Market Overview

Phase III IMmotion151 Study Showed Genentech's TECENTRIQ (Atezolizumab) and Avastin (Bevacizumab) Reduced the Risk of Disease Worsening or Death by 26 Percent in Certain People With Advanced Kidney Cancer

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– TECENTRIQ and Avastin met co-primary endpoint of
investigator-assessed progression-free survival (PFS) compared with
sunitinib for people whose disease expressed PD-L1 –

– IMmotion151 is the second Phase III study to show positive PFS
results for a treatment regimen including TECENTRIQ plus Avastin –

– Data will be discussed with global health authorities, including
the U.S. Food and Drug Administration (FDA) –

Genentech, a member of the Roche Group ((SIX: RO, ROG, OTCQX:RHHBY),
today announced results from the positive Phase III IMmotion151 study of
TECENTRIQ® (atezolizumab) and Avastin®
(bevacizumab) as a first-line treatment for advanced or metastatic renal
cell carcinoma (mRCC). The study met its co-primary endpoint of
investigator-assessed progression-free survival (PFS) in people whose
disease expressed the PD-L1 (programmed death-ligand 1: expression ≥ 1
percent) protein. Those who received TECENTRIQ plus Avastin had a
26-percent reduced risk of disease worsening or death (PFS) compared to
people treated with sunitinib (median PFS [mPFS]: 11.2 vs. 7.7 months;
HR=0.74; 95 percent CI 0.57, 0.96; p=0.02). Initial observations from
the co-primary endpoint of overall survival (OS) in the overall study
population (intention-to-treat, ITT) were encouraging, but are still
immature. Safety for the TECENTRIQ and Avastin combination appeared
consistent with the known safety profile of the individual medicines and
what was previously reported in the Phase II IMmotion150 study. No new
safety signals were identified with the combination. The rate of
treatment-related Grade 3-4 adverse events was lower with the TECENTRIQ
and Avastin combination (40 percent) than with sunitinib alone (54
percent) in all treated patients.

Observations of a pre-specified subgroup analysis of the TECENTRIQ and
Avastin combination indicated that, in people whose disease expressed
PD-L1, a numerical difference in PFS favoring TECENTRIQ was seen across
all patient risk factor groups (favorable, intermediate and poor)
compared to sunitinib. In addition, a pre-defined analysis of
patient-reported outcomes (PRO) revealed that the combination of
TECENTRIQ and Avastin markedly delayed the time to a worsening of
disease symptoms that interfere with day-to-day life compared to
sunitinib, (median time to deterioration: 11.3 vs. 4.3 months; HR=0.56;
95 percent CI: 0.46, 0.68) in the ITT population. Due to the study
design, pre-defined subgroup analyses and pre-defined PRO analyses were
not assessed for statistical significance and are descriptive only.

"This is the second positive Phase III study that includes TECENTRIQ and
Avastin as part of a treatment regimen, providing further evidence to
support the potential of this unique combination," said Sandra Horning,
M.D., chief medical officer and head of Global Product Development. "We
are encouraged that initial treatment with TECENTRIQ and Avastin
significantly reduced the risk of disease worsening or death in people
with advanced kidney cancer, while also providing more time before
disease symptoms interfered with day-to-day life compared with
sunitinib, a current standard of care. We look forward to discussing
these results with regulatory authorities worldwide."

The late-breaking IMmotion151 data will be presented at the 2018
Genitourinary Cancers Symposium on Saturday, Feb. 10 from 1:00-2:00 p.m.
Pacific Time (PT) (Abstract #578), and were highlighted as part of the
conference's official press program.

About the IMmotion151 study

IMmotion151 is a Phase III multicenter, randomized, open-label study to
evaluate the efficacy and safety of TECENTRIQ and Avastin versus
sunitinib in people with inoperable, locally advanced or metastatic
renal cell carcinoma (RCC) who have not received prior systemic active
or experimental therapy. It enrolled 915 people globally who were
randomized 1:1 to receive TECENTRIQ and Avastin, or sunitinib alone.

People in the TECENTRIQ and Avastin arm received TECENTRIQ at a fixed
dose of 1200 milligrams (mg) and Avastin at a dose of 15 milligrams per
kilogram (mg/kg) via intravenous (IV) infusion every 3 weeks until loss
of clinical benefit or unacceptable toxicity. People in the sunitinib
arm received sunitinib 50 mg orally, once daily for 4 weeks followed by
2 weeks rest until loss of clinical benefit or unacceptable toxicity.

