Regulatory Decision Summary for Tecentriq

Authorization of Tecentriq, in combination with bevacizumab, was based on results from an open-label controlled Phase III trial of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who required systemic therapy. At total of 501 patients were randomized 2:1 to receive first-line treatment with the combination of Tecentriq plus bevacizumab (n = 336) or the current standard of care, sorafenib (n = 165). The primary efficacy endpoints were overall survival (OS) and progression-free survival (PFS). A key secondary endpoint was confirmed objective response rates by independent review facility (IRF) assessments.

A statistically significant and clinically meaningful improvement in OS and PFS was reported for Tecentriq plus bevacizumab over sorafenib. The observed OS and PFS hazard ratios translated into a 42% reduction in the risk of death and 41% reduction in the risk of disease progression or death, respectively, in the Tecentriq plus bevacizumab arm compared with the sorafenib arm. The median OS was not reached in the Tecentriq plus bevacizumab arm and was 13.2 months in the sorafenib arm. The median PFS was 6.8 months (95% CI: 5.8, 8.3) in the Tecentriq plus bevacizumab arm and 4.3 months in the sorafenib arm (95% CI: 4.0, 5.6). Patients in the Tecentriq plus bevacizumab arm also had more confirmed IRF objective response rates compared to patients treated with sorafenib (27% vs. 12%).

The safety of Tecentriq plus bevacizumab is consistent with the known safety profiles of the two monoclonal antibodies. Bleeding (including fatal events) is a known adverse reaction with bevacizumab and upper gastrointestinal bleeding is a common and life threatening complication in patients with HCC. Hence, HCC patients were required to be evaluated for the presence of varices within 6 months prior to treatment and were excluded from the Phase III trial if they had variceal bleeding, untreated or incompletely treated varices with bleeding or varices with a high risk of bleeding. Therefore, there is lack of clinical data to support the combination of Tecentriq and bevacizumab for patients who were excluded due to bleeding varices or untreated or incompletely treated varices. Information regarding the lack of clinical data to support the combination therapy in these patients for the HCC indication is included in the Tecentriq Product Monograph.

The recommended dose of Tecentriq is 1,200 mg administered as an intravenous infusion over 60 minutes, followed by 15 mg/kg of bevacizumab, every 3 weeks until loss of clinical benefit or unacceptable toxicity.

A Notice of Compliance (NOC) was recommended.