Genentech Announces Phase III Study Results for Tecentriq Plus Cotellic and Zelboraf in People With Previously Untreated BRAF V600 Mutation-positive Advanced Melanoma

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced the Phase III IMspire150 study, in people with previously untreated BRAF V600 mutation-positive advanced melanoma, met its primary endpoint of progression-free survival (PFS). The study showed adding Tecentriq^® (atezolizumab) to Cotellic^® (cobimetinib) and Zelboraf^® (vemurafenib) helped to reduce the risk of disease worsening or death, compared to placebo plus Cotellic and Zelboraf.

A significant and clinically meaningful improvement in PFS was demonstrated in the study. The safety profile observed in IMspire150 was consistent with the known safety profiles of the individual medicines. Results from the study will be presented at an upcoming medical meeting and discussed with health authorities, including the U.S. Food and Drug Administration and European Medicines Agency.

“By combining a cancer immunotherapy with targeted therapies, we hope to offer a new approach that improves outcomes for people with advanced, BRAF-mutant melanoma,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We look forward to discussing the results with health authorities around the world.”

Genentech has an extensive clinical trial development program for Tecentriq, with more than 50 ongoing studies, including multiple Phase III studies across lung, kidney, skin, breast, colorectal, prostate, ovarian, bladder, blood, liver and head and neck cancers. Studies are evaluating Tecentriq alone and in combination with other medicines.

About the IMspire150 study

IMspire150 is a Phase III, multi-center, double-blind, placebo-controlled randomized study in people with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma. The study compared the efficacy and safety of Tecentriq plus Cotellic and Zelboraf to the combination of placebo plus Cotellic and Zelboraf. The primary endpoint of the study was investigator-assessed PFS. Key secondary endpoints include PFS by an independent review committee, overall survival, objective response rate, duration of response and other safety and pharmacokinetic measures.

About advanced melanoma

Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer. When melanoma is diagnosed early, it is generally a curable disease, but most people with advanced melanoma have a poor prognosis. The American Cancer Society estimates there will be more than 96,000 new cases of melanoma and 7,000 melanoma deaths this year in the United States.

In recent years, there have been significant advances in treatment for advanced melanoma and people with the disease have more options. However, it continues to be a serious health issue with a high medical need and a steadily increasing incidence over the past 30 years.

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 Cotellic (cobimetinib)

Cotellic is designed to inhibit MEK1/2, proteins in a cell signaling pathway that helps control cell growth and survival. Cotellic, when used in combination with Zelboraf, is approved in the United States and Europe, as well as many countries around the world, for the treatment of people with melanoma that has spread to other parts of the body or cannot be removed by surgery and has a BRAF V600 mutation. Cotellic was discovered by Exelixis and is being developed by Genentech, a member of the Roche Group, in collaboration with Exelixis.

About Zelboraf (vemurafenib)

Zelboraf is a prescription medicine for the treatment of people with melanoma that has spread to other parts of the body or cannot be removed by surgery and has a BRAF V600 mutation. Zelboraf is designed to inhibit some mutated forms of BRAF, which cause abnormal signaling inside cancer cells leading to tumor growth. BRAF is a protein in a cell signaling pathway that helps control cell growth and survival. Zelboraf was the first approved product in its class. Zelboraf was co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon Inc., the small molecule structure-guided R&D center of the Daiichi Sankyo Group.

Tecentriq Indications (pronounced ‘tē-SEN-trik’)

Tecentriq is a prescription medicine used to treat adults with:

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 cancer tests positive for “PD-L1”, or
  • you are not able to take chemotherapy that contains any platinum regardless of the levels of “PD-L1” status, 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. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

A type of lung cancer called non-small cell lung cancer (NSCLC).

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

• Tecentriq may be used alone 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, and
  • 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.

A type of breast cancer called triple-negative breast cancer (TNBC).

Tecentriq may be used with the medicine paclitaxel protein-bound when your breast cancer:

• has spread or cannot be removed by surgery, and
• your cancer tests positive for “PD-L1”

The approval of TECENTRIQ in these patients is based on a study that measured the amount of time until patients’ disease worsened. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

A type of lung cancer called small cell lung cancer (SCLC).

• Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as your first treatment when your lung cancer:
  • is a type of lung cancer called “extensive-stage small cell lung cancer,” which means that it has spread or grown.

