Tuesday, Jul 17, 2018

FDA Grants Breakthrough Therapy Designation for Genentech’s TECENTRIQ in Combination With Avastin as First-Line Treatment for Advanced or Metastatic Hepatocellular Carcinoma (HCC)

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. 

• TECENTRIQ may be used when your bladder cancer:
  • has spread or cannot be removed by surgery, and if you have any one of the following conditions:
  • you are not able to take chemotherapy that contains a medicine called cisplatin, and your doctor has tested your cancer and found high levels of a specific protein on your cancer called programmed death-ligand 1 (PD-L1), or
  • you are not able to take chemotherapy that contains any platinum regardless of PD-L1 status on your cancer, or
  • you have tried chemotherapy that contains platinum, and it did not work or is no longer working

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). 

• TECENTRIQ may be used when your lung cancer:
  • has spread or grown, and
  • you have tried chemotherapy that contains platinum, and it did not work or is no longer working

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: 

• Lung problems (pneumonitis) –signs and symptoms may include new or worsening cough, shortness of breath, and chest pain
• Liver problems (hepatitis) –signs and symptoms of hepatitis may include yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
• Intestinal problems (colitis) –signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucous in the stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
•  Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary)  –signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
• Problems in other organs –signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
• Severe infections –signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
• Severe infusion reactions –signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of the face or lips, dizziness, fever, feeling like passing out, and back or neck pain

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: 

• have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
• are pregnant or plan to become pregnant. TECENTRIQ can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with TECENTRIQ. If patients are able to become pregnant:
  • A healthcare provider should do a pregnancy test before they start treatment with TECENTRIQ.
  • They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of TECENTRIQ.
• are breastfeeding or plan to breastfeed. It is not known if TECENTRIQ passes into the breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of TECENTRIQ

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: 

• feeling tired
• decreased appetite
• nausea
• constipation
• urinary tract infection
• diarrhea
• fever

The most common side effects of TECENTRIQ in people with non-small cell lung cancer include: 

• feeling tired
• decreased appetite
• muscle pain
• cough
• shortness of breath

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 Indications: 

• Metastatic colorectal cancer (mCRC) for first- or second-line treatment in combination with intravenous 5-fluorouracil–based chemotherapy. It is also approved to treat mCRC for second-line treatment, when used with fluoropyrimidine-based (combined with irinotecan or oxaliplatin) chemotherapy, after cancer progresses following a first-line treatment that includes Avastin.
  • Avastin is not approved for use after the primary treatment of colon cancer that has not spread to other parts of the body
•  Advanced nonsquamous non–small cell lung cancer (NSCLC)  in combination with carboplatin and paclitaxel, in people who have not received chemotherapy for their advanced disease
• Metastatic kidney cancer (mRCC) when used with interferon alfa
• Glioblastoma (GBM) in adult patients whose cancer has progressed after prior treatment (recurrent or rGBM)
• Advanced cervical cancer (CC) in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is approved to treat persistent, recurrent, or metastatic cancer of the cervix
• Ovarian cancer (OC).  Avastin, in combination with carboplatin and paclitaxel, followed by Avastin alone, is used for the treatment of patients with advanced (Stage III or IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgery.

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):

• GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
• Wounds that don’t heal. A cut made during surgery can be slow to heal or may not fully heal. Avastin should not be used for at least 28 days before or after surgery and until surgical wounds are fully healed
• Serious bleeding. This includes vomiting or coughing up blood; bleeding in the stomach, brain, or spinal cord; nosebleeds; and vaginal bleeding. If a patient has recently coughed up blood or had serious bleeding, they should be sure to tell their doctor

Other possible serious side effects

• Abnormal passage in the body. This type of passage—known as a fistula—is an irregular connection from one part of the body to another and can sometimes be fatal
• Severe high blood pressure. Blood pressure that severely spikes or shows signs of affecting the brain. Blood pressure should be monitored every 2 to 3 weeks while on Avastin and after stopping treatment
• Kidney problems. These may be caused by too much protein in the urine and can sometimes be fatal
• Infusion reactions. These were uncommon with the first dose (less than 3% of patients). 0.2% of patients had severe reactions. Infusion reactions include high blood pressure or severe high blood pressure that may lead to stroke, trouble breathing, decreased oxygen in red blood cells, a serious allergic reaction, chest pain, headache, tremors, and excessive sweating. The patient’s doctor or nurse will monitor for signs of infusion reactions
• Severe stroke or heart problems. These may include blood clots, mini-stroke, heart attack, chest pain, and the heart may become too weak to pump blood to other parts of the body (congestive heart failure). These can sometimes be fatal
• Nervous system and vision problems. Signs include headache, seizure, high blood pressure, sluggishness, confusion, and blindness

Side effects seen most often

In clinical studies across different types of cancer, some patients experienced the following side effects:

• High blood pressure
• Too much protein in the urine
• Nosebleeds
• Rectal bleeding
• Back pain
• Headache
• Taste change
• Dry skin
• Inflammation of the skin
• Inflammation of the nose
• Watery eyes

Avastin is not for everyone

Patients should talk to their doctor if they are:

• Undergoing surgery. Avastin should not be used for 28 days before or after surgery and until surgical wounds are fully healed
• Pregnant or think they are pregnant. Data have shown that Avastin may harm a woman’s unborn baby. Birth control should be used while patients are on Avastin. If Avastin is stopped, patients should keep using birth control for 6 months before trying to become pregnant
• Planning to become pregnant. Taking Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children
• Breastfeeding. Breastfeeding while on Avastin may harm the baby and is therefore not recommended during and for 6 months after taking Avastin

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.

About Genentech

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.

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