Genentech Provides Update on Phase III SKYSCRAPER-02 Study in Extensive-Stage Small Cell Lung Cancer

– SKYSCRAPER-02, the first randomized study of tiragolumab in extensive-stage small cell lung cancer (ES-SCLC), did not meet its co-primary endpoint of progression-free survival –

– ES-SCLC is a hard-to-treat disease and Tecentriq plus chemotherapy remains a standard of care –

– Tiragolumab continues to be evaluated in non-small cell lung cancer and other cancer types through additional Phase III trials as planned –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the Phase III SKYSCRAPER-02 study, evaluating the investigational anti-TIGIT immunotherapy tiragolumab plus Tecentriq® (atezolizumab) and chemotherapy (carboplatin and etoposide) as an initial (first-line) treatment for people with extensive-stage small cell lung cancer (ES-SCLC), did not meet its co-primary endpoint of progression-free survival. The co-primary endpoint of overall survival was not met at its interim analysis and is unlikely to reach statistical significance at the planned final analysis. Data suggest tiragolumab plus Tecentriq and chemotherapy was well-tolerated and no new safety signals were identified when adding tiragolumab. Data will be presented at an upcoming medical meeting.

“Today’s outcome is disappointing as we had hoped to continue building on the advances of Tecentriq in extensive stage small-cell lung cancer, which remains difficult to treat. We are thankful to all the patients and healthcare professionals involved in the study,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We look forward to seeing additional data from the upcoming Phase III trial in PD-L1-high non-small cell lung cancer based on the encouraging results from the CITYSCAPE study.”

SCLC is the most aggressive form of any lung cancer and is characterized by rapid progression and poor survival. Tecentriq was the first cancer immunotherapy to show a survival benefit in ES-SCLC (Phase III IMpower133 study), and was the first approved treatment option in 20 years. More options are needed, particularly for hard-to-treat cancers like SCLC, and Genentech is committed to exploring innovative medicines to improve outcomes for people with lung cancer.

The tiragolumab program continues to explore advances in multiple clinical trials to build on Tecentriq, expand into earlier stages of disease, and seeks to provide new treatment options in advanced and difficult-to-treat cancers with high unmet medical need. Tiragolumab was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in 2021 for the initial treatment of PD-L1-high metastatic non-small cell lung cancer, based on the results of the Phase II CITYSCAPE study – representing the only investigational anti-TIGIT therapy to be granted this designation. The Phase III SKYSCRAPER-01 trial is currently ongoing to confirm the CITYSCAPE results. Since 2020, Genentech has initiated five Phase III trials, including NSCLC (SKYSCRAPER-01, SKYSCRAPER-03), ES-SCLC (SKYSCRAPER-02), esophageal cancers (SKYSCRAPER-07, SKYSCRAPER-08), and multiple early trials in various tumor types.

About the SKYSCRAPER-02 study

SKYSCRAPER-02 is a global Phase III, randomized, placebo-controlled and double-blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) and chemotherapy as an initial (first-line) treatment versus Tecentriq and chemotherapy alone in 490 people with extensive-stage small cell lung cancer. Co-primary endpoints are overall survival (OS) and progression-free survival (PFS) in the primary analysis set (all randomized patients whose cancer had not spread to the brain). Key secondary endpoints include OS and PFS in all randomized patients, and safety.

About tiragolumab

Tiragolumab is a novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint, which suppresses the immune response to cancer. Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq® (atezolizumab). The TIGIT pathway is distinct but complementary to the PD-L1/PD-1 pathway. Dual blockade with tiragolumab and Tecentriq may help overcome immune suppression and restore the immune response.

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

Tecentriq is a prescription medicine used to treat 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 your first treatment when your lung cancer:

• TECENTRIQ may be used alone as a treatment for their lung cancer:
  • is a type 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 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

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 the Tecentriq full Prescribing Information, including the Medication Guide, 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 in lung cancer

Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

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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