The co-primary endpoints were PFS, as determined by the investigator
using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST
v1.1) in people whose tumors expressed PD-L1 (expression ≥1 percent on
immune cells [IC]), and OS in the overall study population
(intention-to-treat, ITT). PD-L1 expression was prospectively assessed
using an immunohistochemistry (IHC) test (SP142) developed by Roche
Tissue Diagnostics. Secondary endpoints included OS in people whose
tumors expressed PD-L1, PFS as determined by an Independent Review
Facility (IRF) according to RECIST v1.1, investigator-assessed objective
response rate (ORR) and median duration of response (mDOR), change from
baseline in symptom interference and symptom severity as determined by
M.D. Anderson Symptom Inventory (MDASI), and change from baseline in
health-related quality of life as determined by European Quality of Life
5-Dimension (EQ-5D) Scores.

Stratification factors included the Memorial Sloan-Kettering Cancer
Center (Motzer) prognostic scoring system, which predicts for OS based
upon an individual's baseline clinical and laboratory characteristics.
Depending on the presence of one or several of five variables (risk
factors), people are classified in one of the three risk groups:
"Favorable" with 0 risk factors, "Intermediate" with 1-2 risk factors
and "Poor" with ≥ 3 risk factors.

 
Phase III IMmotion151 Study Results: Investigator Assessed
Population  

PD-L1+ (programmed death-
ligand 1: Expression ≥1% on
IC)
n
= 362

 

ITT (intent-to-treat)
n = 915

 

Treatment Arm  

Sunitinib
n = 184

 

 

TECENTRIQ
& Avastin
n= 178

 

Sunitinib
n = 461

 

 

TECENTRIQ
& Avastin
n= 454

PFS   Co-Primary   Secondary

mPFS
(95% CI)

 

 

7.7 months
(6.8, 9.7)

 

 

11.2 months
(8.9, 15.0)

 

 

8.4 months
(7.5, 9.7)

 

 

11.2 months
(9.6, 13.3)

 

Stratified HR
(95% CI)

 

 

0.74
(0.57, 0.96)
P = 0.02

 

0.83
(0.70, 0.97)

 

ORR   Secondary   Secondary

ORR
(95% CI)

 

35%
(28, 42)

 

43%
(35, 50)

 

33%
(29, 38)

 

37%
(32, 41)

mDOR
(95% CI)

 

12.9 months
(9.8, NE)

 

NE
(12.4, NE)

 

14.2 months
(11.3, NE)

 

16.6 months
(15.4, NE)

Phase III IMmotion151 Study Results: IRF-Assesseda*

Population  

PD-L1+ (programmed death-
ligand 1: Expression ≥1% on
IC)
n
= 362

 

ITT (intent-to-treat)
n = 915

 

PFS   Secondary   Secondary

mPFS
(95% CI)

 

7.2 months
(6.1, 11.1)

 

8.9 months
(6.9, 12.5)

 

8.3 months
(7.0, 9.7)

 

9.6 months
(8.3, 11.5)

Stratified HR
(95% CI)

 

0.93
(0.72, 1.21)

 

0.88
(0.74, 1.04)

Initial observations from the co-primary endpoint of overall
survival:

Descriptive Only

Treatment  

TECENTRIQ
& Avastin

  Sunitinib  

TECENTRIQ
& Avastin

  Sunitinib
Population  

PD-L1+ (programmed death-
ligand 1: Expression ≥1% on
IC)
n
= 362

 

ITT (intent-to-treat)
n = 915

 

Median OS   Not reached  

23.3
(21.3, NR)

  Not reached

HR
(95% CI)

 

0.68
(0.46, 1.00)

 

0.81
(0.63, 1.03)

Event/patient ratio: PD-L1+, TECENTRIQ and Avastin, 25% and
sunitinib, 35%;
ITT, TECENTRIQ and Avastin, 27% and
sunitinib, 31%. Assessed by investigator;
minimum follow-up,
12 mo. Median of follow-up, 15 months.

NE, not estimable aData assessed by
independent review facility

*Difference in
IRF-assessed PFS HR driven by IC1/2/3 population (IRF-assessed PFS HR in
IC0 was 0.84 compared to 0.93 for Investigator-assessed PFS in IC0)
despite study participants being blinded to PD-L1 status.
Totality
of data support the Investigator assessment of PFS.
Preparations
for further analyses of IRF-assessed PFS are ongoing.

