Friday, Feb 17, 2017

Phase II Study Supports Potential for Genentech’s Tecentriq® (Atezolizumab) Plus Avastin® (Bevacizumab) for People with Locally Advanced or Metastatic Renal Cell Carcinoma

Proof-of-concept study in first-line mRCC (a type of kidney cancer) shows that TECENTRIQ and Avastin can be combined with a manageable safety profile

Study results also showed encouraging efficacy compared to sunitinib in those people whose disease expressed the PD-L1 (programmed death-ligand 1) protein

Genentech is evaluating TECENTRIQ plus Avastin in a Phase III study (IMmotion151) in people with previously untreated, locally advanced or metastatic RCC

South San Francisco, CA -- February 17, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced encouraging results from the Phase II IMmotion150 study that compared TECENTRIQ^® (atezolizumab) plus Avastin^® (bevacizumab) and TECENTRIQ monotherapy to sunitinib alone in people with previously untreated, locally advanced or metastatic renal cell carcinoma (mRCC). These results were presented at the 2017 Genitourinary Cancers Symposium taking place from February 16-18 in Orlando, Fla. IMmotion150 is the first randomized clinical trial to evaluate the combination of TECENTRIQ and Avastin in mRCC. The study was designed to inform further clinical development of this combination, and these study results reinforce the potential of this combination in this setting.

The study showed that people whose disease expressed PD-L1 (programmed death-ligand 1) and were treated with TECENTRIQ plus Avastin had a 36 percent reduction in the risk of their disease worsening or death compared to people treated with sunitinib alone (median progression-free survival [mPFS]: 14.7 vs. 7.8 months; HR = 0.64; 95% CI 0.38, 1.08). No PFS advantage was observed compared to sunitinib in the intention-to-treat (ITT) population (mPFS: 11.7 vs. 8.4 months; HR = 1.00; 95% CI 0.69, 1.45). Median duration of response (DoR) has not yet been reached after 20.7 months of follow-up across treatment arms. Adverse events in the TECENTRIQ plus Avastin arm were consistent with those observed in previous studies of each medicine.

“These Phase II results support the scientific rationale for potentially combining TECENTRIQ and Avastin in people with this type of kidney cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “There is a significant need for new treatment options for people living with advanced RCC, a disease where currently only about one in 10 people are alive beyond five years following diagnosis.”

Genentech is also evaluating TECENTRIQ plus Avastin compared to sunitinib in a Phase III study (IMmotion151; NCT02420821) in people with previously untreated, locally advanced or metastatic RCC. A study of TECENTRIQ as adjuvant treatment for RCC began enrolling earlier this year.

About the IMmotion150 study

IMmotion150 is a global, multicenter, open-label, randomized Phase II study that was designed to evaluate the efficacy and safety of TECENTRIQ plus Avastin (Arm A), TECENTRIQ alone (Arm B) or sunitinib alone (Arm C) in 305 people with previously untreated, locally advanced or metastatic RCC. People in Arm A received TECENTRIQ administered intravenously at 1200 milligrams (mg) every 3 weeks (6-week cycles) plus Avastin intravenously at 15 mg until disease progression or lack of clinical benefit. People in Arm B received TECENTRIQ alone (until disease progression or lack of clinical benefit), and people in Arm C received sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks rest until disease progression.

The co-primary endpoints were PFS per RECIST v.1.1 via Independent Review Facility (IRF) assessment in all randomized patients (ITT population) and in the PD-L1- selected (IC1/2/3) subgroup. PD-L1 expression was assessed on tumor-infiltrating immune cells (IC) with an investigational immunohistochemistry (IHC) test based on the SP142 antibody being developed by Roche Tissue Diagnostics. Secondary endpoints included IRF-assessed overall response rate (ORR) and duration of response (DoR), investigator-assessed PFS, ORR, DoR and safety, and overall survival (OS). A summary of the efficacy data from Arms A, B and C of the IMmotion150 study is included below.

