US FDA grants Breakthrough Therapy Designation for combination immunotherapy in HCC treatment


Roche has announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as first-line treatment for people with advanced or metastatic hepatocellular carcinoma (HCC). The designation is based on data from a phase Ib study assessing the safety and clinical activity of the combination of Tecentriq and Avastin.

Sandra Horning, Roche’s chief medical officer and head of Global Product Development said: “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, a press release from the company states.

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%) of 23 efficacy-evaluable patients. Responses were seen in all subgroups, including on the basis of the cause of their disease (aetiology: Hepatitis B, Hepatitis C, and non-viral), region (Asia excluding 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% (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% 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.

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 (1200mg) 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).


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