Genentech’s Novel Anti-TIGIT Tiragolumab Granted FDA Breakthrough Therapy Designation in Combination With Tecentriq for PD-L1-High Non-Small Cell Lung Cancer

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA), in combination with Tecentriq^® (atezolizumab) for the first-line treatment of people with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression with no EGFR or ALK genomic tumor aberrations. Tiragolumab is the first anti-TIGIT molecule to be granted BTD from the FDA, and the designation is based on randomized data from the Phase II CITYSCAPE trial. CITYSCAPE provides the first evidence that targeting both immune inhibitory receptors, TIGIT and PD-L1, may enhance anti-tumor activity by potentially amplifying the immune response.

“We have been researching TIGIT as a novel cancer immunotherapy target for almost 10 years and we are pleased that the FDA has acknowledged the potential of tiragolumab to substantially improve outcomes for people with certain types of lung cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We look forward to advancing our tiragolumab development program, which includes chemotherapy-free combinations and trials in early stages of disease across multiple cancer types with high unmet need.”

BTD is designed to accelerate the development and review of medicines intended to treat serious or life-threatening conditions, with preliminary evidence that indicates they may demonstrate a substantial improvement over existing therapies. This marks the 37th BTD for Genentech’s portfolio of medicines.

Tiragolumab in combination with Tecentriq has so far shown encouraging efficacy and safety in PD-L1-positive metastatic NSCLC based on data from the Phase II CITYSCAPE trial, the first randomized study in the anti-TIGIT field. Full results from CITYSCAPE, presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program, showed that at an average of 10.9 months follow-up, the combination showed an improvement in the overall response rate (ORR; 37% vs. 21% with Tecentriq alone) and a 42% reduction in the risk of disease worsening or death (progression-free survival; PFS) compared with Tecentriq alone. An exploratory analysis in people with high levels of PD-L1 (tumor proportion score; TPS ≥ 50%) showed a clinically meaningful ORR vs. Tecentriq alone (66% vs. 24%) and median PFS was not reached (vs. 4.11 months with Tecentriq alone; HR=0.30, 95% CI: 0.15–0.61). The data suggest that tiragolumab plus Tecentriq was generally well-tolerated, showing similar rates of all Grade 3 or more all-cause adverse events when combining the two immunotherapies compared with Tecentriq alone (48% vs. 44%).

Genentech is investigating the potential of tiragolumab in a broad development program that builds on the benefit observed with Tecentriq while expanding into earlier stages of disease and new areas of unmet need. This includes randomized trials in metastatic NSCLC (SKYSCRAPER-01 and SKYSCRAPER-06) and small cell lung cancer (SKYSCRAPER-02), as well as exploration of tiragolumab in earlier stages, including stage III NSCLC (SKYSCRAPER-03) and locally advanced esophageal cancer (SKYSCRAPER-07). Tiragolumab is also being investigated in metastatic esophageal squamous cancer (SKYSCRAPER-08) and cervical cancer (SKYSCRAPER-04), with early trials in other tumor types.

Biomarker analyses from the CITYSCAPE study will be presented at the IASLC 2020 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, taking place from January 28-31, 2021 (Efficacy of Tiragolumab + Atezolizumab in PD-L1 IHC and TIGIT Subgroups in the Phase II CITYSCAPE Study in First-Line NSCLC).

Dual blockade of the TIGIT and PD-L1 pathways

TIGIT and PD-L1 are proteins that play a role in suppression of the immune system. Blocking both pathways simultaneously with tiragolumab and Tecentriq has the potential to increase anti-tumor activity by enhancing the body’s immune response to cancer cells. Targeting multiple immune pathways in this way has the potential to build upon previous advances in cancer immunotherapy, expand into earlier stages of disease and provide new treatment options in areas of high unmet need.

About the CITYSCAPE study

CITYSCAPE is a global Phase II, randomized and blinded study evaluating tiragolumab plus Tecentriq^® (atezolizumab) compared with Tecentriq alone in 135 patients with first-line PD-L1-positive, locally advanced unresectable or metastatic non-small cell lung cancer. Patients were randomized 1:1 to receive either tiragolumab plus Tecentriq or placebo plus Tecentriq, until progressive disease or loss of clinical benefit. Co-primary endpoints are overall response rate and progression-free survival. Secondary endpoints include safety and overall survival.

About tiragolumab

Tiragolumab is a monoclonal antibody designed to bind with TIGIT, a protein receptor on immune cells. Tiragolumab works as an immune amplifier, by potentially enhancing the body’s immune response. By binding to TIGIT, tiragolumab blocks its interaction with a protein called poliovirus receptor (PVR, or CD155) that can suppress the body’s immune response. Blockade of TIGIT and PD-L1 may synergistically enable the re-activation of T cells and enhance NK cell anti-tumor activity.

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.

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)
• Underactive thyroid gland
• 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.

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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