About renal cell carcinoma

According to the American Cancer Society, more than 63,300 people will
be diagnosed with kidney cancer in 2018. Renal cell carcinoma (RCC)
accounts for approximately 90 percent of all cases. RCC occurs when
abnormal cells develop in the tissue of the kidneys, specifically in the
small tubes (also known as tubules) where the blood is filtered.
Typically, RCC is a single tumor in one kidney but, in rare cases, there
can be multiple tumors, which can occur in one or both kidneys. Despite
recent progress in the field of kidney cancer, treatment options for
people with the disease remains limited.

About the TECENTRIQ (atezolizumab) and Avastin (bevacizumab)
combination

There is a strong scientific rationale to support further investigation
of TECENTRIQ plus Avastin in combination. We are investigating this
combination in a broad range of cancers, including advanced RCC.
Avastin, in addition to its anti-angiogenic effects, may further enhance
TECENTRIQ's ability to restore anti-cancer immunity, by inhibiting
VEGF-related immunosuppression, promoting T-cell tumor infiltration and
enabling priming and activation of T-cell responses against tumor
antigens.

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 Avastin® (bevacizumab)

Avastin is a prescription-only medicine that is a solution for
intravenous infusion. It is a biologic antibody designed to specifically
bind to a protein called vascular endothelial growth factor (VEGF) that
plays an important role throughout the lifecycle of the tumor to develop
and maintain blood vessels, a process known as angiogenesis. Avastin is
designed to interfere with the tumor blood supply by directly binding to
the VEGF protein to prevent interactions with receptors on blood vessel
cells. The tumor blood supply is thought to be critical to a tumor's
ability to grow and spread in the body (metastasize). Avastin is the
only currently available treatment for people with mRCC that directly
inhibits VEGF.

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 (advanced urothelial
      carcinoma), 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

Important Information About TECENTRIQ

TECENTRIQ can cause the immune system to attack normal organs and
tissues in many areas of the body and can affect the way they work.
These problems can sometimes become serious or life-threatening and can
lead to death.

Getting medical treatment right away may help keep these problems
from becoming more serious.
A healthcare provider may treat a
patient with corticosteroid or hormone replacement medicines. A
healthcare provider may delay or completely stop treatment with
TECENTRIQ if a patient has severe side effects.

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,
    or 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, 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 in the stools or dark, tarry, sticky stools, severe
    stomach area (abdomen) pain or tenderness
  • Hormone Gland Problems (especially the pituitary, thyroid, adrenal
    glands and pancreas) – 
    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, voice
  • gets deeper, urinating more often than usual, nausea or vomiting,
    stomach area (abdomen) pain
  • Nervous System Problems (neuropathy, meningitis, encephalitis) – Signs
    and symptoms of nervous system problems may include: severe muscle
    weakness, numbness or tingling in hands and feet, fever, confusion,
    changes in mood or behavior, extreme sensitivity to light, neck
    stiffness
  • Inflammation of the Eyes – Signs and symptoms may include
    blurry vision, double vision, other vision problems, eye pain or
    redness
  • Severe Infections – Signs and symptoms of infection may
    include: fever, cough, frequent urination, flu-like symptoms, pain
    when urinating
  • Severe Infusion Reactions – Signs and symptoms of infusion
    reactions may include: chills or shaking, itching or rash, flushing,
    shortness of breath or wheezing, dizziness, fever, feeling like
    passing out, back or neck pain, and swelling of the face or lips

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
    their 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
    • If patients are able to become pregnant, they should use an
      effective method of birth control during 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
  • shortness of breath
  • cough
  • nausea
  • muscle or bone pain
  • constipation

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.

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.

Avastin Indications:

