Roche announced that in a phase II study, IMvigor210, Tecentriq (atezolizumab) shrank tumours (objective response rate, ORR) in 24 per cent (n=28) of people with locally advanced or metastatic urothelial carcinoma (mUC) who have not received a prior treatment (first-line) and who were ineligible for cisplatin-based chemotherapy. Of those people who responded, 75 per cent (n=21) continued to respond to treatment and the median duration of response (mDOR) had not been reached at the time of analysis. Seven percent (n=8) of all people in the study achieved a complete response (CR). The median overall survival (OS) was 14.8 months.

The safety profile of Tecentriq was consistent with that observed in earlier analyses of the study, as well as in other studies of Tecentriq as a monotherapy. Full results presented in an oral session at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) and highlighted as part of ASCO’s official press programme.

“These Tecentriq results are highly encouraging because about half of all people with this type of bladder cancer are not able to tolerate a cisplatin-based chemotherapy, and alternative treatments bring very limited duration of response,” said Sandra Horning, M.D., chief medical officer and head of global product development. “We are particularly pleased that the majority of people who responded to Tecentriq continued to respond at the time of analysis.”

IMvigor210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of Tecentriq in people with locally advanced or mUC, 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 mUC and who were ineligible for first-line cisplatin-based chemotherapy. Cohort 2 included people whose disease progressed during or following previous treatment with a platinum-based chemotherapy regimen (second-line or later). 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 (programmed death-ligand 1) expression was assessed using an immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics.

Updated data from IMvigor 210 Cohort 1 (previously untreated, first-line) showed: ORR was 24 per cent (n=28) (95 per cent CI; 16, 32);  7 per cent (n=8) of all people in the study cohort achieved a complete response (CR);  Median DOR was not reached with a median follow-up duration of 14.4 months; 75 per cent of responses (n=21) were ongoing at the time of analysis;  Median OS was 14.8 months (95 per cent CI; 10.1, not estimable), and the 12 month landmark OS was 57 per cent.

Fifteen per cent of people receiving Tecentriq experienced severe (Grade 3 and 4) treatment-related adverse events. Six percent of people experienced an adverse event leading to treatment discontinuation, and 35 per cent had an adverse event leading to dose interruption. Six per cent of people experienced an adverse event leading to treatment discontinuation, and 35 per cent had an adverse event leading to dose interruption. Treatment-related adverse events (all grades) occurred in 66 per cent of people. One Grade 5 treatment-related adverse event occurred (sepsis, or blood infection). Six per cent of people had Grade 3-4 immune-mediated adverse events.

Updated results from IMvigor 210 Cohort 2, the trial upon which Tecentriq received US Food and Drug Administration accelerated approval for the treatment of people with locally advanced or mUC who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant), will be presented by Robert Dreicer, Associate Director of Clinical Research, Hematology and Oncology, University of Virginia School of Medicine, Charlottesville, Va. in an oral session (Abstract #4515, Sunday, June 5, 8:36 – 8:48 A.M. CDT).

Updated data from IMvigor 210 Cohort 2 (previously treated with platinum-based chemotherapy) showed:  An ORR of 16 per cent (n=49) (95 per cent CI; 12, 20);  7 per cent (n=21) of people achieved a CR;  Median DOR was not reached with a median follow-up duration of 17.5 months; 71 per cent of responses were ongoing at the time of analysis;  Median OS was 7.9 months (95 per cent CI, 7, 9), and he 12 month landmark OS was 37 per cent.

Seventeen percent of people receiving Tecentriq experienced severe (Grade 3 and 4) treatment-related adverse events. Three percent of people experienced an adverse event leading to treatment discontinuation, and 31 per cent had an adverse event leading to dose interruption. Treatment-related adverse events (all grades) occurred in 70 per cent of people. Three Grade 5 adverse events occurred: intestinal obstruction, sepsis (blood infection) and bleeding in the brain (cerebral hemorrhage)..

Tecentriq is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, Tecentriq may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.