety-two percent of people who responded to atezolizumab continued to respond when the results were assessed. Median duration of response was not yet reached. Adverse events were consistent with those observed in previous studies. Roche is planning to submit these data to global health authorities and to the FDA under a Breakthrough Therapy Designation for the treatment of people whose metastatic bladder cancer expresses PD-L1. This designation is designed to expedite the development and review of medicines intended to treat serious diseases that may demonstrate substantial improvement over existing therapies.
• • On July 13, 2015, Roche announced that in the IMvigor 210 study, atezolizumab shrank tumours in people with locally advanced or metastatic urothelial bladder cancer (UBC) who had progressed on initial treatment (second-line or later). High amounts of PD-L1 (Programmed Death Ligand-1) expression by a person’s cancer correlated with increased response to the medicine. Adverse events were consistent with what has been previously observed for atezolizumab. In addition to the IMvigor 210 study, Roche has an ongoing randomised Phase III study, IMvigor 211, comparing atezolizumab with standard-of-care chemotherapy in people who have relapsed UBC, and a planned Phase III study, IMvigor 010, that will evaluate atezolizumab compared with observation in people with early-stage muscle-invasive bladder cancer who are selected for PD-L1 expression and are at risk for recurrence (adjuvant). All studies include the evaluation of a companion test developed by Roche Diagnostics to determine PD-L1 status.This phase II, single-arm study was designed to evaluate the effect of Atezolizumab treatment in patients with locally advanced or metastatic urothelial bladder cancer. Patients will be enrolled into 1 of 2 cohorts. Cohort 1 will consist of patients who are treatment-naïve and ineligible for platinum-containing therapy. Cohort 2 will contain patients who have progressed during or following a prior platinum-based chemotherapy regimen. Patients in both cohorts will be given a 1200 mg intravenous (IV) dose of atezolizumab on Day 1 of 21-day cycles. Treatment of patients in Cohort 1 will continue until disease progression per RECIST v1.1 criteria or unmanageable toxicity. Treatment of patients in Cohort 2 will continue until loss of clinical benefit or unmanageable toxicity. Patients will be followed for up for 2 years.

Is general: Yes