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 of pneumonitis may include new or worsening cough, shortness of breath, and chest pain
• Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of your skin or the whites of your 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 mucus in your 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 your 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. 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
• nausea
• constipation
• cough
• shortness of breath
• decreased appetite

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

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

The most common side effects of Tecentriq when used with paclitaxel protein-bound include:

• hair loss
• feeling tired
• tingling or numbness in hands and feet
• nausea
• diarrhea
• low red blood cells (anemia)
• constipation
• cough
• headache
• low white blood cells
• decreased appetite
• vomiting

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.

Cotellic Indication

Important: If a patient’s healthcare provider prescribes Zelboraf (vemurafenib), the patient should also read the Medication Guide that comes with Zelboraf.

Cotellic is a prescription medicine that is used with the medicine Zelboraf to treat a type of skin cancer called melanoma:

• that has spread to other parts of the body or cannot be removed by surgery, and
• that has a certain type of abnormal “BRAF” gene.

A patient’s healthcare provider will perform a test to make sure that Cotellic is right for the patient. It is not known if Cotellic is safe and effective in children under 18 years of age.

Important Safety Information

Before taking Cotellic, patients should tell their healthcare provider about all of their medical conditions, including if they:

• have skin problems or history of skin problems, other than melanoma
• have bleeding problems, any medical conditions and/or on any medications that increase the risk of bleeding
• have heart problems
• have eye problems
• have liver problems
• have muscle problems
• are pregnant or plan to become pregnant. Cotellic can harm an unborn baby.
  • Females who are able to become pregnant should use effective birth control during treatment with Cotellic, and for two weeks after the final dose of Cotellic.
  • Patients should talk to their healthcare provider about birth control methods that may be right for them.
  • Patients should tell their healthcare provider right away if they become pregnant or think they are pregnant during treatment with Cotellic.

• are breastfeeding or plan to breastfeed. It is not known if Cotellic passes into breast milk. Patients should not breastfeed during treatment with Cotellic and for two weeks after the final dose of Cotellic. Patients should talk to their healthcare provider about the best way to feed their baby during this time.

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Certain medicines may affect the blood levels of Cotellic.

Patients should know the medicines they take and keep a list of them to show their healthcare provider and pharmacist when they get a new medicine.

How should patients take Cotellic?

• Patients should take Cotellic exactly as their healthcare provider tells them. Patients should not change their dose or stop taking Cotellic unless their healthcare provider tells them to.
• Patients should take Cotellic one time a day for 21 days, followed by seven days off treatment, to complete a 28-day treatment cycle.
• Patients can take Cotellic with or without food.
• If a patient vomits after taking their dose of Cotellic, they should not take an additional dose. Patients should take their next dose as scheduled.
• If a patient misses a dose of Cotellic, they should take their next dose as scheduled.

What should patients avoid during treatment with Cotellic?

Patients should avoid sunlight during treatment with Cotellic. Cotellic can make a patient’s skin sensitive to sunlight. They may burn more easily and get severe sunburns. To help protect against sunburn:

• When a patient goes outside, they should wear clothes that protect their skin, including their head, face, hands, arms and legs.
• They should use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.

What are the possible side effects of Cotellic?

Cotellic may cause serious side effects, including:

• Risk of new skin cancers. Cotellic may cause new skin cancers (cutaneous squamous cell carcinoma, keratoacanthoma or basal cell carcinoma).

  Patients should check their skin regularly and tell their healthcare provider right away if they have any skin changes including:

• new wart
• skin sore or reddish bump that bleeds or does not heal
• change in size or color of a mole

A patient’s healthcare provider should check the patient’s skin before they start taking Cotellic, and every two months during treatment with Cotellic. A patient’s healthcare provider may continue to check the patient’s skin for six months after the patient stops taking Cotellic.

A patient’s healthcare provider should also check for cancers that may not occur on the skin. Patients should tell their healthcare provider about any new symptoms that develop during treatment with Cotellic.

