Tuesday, Jul 17, 2018
South San Francisco, CA -- July 17, 2018 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today 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, M.D., 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 Genentech’s portfolio of medicines and the 3rd for TECENTRIQ.
Genentech 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 participants. 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 [excluding Japan] or Japan/U.S.), baseline alpha-fetoprotein levels (high/low) or spread of tumor 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 participants). 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 participants (n=12) experienced Grade 3-4 treatment-related adverse events (AEs), and no treatment-related Grade 5 AEs were observed. No new safety signals were identified beyond the established safety profiles for the individual medicines. Genentech provided additional data per FDA request and the Breakthrough Therapy Designation has been granted based on the totality of these data.
Earlier this year, Genentech initiated IMbrave150 (NCT03434379), an open-label, multicenter, randomized 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, multicenter study is evaluating the safety and clinical activity of a number of cancer immunotherapy combinations in different solid tumors, including TECENTRIQ and Avastin in people 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 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 IMbrave150 (NCT03434379)
IMbrave150 is a Phase III, multicenter, randomized, open-label study enrolling approximately 480 people with untreated advanced, unresectable or metastatic HCC 2:1 to receive the combination of TECENTRIQ and Avastin or sorafenib. TECENTRIQ will be administered IV, 1200 mg on day 1 of each 21-day cycle and Avastin will be administered IV, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib will be administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle. Participants will receive the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints are OS and investigator-assessed ORR. Secondary endpoints include investigator-assessed PFS, TTP, DoR and IRF-assessed ORR, PFS, TTP and DoR.
About Hepatocellular Carcinoma (HCC)
HCC accounts for approximately 75 percent of all liver cancer cases diagnosed in the United States, with more than 20,000 men and more than 5,000 women diagnosed annually. HCC develops predominantly in people with cirrhosis due to chronic hepatitis B or C, and typically presents at an advanced stage where there are limited treatment options.
About the TECENTRIQ® (atezolizumab) and Avastin® (bevacizumab) combination
There is a strong scientific rationale to support the use of TECENTRIQ plus Avastin in combination. The TECENTRIQ and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance TECENTRIQ’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumor infiltration and enabling priming and activation of T-cell responses against tumor antigens.
About TECENTRIQ® (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1. TECENTRIQ is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the re-activation of T cells. TECENTRIQ may also affect normal cells.
About Avastin® (bevacizumab)
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize).
TECENTRIQ U.S. Indication (pronounced ‘tē-SEN-trik’)
TECENTRIQ is a prescription medicine used to treat:
A type of bladder and urinary tract cancer called urothelial carcinoma.
The approval of TECENTRIQ in these patients is based on a study that measured response rate and duration of response. There is an ongoing study to confirm clinical benefit.
A type of lung cancer called non-small cell lung cancer (NSCLC).
If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.
It is not known if TECENTRIQ is safe and effective in children.
Important Safety Information
What is the most important information about TECENTRIQ?
TECENTRIQ can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.
Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.
TECENTRIQ can cause serious side effects, including:
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with TECENTRIQ if patients have severe side effects.
Before receiving TECENTRIQ, patients should tell their healthcare provider about all of their medical conditions, including if they:
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
The most common side effects of TECENTRIQ in people with urothelial carcinoma include:
The most common side effects of TECENTRIQ in people with non-small cell lung cancer include:
TECENTRIQ may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.
These are not all the possible side effects of TECENTRIQ. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.
Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.
Please visit http://www.Tecentriq.com for the TECENTRIQ full Prescribing Information for additional Important Safety Information.
Avastin in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan, is approved to treat platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer (prOC) in women who received no more than two prior chemotherapy treatments.
Avastin, either in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine, followed by Avastin alone, is approved for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (psOC)
Possible serious side effects
Everyone reacts differently to Avastin therapy. So, it’s important to know what the side effects are. Although some people may have a life-threatening side effect, most do not. Their doctor will stop treatment if any serious side effects occur. Patients should contact their health care team if there are any signs of these side effects.
Most serious side effects (not common, but sometimes fatal):
Other possible serious side effects
Side effects seen most often
In clinical studies across different types of cancer, some patients experienced the following side effects:
Avastin is not for everyone
Patients should talk to their doctor if they are:
Patients should talk with their doctor if they have any questions about their condition or treatment.
Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.
For full Prescribing Information and Boxed WARNINGS on Avastin please visit http://www.avastin.com.
About Genentech in Personalized Cancer Immunotherapy
For more than 30 years, Genentech has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer. The goal of PCI is to provide each person with a treatment tailored to harness his or her own immune system to fight cancer. Genentech is studying more than 20 investigational medicines, 10 of which are in clinical trials. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit http://www.gene.com/cancer-immunotherapy.
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.