Friday, Sep 27, 2019

Genentech’s Tecentriq (Atezolizumab) Improves Overall Survival as a First-Line Monotherapy in Certain People With Advanced Non-Small Cell Lung Cancer

Phase III IMpower110 study showed Tecentriq monotherapy helped people with advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression live longer compared with chemotherapy alone

Data will be shared with health authorities globally, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)

South San Francisco, CA -- September 27, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced positive data from the Phase III IMpower110 study evaluating Tecentriq ^® (atezolizumab) as a first-line (initial) monotherapy compared with cisplatin or carboplatin and pemetrexed or gemcitabine (chemotherapy) in advanced non-squamous and squamous non-small cell lung cancer (NSCLC) without ALK or EGFR mutations (wild-type; WT).

The study met its primary endpoint in an interim analysis showing that Tecentriq monotherapy improved overall survival (OS) by 7.1 months compared with chemotherapy alone (median OS=20.2 versus 13.1 months; hazard ratio [HR]=0.595, 95% CI: 0.398–0.890; p=0.0106) in people with high PD-L1 expression (TC3/IC3-WT). Encouraging OS (18.2 versus 14.9 months; HR=0.717, 95% CI: 0.520–0.989) was also observed in people with medium levels of PD-L1 expression (TC2/3 or IC2/3-WT), however these data did not reach statistical significance at this interim analysis. The study will continue to final analysis for people with lower levels of PD-L1 expression. Safety for Tecentriq appeared to be consistent with its known safety profile, and no new safety signals were identified.

“We are excited to share these positive data, showing that Tecentriq alone offers a significant survival benefit over chemotherapy as an initial treatment in people with squamous or non-squamous non-small cell lung cancer with high PD-L1 expression,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “The IMpower110 results demonstrate the potential of first-line Tecentriq monotherapy in certain types of advanced lung cancer, and could provide an additional treatment option for oncologists and the patients that they treat.”

These data will be presented at the European Society for Medical Oncology (ESMO) 2019 Congress on Friday, September 27, 2019 from 4:00 – 5:30 p.m. CEST (Abstract LBA78; Barcelona Auditorium – Hall 2).

Genentech will submit these data to global health authorities, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), and will discuss how best to bring this option to patients as quickly as possible.

Currently, Genentech has nine Phase III lung cancer studies underway evaluating Tecentriq as a monotherapy or in combination with other medicines across different types of lung cancer. 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.

About the IMpower110 study
IMpower110 is a Phase III, randomized, open-label study to evaluate the efficacy and safety of Tecentriq monotherapy compared with cisplatin or carboplatin and pemetrexed or gemcitabine (chemotherapy) in programmed death-ligand 1 (PD-L1)-selected, chemotherapy-naive participants with advanced non-squamous or squamous NSCLC without ALK or EGFR mutations (wild-type; WT).

A total of 572 people (555 WT) were enrolled and were randomized 1:1 to receive:

• Tecentriq monotherapy, until loss of clinical benefit (as assessed by the investigator), unacceptable toxicity or death; or
• Cisplatin or carboplatin (per investigator discretion) combined with either pemetrexed (non-squamous) or gemcitabine (squamous), followed by maintenance therapy with pemetrexed alone (non-squamous) or best supportive care (squamous) until disease progression, unacceptable toxicity or death.

The primary efficacy endpoint is OS by PD-L1 subgroup (TC3/IC3-WT; TC2/3/ IC2/3-WT; and TC1,2,3/IC1,2,3-WT), as determined by the SP142 assay test. Key secondary endpoints include investigator-assessed progression-free survival (PFS), objective response rate (ORR) and duration of response (DoR).

An overview of the key OS results is below:

	Median OS
	Arm A (Tecentriq)		Arm B (chemo)		HRa 95% CI	P Value
	n	months	n	months
TC3 or IC3-WT	107	20.2	98	13.1	0.595 (0.398, 0.890)	0.0106
TC2/3 or IC2/3-WT*	166	18.2	162	14.9	0.717 (0.520, 0.989)	0.0416
TC1/2/3 or IC1/2/3-WT**	277	17.5	277	14.1	0.832 (0.649, 1.067)	0.1481b
TC, tumor cell; IC, tumor-infiltrating immune cells. PD-L1 expression was centrally evaluated with the VENTANA SP142 IHC assay. TC3 or IC3 = TC ≥ 50% or IC ≥ 10% PD-L1+; TC1/2/3 or IC1/2/3 = TC ≥ 1% or IC ≥ 1% PD-L1+; TC2/3 or IC2/3 = TC ≥ 5% or IC ≥ 5% PD-L1+. a Stratified. b Only for descriptive purpose. *TC2/3 or IC2/3-WT did not cross the pre-specified boundary for statistical significance **TC1/2/3 or IC1/2/3-WT was not formally tested and did not meet statistical significance

The safety population comprised 286 patients in Arm A and 263 in Arm B. Treatment-related AEs (TRAEs) and Grade 3-4 TRAEs occurred in 60.5% (Arm A) and 85.2% (Arm B), and 12.9% (Arm A) and 44.1% (Arm B), respectively.

About lung cancer

According to the American Cancer Society, it is estimated that more than 228,000 Americans will be diagnosed with lung cancer in 2019, and NSCLC accounts for 80-85% of all lung cancers. It is estimated that approximately 60% of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.

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 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”, and
  • 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 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 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:
  • 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
• 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

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.

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 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 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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