• Bleeding problems. Cotellic can cause serious bleeding problems.
  Patients should call their healthcare provider and get medical attention right away if they get any signs of bleeding, including:
  • red or black stools (looks like tar)
  • blood in their urine
  • headaches
  • cough up or vomit blood
  • stomach (abdominal) pain
  • unusual vaginal bleeding
  • dizziness or weakness

• Heart problems. A patient’s healthcare provider should do tests before and during treatment to check the patient’s heart function. Patients should tell their healthcare provider if they get any of these signs and symptoms of heart problems:
  • persistent coughing or wheezing
  • shortness of breath
  • swelling of their ankles and feet
  • tiredness
  • increased heart rate

• Severe rash. Patients should tell their healthcare provider right away if they get any of these symptoms:
  • a rash that covers a large area of their body
  • blisters
  • peeling skin

• Eye problems. Patients should tell their healthcare provider right away if they get any of these symptoms:
  • blurred vision
  • partly missing vision or loss of vision
  • see halos
  • any other vision change

A patient’s healthcare provider should check the patient’s eyes if the patient notices any of the symptoms above.

• Liver problems. A patient’s healthcare provider should do blood tests to check the patient’s liver function before and during treatment. Patients should tell their healthcare provider right away if they get any of these symptoms:
  • yellowing of their skin or the white of their eyes
  • dark or brown (tea color) urine
  • nausea or vomiting
  • feeling tired or weak
  • loss of appetite

• Muscle problems (rhabdomyolysis). Cotellic can cause muscle problems that can be severe. Treatment with Cotellic may increase the level of an enzyme in the blood called creatine phosphokinase (CPK) and may be a sign of muscle damage. A patient’s healthcare provider should do a blood test to check the patient’s levels of CPK before and during treatment. Patients should tell their healthcare provider right away if they get any of these symptoms:
  • muscle aches or pain
  • muscle spasms and weakness
  • dark, reddish urine

• Skin sensitivity to sunlight (photosensitivity). Skin sensitivity to sunlight during treatment with Cotellic is common and can sometimes be severe. Patients should tell their healthcare provider if they get any of these symptoms:
  • red, painful, itchy skin that is hot to touch
  • sun rash
  • skin irritation
  • bumps or tiny papules
  • thickened, dry, wrinkled skin

See “What should patients avoid during treatment with Cotellic?” for information on protecting the skin during treatment with Cotellic.

The most common side effects of Cotellic include:

• diarrhea
• nausea
• fever
• vomiting

A patient’s healthcare provider will take blood tests during treatment with Cotellic. The most common changes to blood tests include:

• increased blood levels of liver enzymes (GGT, ALT or AST)
• increased blood level of enzyme from muscle (creatine phosphokinase)
• decreased blood level of phosphate, sodium or potassium
• increased blood level of liver or bone enzyme (alkaline phosphatase)
• decreased blood level of a type of white blood cell (lymphocyte)

These are not all the possible side effects of Cotellic. Patients should call their doctor for medical advice about side effects. Patients may report side effects to FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at (888) 835-2555.

Please see Full Cotellic Prescribing Information and Patient Information for additional Important Safety Information at http://www.cotellic.com/.

Zelboraf Indication

Zelboraf is a prescription medicine used to treat a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal “BRAF” gene.

A patient’s healthcare provider will perform a test to make sure that Zelboraf is right for them.

Zelboraf is not used to treat melanoma with a normal BRAF gene. It is not known if Zelboraf is safe and effective in children under 18 years of age.

Important Safety Information

What is the most important information patients should know about Zelboraf?

Zelboraf can cause serious side effects, including:

• Risk of cancers. Zelboraf may cause a type of skin cancer called cutaneous squamous cell carcinoma (cuSCC). New melanoma lesions have occurred in people who take Zelboraf. Zelboraf may also cause another type of cancer called non-cutaneous squamous cell carcinoma (SCC). Patients should talk with their healthcare provider about their risk for these cancers.

Patients should check their skin and tell their healthcare provider right away about any skin changes, including a:

• new wart
• skin sore or reddish bump that bleeds or does not heal
• change in size or color of a mole

A patient’s healthcare provider should check their skin before they start taking Zelboraf, and every two months while they are taking Zelboraf, to look for any new skin cancers. A patient’s healthcare provider may continue to check their skin for six months after they stop taking Zelboraf.

A patient’s healthcare provider should also check for cancers that may not occur on the skin. Patients should tell their healthcare provider about any new symptoms that they get while taking Zelboraf.

What should patients tell their healthcare provider before taking Zelboraf?