  • Metastatic colorectal cancer (mCRC) for first- or second-line
    treatment in combination with intravenous 5-fluorouracil–based
    chemotherapy. It is also approved to treat mCRC for second-line
    treatment when used with fluoropyrimidine-based (combined with
    irinotecan or oxaliplatin) chemotherapy after cancer progresses
    following a first-line treatment that includes Avastin.
    • Avastin is not approved for use after the primary treatment of
      colon cancer that has not spread to other parts of the body.
  • Advanced nonsquamous non–small cell lung cancer (NSCLC) in
    combination with carboplatin and paclitaxel in people who have not
    received chemotherapy for their advanced disease.
  • Metastatic kidney cancer (mRCC) when used with interferon alfa.
  • Glioblastoma (GBM) in adult patients whose cancer has
    progressed after prior treatment (recurrent or rGBM).
  • Advanced cervical cancer (CC) in combination with paclitaxel
    and cisplatin or paclitaxel and topotecan is approved to treat
    persistent, recurrent, or metastatic cancer of the cervix.
  • Recurrent ovarian cancer (rOC). Avastin in combination with
    paclitaxel, pegylated liposomal doxorubicin or topotecan, is approved
    to treat platinum-resistant recurrent epithelial ovarian, fallopian
    tube or primary peritoneal cancer (prOC) in women who received no more
    than two prior chemotherapy treatments. Avastin, either in combination
    with carboplatin and paclitaxel or with carboplatin and gemcitabine,
    followed by Avastin alone, is approved for the treatment of patients
    with platinum-sensitive recurrent epithelial ovarian, fallopian tube,
    or primary peritoneal cancer (psOC).

Possible serious side effects

Everyone reacts differently to Avastin therapy. So it's important to
know what the side effects are. Although some people may have a
life-threatening side effect, most do not.
 Their doctor will stop
treatment if any serious side effects occur. Patients should talk to
their doctor if there are any signs of these side effects.

Most serious side effects (not common, but sometimes fatal):

  • GI perforation. A hole that
    develops in the stomach or intestine. Symptoms include pain in the
    abdomen, nausea, vomiting, constipation, or fever
  • Wounds that don't heal. A cut made
    during surgery can be slow to heal or may not fully heal. Avastin
    should not be used for at least 28 days before or after surgery and
    until surgical wounds are fully healed
  • Serious bleeding. This includes
    vomiting or coughing up blood; bleeding in the stomach, brain, or
    spinal cord; nosebleeds; and vaginal bleeding. If a patient has
    recently coughed up blood or had serious bleeding, they should be sure
    to tell their doctor

Other possible serious side effects

  • Abnormal passage in the body. This type of passage—known as a
    fistula—is an irregular connection from one part of the body to
    another and can sometimes be fatal
  • Severe high blood pressure. Blood pressure that severely spikes
    or shows signs of affecting the brain. Blood pressure should be
    monitored every 2 to 3 weeks while on Avastin and after stopping
    treatment
  • Kidney problems. These may be caused by too much protein in the
    urine and can sometimes be fatal
  • Infusion reactions. These were uncommon with the first dose
    (less than 3 percent of patients). 0.2 percent of patients had severe
    reactions. Infusion reactions include high blood pressure or severe
    high blood pressure that may lead to stroke, trouble breathing,
    decreased oxygen in red blood cells, a serious allergic reaction,
    chest pain, headache, tremors, and excessive sweating. The patient's
    doctor or nurse will monitor for signs of infusion reactions
  • Severe stroke or heart problems. These may include blood clots,
    mini-stroke, heart attack, chest pain, and the heart may become too
    weak to pump blood to other parts of the body (congestive heart
    failure). These can sometimes be fatal
  • Nervous system and vision problems. Signs include headache,
    seizure, high blood pressure, sluggishness, confusion, and blindness

Side effects seen most often

In clinical studies across different types of cancer, some patients
experienced the following side effects:

  • High blood pressure
  • Too much protein in the urine
  • Nosebleeds
  • Rectal bleeding
  • Back pain
  • Headache
  • Taste change
  • Dry skin
  • Inflammation of the skin
  • Inflammation of the nose
  • Watery eyes

Avastin is not for everyone

Patients should talk to their doctor if they are:

  • Undergoing surgery. Avastin should not be used for 28 days
    before or after surgery and until surgical wounds are fully healed
  • Pregnant or think they are pregnant. Data have shown that
    Avastin may harm a woman's unborn baby. Birth control should be used
    while patients are on Avastin. If Avastin is stopped, patients should
    keep using birth control for 6 months before trying to become pregnant
  • Planning to become pregnant. Taking Avastin could cause a
    woman's ovaries to stop working and may impair her ability to have
    children.
  • Breastfeeding. Breastfeeding while on Avastin may harm the baby
    and is therefore not recommended

Patients should talk with their doctor if they have any questions about
their condition or treatment.

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.

For full Prescribing Information on Avastin please visit http://www.avastin.com.

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 20 investigational medicines, 10 of
which are in clinical trials. 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

Founded more than 40 years ago, Genentech is a leading biotechnology
company that discovers, develops, manufactures and commercializes
medicines to treat patients with serious or 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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