Genentech’s Tecentriq Plus Avastin Reduced the Risk of Cancer Returning in People With Certain Types of Adjuvant Liver Cancer in a Phase III Study

– In the first-ever positive Phase III trial in the adjuvant hepatocellular carcinoma (HCC) setting, Tecentriq plus Avastin reduced the risk of disease recurrence by 28% –

– Up to 80% of people with this type of HCC experience disease recurrence, at which point they are faced with poorer prognosis and shorter survival –

– These data will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2023 and included in the official press program –

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today new data from the Phase III IMbrave050 study that show Tecentriq^® (atezolizumab) plus Avastin^® (bevacizumab) demonstrated a statistically significant improvement in recurrence-free survival (RFS) in people with hepatocellular carcinoma (HCC) at high risk of disease recurrence following liver resection or ablation with curative intent.

“Four out of five people with HCC who receive surgery with curative intent may still see their cancer return. Thus, an urgent need exists for adjuvant treatments to prevent early recurrence and improve survival rates,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “With Tecentriq plus Avastin already a standard of care in unresectable HCC, we are pleased with the potential of these results and look forward to seeing more mature data.”

The Tecentriq investigational combination reduced the risk of cancer returning by 28%, compared with active surveillance, at a median follow-up of 17.4 months (independent review facility [IRF]-RFS hazard ratio [HR]=0.72, 95% CI: 0.56-0.93; P=0.0120). The IRF-RFS findings were generally consistent across clinical subgroups. Overall survival (OS), a key secondary endpoint, was immature (7% event-rate) at the time of data analysis. The safety data for Tecentriq plus Avastin were consistent with the well-established safety profile of each therapeutic treatment and with the underlying disease.

The late-breaking data will be presented at the AACR Annual Meeting 2023 and have been included as part of the official press program. Discussions with health authorities are ongoing and follow-up will continue for the final RFS data and more mature OS data at the next planned analysis.

The IMbrave050 study is part of Genentech’s overall commitment to drive fundamental treatment change and improve outcomes for people living with liver cancer. Tecentriq plus Avastin was the first treatment in over a decade to significantly improve OS over the existing standard of care, based on data from the IMbrave150 study. The Tecentriq combination quickly became a standard of care in unresectable HCC and is clearly defined as a preferred front-line treatment in multiple international clinical guidelines.

Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across different lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumor types. In addition, Genentech has developed a subcutaneous formulation of Tecentriq, which is currently under review by health authorities globally.

About the IMbrave050 study

IMbrave050 is a Phase III global, multicenter, open-label, randomized study evaluating the efficacy and safety of adjuvant Tecentriq plus Avastin, compared with active surveillance, in people with HCC at high risk of recurrence (determined by the size and number of cancerous lesions and the histopathology results, if available) after surgical resection or ablation with curative intent.

The study randomized 668 people with a ratio of 1:1 to receive either Tecentriq (1,200 mg every three weeks) plus Avastin (15 mg/kg every three weeks) for a period of 12 months or 17 cycles, or no intervention with active surveillance. The primary endpoint is independent review facility-assessed RFS. Key secondary endpoints include OS, RFS as determined by the investigator and RFS in patients with PD-L1-positive disease.

About hepatocellular carcinoma

Liver cancer is the third leading cause of cancer death and one of the few cancers where mortality is rising. It is estimated that nearly 42,000 Americans were diagnosed with liver cancer in 2022. Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD) and cirrhosis resulting from these conditions.

If diagnosed in the early stage, surgery may be prescribed to remove the primary tumor, however an estimated 70-80% of people with early-stage HCC experience disease recurrence following surgery. Early recurrence is associated with poorer prognosis and shorter survival. Tumor size, number of tumors, and portal vein invasion are associated with an increased risk of recurrence.

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 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. Indications

Tecentriq is a prescription medicine used to treat:

Adults with a type of lung cancer called non-small cell lung cancer (NSCLC).

• Tecentriq may be used alone as a treatment for their lung cancer:
  • to help prevent their lung cancer from coming back after their tumor(s) has been removed by surgery and they have received platinum-based chemotherapy, and
  • they have stage 2 to 3A NSCLC (patients should talk to their healthcare provider about what these stages mean), and
  • their cancer tests positive for “PD-L1.”

• Tecentriq may be used alone as their first treatment when their lung cancer:
  • has spread or grown, and
  • their cancer tests positive for “high PD-L1,” and
  • their tumor does not have an abnormal “EGFR” or “ALK” gene.

• Tecentriq may be used with the medicines bevacizumab, paclitaxel, and carboplatin as their first treatment when their lung cancer:
  • has spread or grown, and
  • is a type called “non-squamous NSCLC,” and
  • their tumor does not have an abnormal “EGFR” or “ALK” gene.

