FDA Approves Genentech’s Tecentriq plus Cotellic and Zelboraf for People With Advanced Melanoma

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) approved Tecentriq ^® (atezolizumab) plus Cotellic ^® (cobimetinib) and Zelboraf ^® (vemurafenib) for the treatment of BRAF V600 mutation-positive advanced melanoma patients. The safety profile observed in the Tecentriq combination was consistent with the known safety profiles of the individual medicines.

The supplemental Biologics License Application (sBLA) for Tecentriq was granted under Priority Review. The review was also conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology products among international partners.

“When receiving a cancer immunotherapy combined with targeted therapies, patients with BRAF V600 mutation-positive advanced melanoma were able to live for more than 15 months without their disease worsening,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Today’s FDA approval of this Tecentriq combination represents an important step forward for many patients living with advanced melanoma.”

The approval is based on results from the Phase III IMspire150 study, in which the addition of Tecentriq to Cotellic and Zelboraf helped people live longer without their disease worsening or death (progression-free survival, PFS), compared to placebo plus Cotellic and Zelboraf (median PFS 15.1 months versus 10.6 months respectively; hazard ratio, HR=0.78; confidence interval: 0. (Read more…)63-0.97; P=0.025). The most common adverse reactions (rate ≥20%) in patients who received Tecentriq plus Cotellic and Zelboraf were rash (75%), musculoskeletal pain (62%), fatigue (51%), hepatotoxicity (50%), pyrexia (49%), nausea (30%), pruritus (26%), edema (26%), stomatitis (23%), hypothyroidism (22%), and photosensitivity reaction (21%).

Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across lung, genitourinary, skin, breast, gastrointestinal, gynecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

For those who qualify, Genentech will offer patient assistance programs for people prescribed Tecentriq plus Cotellic and Zelboraf by their doctor through Genentech Access Solutions. Please contact Genentech Access Solutions at (866) 422-2377 or visit http://www.Genentech-Access.com for more information.

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 U.S. 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 in patients with urothelial carcinoma if their bladder cancer has spread or cannot be removed by surgery, and if they have any one of the following conditions:

• They are not able to take chemotherapy that contains a medicine called cisplatin and their cancer tests positive for “PD-L1” or
• They are not able to take chemotherapy that contains any platinum regardless of the levels of “PD-L1” status or
• They 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 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 non-small cell lung cancer (NSCLC).

Tecentriq may be used alone as the first treatment in patients with lung cancer if:

• Their 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 the first treatment in patients with lung cancer if:

• Their 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 the first treatment in patients with lung cancer if:

• Their 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 in patients with lung cancer if:

• Their cancer has spread or grown and
• They have tried chemotherapy that contains platinum, and it did not work or is no longer working.
• If a patient’s 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.

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

Tecentriq may be used with the medicine paclitaxel protein-bound in patients with TNBC when their breast cancer:

• Has spread or cannot be removed by surgery and
• Their 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 the first treatment in patients with SCLC when their lung cancer is a type of lung cancer called “extensive-stage small cell lung cancer,” which means that it has spread or grown.

A type of liver cancer called hepatocellular carcinoma (HCC).

Tecentriq may be used with the medicine bevacizumab when a patient’s liver cancer:

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

A type of skin cancer called melanoma.

Tecentriq may be used with the medicines cobimetinib and vemurafenib when a patient’s melanoma:

• Has spread or cannot be removed by surgery, and
• Their cancer has a certain type of abnormal “BRAF” gene. Their healthcare provider will perform a test to make sure this Tecentriq combination is right for them.

It is not known if Tecentriq is safe and effective in children.

Important Safety Information

The most important information about Tecentriq is:

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 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 mucus in 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.
  
  Females who are able to become pregnant:
  • Should have a healthcare provider do a pregnancy test before they start treatment with Tecentriq and
  • 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 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
• 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
• Nausea
• Hair loss
• Constipation
• Diarrhea
• Decreased appetite

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

• Hair loss
• Tingling or numbness in hands and feet
• Feeling tired
• Nausea
• Diarrhea
• Low red blood cells (anemia)
• Constipation
• Cough
• Headache
• Low white blood cells
• Vomiting
• Decreased appetite

The most common side effects of Tecentriq when used in hepatocellular carcinoma 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
• Pain in the joint, muscle, or bone
• Feeling tired or weak
• Liver injury
• Fever
• Nausea
• Itching
• Swelling of legs or arms
• Swelling of the mouth (sometimes with sores)
• Low thyroid hormone levels
• Vomiting
• Skin sensitivity to sunlight

Tecentriq may cause fertility problems in females, which may affect their 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 of Tecentriq.

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.

Please visit http://www.Tecentriq.com for the full Tecentriq Prescribing Information for additional Important Safety Information.

Cotellic U.S. Indication (pronounced ‘co-TELL-ic’)

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 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 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 a history of skin problems other than melanoma
• Have bleeding problems, or a higher risk of bleeding because of medical conditions or medications
• 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
    • Talk to their healthcare provider about birth control methods that may be right for them.
    • 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 to 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 and should take their next dose as scheduled.
• If a patient misses a dose of Cotellic, they should take their next dose as scheduled.

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

• Should wear clothes that protect their skin, including their head, face, hands, arms and legs, and
• Should use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.

Cotellic can cause serious side effects, including a risk of cancer. Cotellic may cause new skin cancers such as:

• Cutaneous squamous cell carcinoma (cuSCC)
• Keratoacanthoma
• Basal cell carcinoma (BCC)

Patients should check their skin regularly and tell their healthcare provider right away if they have 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

When taking Cotellic, a patient’s healthcare provider should check their skin to look for any new skin cancers:

• Before they start taking Cotellic and
• Every two months during treatment with Cotellic and
• May continue to check their 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. Cotellic can cause serious side effects, including:

• 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, such as:
  • 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 about eye problems right away, including:
  • Blurred vision
  • Partly missing vision or loss of vision
  • Seeing halos
  • Any other vision change
    
    A patient’s healthcare provider should check their eyes if the patient notices any of the symptoms.
• 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). An increased level of CPK in the blood 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 do 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 levels of phosphate, sodium or potassium
• Increased blood levels 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.

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.

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

Zelboraf U.S. Indication (pronounced ‘ZEL-bor-af’)

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 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

The most important information about Zelboraf is:

Zelboraf can affect the way normal organs and tissues work. These problems can sometimes become serious.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Contacts

Media Contact:

K. Bruneau (650) 467-6800

Advocacy Contact:

Lauren Davis (650) 745-5210

Investor Contacts:

Loren Kalm (650) 225-3217

Karl Mahler 011 41 61 687 8503

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