IMmotion150 primary analysis efficacy results by IRF

	IC1/2/3 subgroup (PD-L1 expression on >1% IC)			ITT population
Treatment	TECENTRIQ + Avastin (n=50)	sunitinib (n=60)	TECENTRIQ (n=54)	TECENTRIQ + Avastin (n=101)	sunitinib (n=101)	TECENTRIQ (n=103)
Median PFS, months	14.7	7.8	5.5	11.7	8.4	6.1
Stratified HR* (95% CI)	0.64 (0.38, 1.08)	-	1.03 (0.63, 1.67)	1.00 (0.69, 1.45)	-	1.19 (0.82, 1.71)
Stratified log-rank p value*	0.095	-	0.917	0.982	-	0.358
Overall Response Rate (ORR)	46%	27%	28%	32%	29%	25%
Complete Responses(CR)	12%	7%	15%	7%	5%	11%
Duration of Response (DoR)	N.E	N.E	N.E	N.E	N.E	N.E
CI, confidence interval; HR, hazard ratio *Relative to sunitinib p-values provided for descriptive purposes only and not adjusted for multiple comparisons

IMmotion150 was designed with planned crossover. Over three-quarters (78 percent) of people receiving sunitinib (Arm C) who progressed subsequently received TECENTRIQ plus Avastin (Arm A). OS results were immature at time of analysis with only 35 percent of events having occurred.

Safety in the TECENTRIQ plus Avastin arm appeared consistent with the known safety profile of the individual medicines. No new safety signals were identified. Frequency of all-grade treatment-related adverse events (AEs) was similar between arms. The most common AEs occurring in more than 20 percent of people receiving TECENTRIQ plus Avastin and with a greater than 5 percent increase when compared to sunitinib included: arthralgia (38 percent), proteinuria (36 percent), epistaxis (28 percent) and pruritus (22 percent). Frequency of grade 3-4 AEs regardless of relationship to treatment were similar between people treated with TECENTRIQ plus Avastin (63 percent) and sunitinib (69 percent). Treatment-related grade 3-4 events were reported in 40 percent of people treated with TECENTRIQ plus Avastin and in 57 percent of people treated with sunitinib. One person who was treated with TECENTRIQ plus Avastin experienced intracranial hemorrhage that led to death. Fifteen of 101 people (15 percent) treated with TECENTRIQ plus Avastin discontinued treatment for adverse events.

About renal cell carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer and forms when abnormal cells develop in the small tubes (known as renal tubules) in the kidneys. In 2017, about 64,000 people will be diagnosed with kidney cancer in the United States and more than 14,000 will die from the disease. The disease is more prevalent in men and people aged 55-74 years. Currently there is a significant need for more effective treatments with only about one in 10 people alive five years post-diagnosis.

About TECENTRIQ

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 activation of T cells. TECENTRIQ may also affect normal cells.

About Avastin

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).

TECENTRIQ U.S. Indications

TECENTRIQ is a prescription medicine used to treat:

• A type of bladder 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 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 your immune system to attack normal organs and tissues in many areas of your 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. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may delay or completely stop treatment with TECENTRIQ if you have 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, and 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 your face or lips

Before you receive TECENTRIQ, tell your healthcare provider about all your medical conditions, including if you:

• 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 your 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 your unborn baby
  • If you are able to become pregnant, 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 your 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 previously-treated people with urothelial carcinoma include:

• feeling tired
• decreased appetite
• nausea
• urinary tract infection
• fever
• constipation

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
• constipation

TECENTRIQ may cause fertility problems in females, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of TECENTRIQ. Ask your healthcare provider or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-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 TECENTRIQ full Prescribing Information for additional Important Safety Information.

