Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the Phase III IMblaze370 study evaluating the combination of TECENTRIQ^® (atezolizumab) and COTELLIC ^® (cobimetinib) did not meet its primary endpoint of overall survival (OS) compared to regorafenib. The study evaluated the combination in people with difficult-to-treat, locally advanced or metastatic colorectal cancer (CRC) whose disease progressed or who were intolerant to at least two systemic chemotherapy regimens.

More than 95 percent of patients in IMblaze370 have microsatellite stable (MSS) tumors and based on the available data, checkpoint inhibitors as monotherapy have not demonstrated clinically meaningful efficacy in MSS mCRC. The results from IMblaze370 were consistent with this prior monotherapy experience, showing that treatment with TECENTRIQ alone did not provide a meaningful clinical benefit compared to regorafenib in this patient population.

Safety for the combination of TECENTRIQ and COTELLIC appeared to be consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination. The results from IMblaze370 will be further examined and presented at an upcoming medical meeting.

“While these results are not what we hoped for, we remain committed to applying our deep experience to develop medicines that will improve outcomes for people living with gastrointestinal cancers,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “In particular, we have a number of studies evaluating medicines in colorectal cancer that could play an important role in the treatment of people with this disease in the future.”

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

About the IMblaze370 study

IMblaze370 is a Phase III, multi-center, open-label, three-arm, randomized study in people with difficult-to-treat locally advanced or metastatic colorectal cancer who have received at least two prior regimens of chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to COTELLIC plus TECENTRIQ and TECENTRIQ monotherapy. The study enrolled 363 people who were randomized (2:1:1) to receive:

• TECENTRIQ plus COTELLIC, or
• TECENTRIQ, or
• Regorafenib (control arm)

People in the combination arm received COTELLIC on days 1 to 21 plus TECENTRIQ on day 1 and day 15 in a 28-day cycle, until loss of clinical benefit. People in the monotherapy arm received TECENTRIQ on day 1 of each 21-day cycle, until loss of clinical benefit. People in the control arm received regorafenib on days 1 to 21 in a 28-day cycle, until loss of clinical benefit. The primary endpoint was overall survival. Key secondary endpoints include progression-free survival (PFS), overall response rate (ORR) and duration of response (DoR).

About colorectal cancer

According to the American Cancer Society, colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the United States and the third leading cause of cancer deaths. In 2018, an estimated 97,000 people will be diagnosed with colorectal cancer and about 50,000 people are expected to die from the disease in the United States. If colorectal cancer spreads (metastasizes) to distant organs, such as the lungs or the liver, five-year survival is 14 percent.

About the TECENTRIQ (atezolizumab) and COTELLIC (cobimetinib) combination

Based on our pre-clinical data and Phase Ib data there was a strong scientific rationale to support the further investigation of TECENTRIQ and COTELLIC. The IMblaze370 data will be further examined in order to better understand the results and presented at an upcoming medical meeting. Genentech is continuing to investigate the TECENTRIQ and COTELLIC combination in other tumor types, including the IMspire150 and IMspire170 studies in melanoma.

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 a prescription medicine used with Zelboraf for the treatment of people with 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. COTELLIC is not used to treat melanoma with a normal BRAF gene. COTELLIC was discovered by Exelixis Inc. and was developed by Genentech in collaboration with Exelixis. COTELLIC is also being investigated in combination with several investigational medicines, including TECENTRIQ, in several tumor types such as non-small cell lung cancer, melanoma and colorectal cancer.

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
  • you are not able to take chemotherapy that contains a medicine called cisplatin, 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. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with TECENTRIQ. If you are able to become pregnant:
• your healthcare provider should do a pregnancy test before you start treatment with TECENTRIQ
• You should use an effective method of birth control during your 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