Before patients take Zelboraf, they should tell their healthcare provider if they:

• Have any heart problems, including a condition called long QT syndrome
• Have liver or kidney problems
• Have had or are planning to receive radiation therapy
• Have been told that they have low blood levels of potassium, calcium, or magnesium
• Have any other medical conditions
• Are pregnant or plan to become pregnant. Zelboraf can harm an unborn baby.
  • Females who are able to become pregnant should use effective birth control during Zelboraf treatment and for two weeks after the final dose
  • Patients should talk to their healthcare provider about birth control methods that may be right for them
  • Patients should tell their healthcare provider right away if they become pregnant during treatment with Zelboraf

• Are breastfeeding or plan to breastfeed. It is not known if Zelboraf passes into breast milk. Patients should not breastfeed during treatment with Zelboraf and for two weeks after the final dose. Patients should talk to their healthcare provider about the best way to feed their baby during this time.

Patients should tell their healthcare provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Patients should know the medicines they take. Patients should keep a list of them to show their healthcare provider and pharmacist when they get a new medicine.

What should patients avoid while taking Zelboraf?

Patients should avoid sunlight while they are taking Zelboraf. Zelboraf can make a patient’s skin sensitive to sunlight. Patients may burn more easily and get severe sunburns. To help protect against sunburn:

• When patients go outside, they should wear clothes that protect their skin, including their head, face, hands, arms, and legs.
• Patients should use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.

What are the possible side effects of Zelboraf?

• Allergic reactions can happen while taking Zelboraf, and can be severe. Patients should stop taking Zelboraf and get medical help right away if they get any of these symptoms of an allergic reaction:
  • Rash or redness all over their body
  • Trouble breathing or swallowing
  • Swelling of the face, lips, or tongue
  • Throat tightness or hoarseness
  • Feel faint
  • Fast heartbeat

• Severe skin reactions. Patients should stop taking Zelboraf and call their healthcare provider right away if they get a skin rash with any of the following symptoms, because they may have a severe skin reaction:
  • Blisters on their skin
  • Blisters or sores in their mouth
  • Peeling of their skin
  • Fever
  • Redness or swelling of their face, hands, or soles of their feet

• Changes in the electrical activity of the heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life-threatening. A patient’s healthcare provider should do tests before they start taking Zelboraf and during treatment with Zelboraf to check the electrical activity of their heart. Patients should tell their healthcare provider right away if they feel faint, lightheaded, dizzy, or feel their heart beating irregularly or fast while taking Zelboraf. These may be symptoms related to QT prolongation.

• Liver injury. A patient’s healthcare provider should do blood tests to check their liver function before they start taking Zelboraf and during treatment. Patients should tell their healthcare provider right away if they get any of these symptoms of a liver problem during treatment:
  • Yellowing of their skin or the white part of their eyes
  • Dark or brown (tea color) urine
  • Nausea or vomiting
  • Loss of appetite
  • Pain on the right side of their stomach

• Eye problems. Patients should tell their healthcare provider right away if they get any of these symptoms during treatment with Zelboraf:
  • Eye pain, swelling, or redness
  • Blurred vision or other vision changes

• Worsening side effects from radiation treatment. Patients should tell their healthcare provider if they have had or are planning to receive radiation therapy.

• Kidney injury. A patient’s healthcare provider should do blood tests to check their kidney function before they start taking Zelboraf and during treatment.

The most common side effects include:

• Joint pain
• Rash
• Hair loss
• Tiredness
• Sunburn or sun sensitivity
• Nausea
• Itching
• Warts

Patients should tell their healthcare provider if they have any side effect that bothers them or does not go away. These are not all of the possible side effects of Zelboraf. For more information about side effects, patients should ask their healthcare provider or pharmacist. Patients should call their doctor for medical advice about side effects.

Patients may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at (888) 835-2555.

Please see Full Prescribing Information and Medication Guide for additional Important Safety Information at http://www.zelboraf.com/.

About Genentech in skin cancer

Genentech has been studying new treatments for skin cancer for more than 20 years. We continue to study our skin cancer medicines in combination with other medicines, including cancer immunotherapies, in several types of cancer.

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 currently studying more than 10 cancer immunotherapy medicines across 70 clinical trials alone or in combination with other medicines. 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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