Avastin Indications

• Avastin is indicated for the first or second line treatment of patients with metastatic colorectal cancer in combination with intravenous 5 fluorouracil–based chemotherapy.
• Avastin in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy is indicated for the second line treatment of patients with metastatic colorectal cancer who have progressed on a first line Avastin-containing regimen. Avastin is not indicated for adjuvant treatment of colon cancer.
• Avastin in combination with carboplatin and paclitaxel chemotherapy is indicated for first line treatment of patients with unresectable, locally advanced, recurrent or metastatic nonsquamous, non-small cell lung cancer.
• Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.
• Avastin in combination with paclitaxel and cisplatin or paclitaxel and topotecan is indicated for the treatment of persistent, recurrent or metastatic carcinoma of the cervix.
• 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).

BOXED WARNINGS and Additional Important Safety Information 


People receiving Avastin may experience side effects. In clinical trials, some people treated with Avastin experienced serious and sometimes fatal side effects, including:

Gastrointestinal (GI) perforation:

• Treatment with Avastin can result in the development of a serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine, or large intestine.
• In clinical trials, this event occurred in more people who received Avastin than in the comparison group (up to 3.2%).
• In some cases, GI perforation resulted in fatality. Avastin therapy should be permanently stopped if GI perforation occurs. 


Surgery and wound healing problems:

• Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases, this event resulted in fatality.
• Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. In a controlled clinical trial, in patients with metastatic colorectal cancer who had surgery during the course of treatment, the incidence of wound healing complications, including serious and fatal complications, was 15% for patients who received Avastin and 4% for patients who did not receive Avastin.
• Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of wound healing problems following surgery has not been determined.
• Treatment with Avastin should be stopped at least 28 days before voluntary surgery and in people with wound healing problems following surgery that require medical treatment. Treatment with Avastin should be stopped in patients with slow or incomplete wound healing.

Severe bleeding:

• Treatment with Avastin can result in serious or fatal bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds and vaginal bleeding. These events occurred up to five times more often in people who received Avastin compared to patients who received only chemotherapy.
• Across cancer types, 0.4% to 6.9% of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin. Treatment with Avastin should be permanently stopped if serious bleeding occurs. 


Additional serious adverse events

In clinical trials for different cancer types, there were additional serious and sometimes fatal side effects that occurred in more people who received Avastin than in those in the comparison group.

• The formation of an abnormal passage in the body (GI and non-GI fistula formation) was seen in up to 2% of people in metastatic colorectal cancer and ovarian cancer patients. In a study of patients with cervical cancer, formation of an abnormal passage between the vagina and GI tract was seen in 8.3% of people.
• Severe to life-threatening stroke or heart problems were seen in 2.6% of people.
• Too much protein in the urine that led to kidney problems was seen in ≤1% of people.
• Additional serious side effects that occurred in more people who received Avastin than those in the comparison group included
  • Severe to life-threatening blood clots (VTE), up to 10.6%

  • Severe to life-threatening high blood pressure, which was seen in 5% to 18% of people
  • Nervous system and vision disturbances (Posterior Reversible Encephalopathy Syndrome), which was seen in less than 0.5% of people.
  • Infusion reactions with the first dose of Avastin were uncommon and occurred in less than 3% of people, and severe reactions occurred in 0.2% of people.
• Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children. Avastin should not be used in ovarian cancer patients who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction. 


Patients who are pregnant, think they are pregnant, or thinking of becoming pregnant should talk with their doctor about the potential risk of loss of the pregnancy or the potential risk of Avastin to the fetus during and following Avastin therapy, and the need to continue an effective birth control method for six months following the last dose of Avastin. Avastin can cause fertility issues for women.

Women should be advised that breastfeeding while on Avastin may harm the baby and is therefore not recommended.

Common side effects that occurred in more than 10% of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain and inflammation of the skin (exfoliative dermatitis).

Across all trials, treatment with Avastin was permanently stopped in 8.4% to 21% of people because of side effects.

In the metastatic kidney cancer trial, the most common severe to fatal side effects that increased by 2% or more in people who received Avastin vs those in the comparison group included tiredness (13% vs 8%), weakness (10% vs 7%), too much protein in the urine (7% vs 0%), high blood pressure (6% vs 1%), and severe bleeding (3% vs 0.3%).

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 and Boxed WARNINGS 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 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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