Early results from a pivotal phase II study, IMvigor 210, of the investigational cancer immunotherapy Atezolizumab ( anti-PDL1; MPDL3280A ) in people with locally advanced or metastatic urothelial carcinoma ( mUC ) have shown that Atezolizumab shrank tumours ( objective response rate, ORR ) in 27% of people with metastatic urothelial carcinoma 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.
IMvigor 210 is an open-label, multicentre, single-arm phase II study that has evaluated the safety and efficacy of Atezolizumab in people with locally advanced or metastatic urothelial carcinoma, 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 urothelial carcinoma, but who were ineligible for first-line Cisplatin-based therapy; results for this cohort are not yet mature.
Cohort 2 included people whose disease had progressed during or following previous treatment with a Platinum-based chemotherapy regimen.
People received a 1200-mg 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.
People were selected by histology, prior lines of therapy and PD-L1 expression on tumour-infiltrating immune cells ( IC ), using an investigational immunohistochemistry ( IHC ) test that is being developed by Roche Diagnostics.
In addition to IMvigor 210, Roche has an ongoing randomised phase III study, IMvigor 211, comparing Atezolizumab with standard-of-care chemotherapy in people who have metastatic urothelial carcinoma that worsened after initial treatment.
All studies include the evaluation of a companion test developed by Roche Diagnostics to determine PD-L1 status.
Metastatic urothelial cancer is associated with a poor prognosis and limited treatment options. It is a disease that has seen no major advancements for nearly 30 years. Urothelial cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 145,000 deaths globally each year. Men are three times more likely to suffer from urothelial cancer compared with women, and it is also three times more common in developed countries than in less developed countries.
Atezolizumab is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, Atezolizumab may enable the activation of T cells.
All studies of Atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both tumour cells and tumour-infiltrating immune cells.
The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with Atezolizumab alone, and to determine which people may benefit most from a combination of Atezolizumab and another medicine.
There are 11 ongoing or planned phase III studies of Atezolizumab across certain kinds of lung, kidney, breast and bladder cancer. ( Xagena )
Source: Roche, 2015