• Tecentriq may be used with the medicines paclitaxel protein-bound and carboplatin as their first treatment when their lung cancer:
  • has spread or grown, and
  • is a type called “non-squamous NSCLC,” and
  • their tumor does not have an abnormal “EGFR” or “ALK” gene.

• Tecentriq may be used alone when their lung cancer:
  • has spread or grown, and
  • if they have tried chemotherapy that contains platinum, and it did not work or is no longer working.
  • if their tumor has an abnormal “EGFR” or “ALK” gene, they should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

Adults with a type of lung cancer called small cell lung cancer (SCLC). Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as their first treatment when their lung cancer:

• is a type called “extensive-stage small cell lung cancer,” which means that it has spread or grown.

Adults with a type of liver cancer called hepatocellular carcinoma (HCC). Tecentriq may be used with the medicine bevacizumab when their liver cancer:

• has spread or cannot be removed by surgery, and
• they have not received other medicines by mouth or injection through their vein (IV) to treat their cancer.

Adults with a type of skin cancer called melanoma. Tecentriq may be used with the medicines cobimetinib and vemurafenib in patients with melanoma when their skin cancer:

• has spread to other parts of the body or cannot be removed by surgery, and
• has a certain type of abnormal “BRAF” gene. Healthcare providers will perform a test to make sure this Tecentriq combination is right for the patient.

Adults and children 2 years of age and older with a type of soft tissue tumor (cancer) called alveolar soft part sarcoma (ASPS). Tecentriq may be used when their sarcoma:

• has spread to other parts of the body or cannot be removed by surgery.

It is not known if Tecentriq is safe and effective when used:

• in children younger than 2 years of age for the treatment of ASPS.
• in children for the treatment of NSCLC, SCLC, HCC or melanoma.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended.

Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including:

Lung problems

• cough
• shortness of breath
• chest pain

Intestinal problems

• diarrhea (loose stools) or more frequent bowel movements than usual
• stools that are black, tarry, sticky, or have blood or mucus
• severe stomach-area (abdomen) pain or tenderness

Liver problems

• yellowing of the skin or the whites of the eyes
• severe nausea or vomiting
• pain on the right side of their stomach area (abdomen)
• dark urine (tea colored)
• bleeding or bruising more easily than normal

Hormone gland problems

• headaches that will not go away or unusual headaches
• eye sensitivity to light
• eye problems
• rapid heartbeat
• increased sweating
• extreme tiredness
• weight gain or weight loss
• feeling more hungry or thirsty than usual
• urinating more often than usual
• hair loss
• feeling cold
• constipation
• their voice gets deeper
• dizziness or fainting
• changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness

Kidney problems

• decrease in their amount of urine
• blood in their urine
• swelling of their ankles
• loss of appetite

Skin problems

• rash
• itching
• skin blistering or peeling
• painful sores or ulcers in mouth or nose, throat, or genital area
• fever or flu-like symptoms
• swollen lymph nodes

Problems can also happen in other organs.

These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including:

• Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
• Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
• Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
• Persistent or severe muscle pain or weakness, muscle cramps
• Low red blood cells, bruising

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

• chills or shaking
• itching or rash
• flushing
• shortness of breath or wheezing
• dizziness
• feeling like passing out
• fever
• back or neck pain

Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq. A healthcare provider will monitor for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to 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 received an organ transplant
• have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
• have received radiation treatment to their chest area
• have a condition that affects their nervous system, such as myasthenia gravis or Guillain-Barré syndrome
• 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. Females who 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. Patients should 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 when used alone include:

• feeling tired or weak
• decreased appetite
• nausea
• cough
• shortness of breath

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

• feeling tired or weak
• nausea
• hair loss
• constipation
• diarrhea
• decreased appetite

The most common side effects of Tecentriq when used in hepatocellular carcinoma (HCC) with bevacizumab include:

• high blood pressure
• feeling tired or weak
• too much protein in the urine

The most common side effects of Tecentriq when used in melanoma with cobimetinib and vemurafenib include:

• skin rash
• joint, muscle, or bone pain
• feeling tired or weak
• liver injury
• fever
• nausea
• itching
• swelling of legs or arms
• mouth swelling (sometimes with sores)
• low thyroid hormone levels
• sunburn or sun sensitivity

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 about the benefits and side effects of Tecentriq.

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 see http://www.Tecentriq.com for full Prescribing Information and additional Important Safety Information.

Avastin is approved for:

Avastin, in combination with atezolizumab, is indicated for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

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.

• GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
• 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
• 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
• 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-related 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, therefore women should not breastfeed 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 1-800-FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

For full Prescribing Information and Boxed WARNINGS on Avastin please visit http://www.avastin.com.

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentech’s approved PD-L1 checkpoint inhibitor, the company’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. 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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