Roche has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab) as an initial (first-line) treatment for people with advanced or metastatic hepatocellular carcinoma (HCC), the most common form of liver cancer. The designation is based on data from a Phase Ib study assessing the safety and clinical activity of the combination of Tecentriq and Avastin.
“Hepatocellular carcinoma is an aggressive cancer with limited treatment options and a major cause of cancer deaths worldwide,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Preliminary data from the combination of Tecentriq and Avastin in this disease are promising and we look forward to working with health authorities to make this potential treatment regimen available to people with hepatocellular carcinoma as soon as possible.”
Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. This is the 22nd Breakthrough Therapy Designation for Roche’s portfolio of medicines and the 3rd for Tecentriq.
Roche presented data from a Phase Ib study in HCC at the American Society of Clinical Oncology (ASCO) Annual Meeting, in June 2018. These data showed that after a median follow-up of 10.3 months, responses (independent review facility (IRF) per RECIST v1.1) were seen in 15 (65 percent) of 23 efficacy-evaluable patients. Responses were seen in all subgroups, including on the basis of the cause of their disease (etiology: Hepatitis B, Hepatitis C, and non-viral), region (Asia excl. Japan or Japan/US), baseline alpha-fetoprotein levels (high/low) or spread of tumour beyond the liver (yes/no). Assessment by investigators (INV) assessed per RECIST v1.1 demonstrated a response rate of 61 percent (14 out of 23 patients). Median progression free survival (PFS), duration of response (DOR), time to progression (TTP) and overall survival (OS) have not yet been reached after a median follow-up of 10.3 months; results will be presented at a future medical congress when updated data from an expanded cohort are available. In the safety-evaluable population (n=43), 28 percent of patients (n=12) experienced Grade 3-4 treatment-related adverse events and no treatment-related Grade 5 adverse events were observed. No new safety signals were identified beyond the established safety profiles for the individual medicines. Roche provided additional data per FDA request and the Breakthrough Therapy Designation has been granted based on the totality of these data.
Earlier this year, Roche initiated IMbrave150 (NCT03434379), an open-label, multicentre, randomised Phase III study investigating the combination of Tecentriq and Avastin versus sorafenib in people with previously-untreated (first-line) locally advanced, unresectable or metastatic HCC. This study is currently enrolling. Further information about the trial can be found on clinicaltrials.gov.
About the Phase Ib study (NCT02715531)
This Phase Ib, open-label, multicentre study is evaluating the safety and clinical activity of a number of cancer immunotherapy combinations in different solid tumours, including Tecentriq and Avastin in patients with advanced, unresectable or metastatic first-line HCC (Arm A). Participants in Arm A receive Tecentriq (1200 mg) and Avastin (15 mg/kg) intravenously (IV) every three weeks until loss of clinical benefit or unacceptable toxicity. The primary objectives of Arm A are to assess the clinical activity, based on objective response rate (ORR) assessment by independent review facility (IRF) per RECIST v1.1 and to assess the safety and tolerability of the combination. Secondary efficacy endpoints include objective response rate (ORR) by investigator assessment (INV), as well as progression-free survival (PFS), duration of response (DOR), time to progression (TTP) all by INV and IRF per RECIST v1.1; and overall survival (OS).
About Hepatocellular Carcinoma (HCC)
Liver cancer is the second most common cause of cancer death globally1 and HCC is the most common primary malignancy of the liver. Globally, HCC is the fifth most common cancer in men and the seventh most common cancer among women, with over half a million new cases diagnosed annually1. HCC develops predominantly in those people with cirrhosis due to chronic hepatitis B or C2.