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Genentech Presents Positive Phase III Results for Tecentriq (Atezolizumab) in Combination With Platinum-based Chemotherapy in People With Previously Untreated Advanced Bladder Cancer

September 30, 2019 Off By BusinessWire

– IMvigor130 is the first positive Phase III study of a cancer immunotherapy combination in people with previously untreated advanced bladder cancer –

– Tecentriq combination reduced the risk of disease worsening or death (progression-free survival) compared with chemotherapy alone –

– Data will be presented today at the 2019 European Society for Medical Oncology (ESMO) Congress –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today presented positive results from the Phase III IMvigor130 study evaluating Tecentriq^® (atezolizumab) plus platinum-based chemotherapy versus chemotherapy alone for the first-line (initial) treatment of people with previously untreated locally advanced or metastatic urothelial carcinoma (mUC) eligible and ineligible for cisplatin chemotherapy. In the study, Tecentriq plus chemotherapy showed a statistically significant improvement in progression-free survival (PFS) compared with platinum-based chemotherapy alone (median PFS=8.2 versus 6.3 months; hazard ratio [HR]=0.82, 95% CI: 0.70-0.96; p=0.007). Encouraging overall survival (OS) results were observed for Tecentriq plus chemotherapy compared with chemotherapy alone in the intention-to-treat (ITT) population, however these data did not reach statistical significance at this interim analysis (median OS=16.0 versus 13.4 months; HR=0.83, 95% CI: 0.69-1.00). Safety in the Tecentriq plus chemotherapy arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.

“We are pleased with these positive results from the IMvigor130 study, which show Tecentriq plus chemotherapy may provide a meaningful benefit for people newly diagnosed with advanced bladder cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “There remains a high unmet need for people with advanced bladder cancer, where chemotherapy alone is the current standard of care. These results reinforce the role of immunotherapy in treating this aggressive disease.”

Additional data from the Tecentriq monotherapy arm were also presented in the ITT population and people with different levels of PD-L1 expression. Encouraging OS results were observed with Tecentriq monotherapy in people with high PD-L1 expression (IC2/3), however these data were not formally tested per the hierarchical design of the trial. Follow-up will continue until the next analysis.

These data will be presented today at the European Society for Medical Oncology (ESMO) 2019 Congress Presidential Symposium from 5:53 – 6:05 p.m. CEST (Abstract LBA14) and were featured in the official ESMO press program.

Tecentriq was the first cancer immunotherapy approved in advanced bladder cancer. Tecentriq has accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adults with locally advanced or mUC, including those who are not eligible for cisplatin-containing chemotherapy and whose tumors express high levels of PD-L1 (PD-L1–stained tumor-infiltrating immune cells covering ≥5% of the tumor area) as determined by an FDA-approved test or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. The accelerated approval also includes the treatment of adults with locally advanced or mUC whose disease had progressed during or following platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). These accelerated approvals are based on tumor response rate and durability of response. Continued approval in these types of bladder cancer may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Currently, there are four ongoing Phase III studies evaluating Tecentriq alone and in combination with other medicines in early and advanced bladder 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 IMvigor130 study

IMvigor130 is a multicenter, partially blinded, randomized Phase III study, evaluating the efficacy and safety of Tecentriq in combination with chemotherapy or alone versus chemotherapy alone for people with mUC who have not received prior systemic therapy for metastatic disease. It enrolled 1,213 people who received:

Tecentriq plus platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin), or
Tecentriq, or
Platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin) plus placebo (control arm).

In the Tecentriq combination arm, the co-primary endpoints are OS and PFS as assessed by investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The secondary endpoints are objective response rate and duration of response, as assessed by investigator using RECIST v1.1, and independent review facility-assessed PFS.

A summary of the key study results is included below:

	Tecentriq + platinum-based chemotherapy n=451	Placebo + platinum-based chemotherapy n=400
PFS (co-primary endpoint)
Median PFS (months) (95% CI)	8.2 (6.5, 8.3)	6.3 (6.2, 7.0)
HR (95% CI)	0.82 (0.70, 0.96)
P value	P=0.007
OS (co-primary endpoint)
Median OS (months)	16.0	13.4
(95% CI)	(13.9, 18.9)	(12.0, 15.2)
HR (95% CI)	0.83 (0.69, 1.00)*
ORR (secondary endpoint)
Responders (%)	212 (47.4%)		174 (43.8%)
95% CI	(42.7%, 52.2%)		(38.9%, 48.9%)
Complete response %	56 (12.5%)		27 (6.8%)
*The OS result did not cross the pre-specified efficacy boundary for statistical significance. Follow-up will continue until the next interim analysis.

Safety for the Tecentriq plus chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. There appeared to be no worsening of tolerability with the addition of Tecentriq to chemotherapy compared with chemotherapy alone. All cause Grade 3-4 adverse events (AEs) were reported in 85% of people receiving Tecentriq plus chemotherapy compared with 86% of people receiving chemotherapy alone. Treatment-related Grade 3-4 AEs were reported in 83% of people receiving Tecentriq plus chemotherapy compared with 81% of people receiving chemotherapy alone. Any grade AEs leading to any treatment discontinuation of Tecentriq or placebo were observed in 11% and 7% of people in the combination arm compared with the chemotherapy arm respectively.

About bladder cancer

According to the American Cancer Society (ACS), it is estimated that more than 80,000 Americans will be diagnosed with bladder cancer in 2019, and about 11% of new diagnoses are made when bladder cancer is in advanced stages. There is a dramatic difference in survival rates between early and advanced bladder cancer. The ACS estimates that approximately 90% of people will live five or more years when diagnosed with the earliest stage of the disease, compared to 40% when diagnosed in advanced stages (stage III-IV) of the disease. Men are about three to four times more likely to get bladder cancer during their lifetime than women.

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 bladder and urinary tract cancer called urothelial carcinoma. Tecentriq may be used when your bladder cancer:

has spread or cannot be removed by surgery, and if you have any one of the following conditions:
- you are not able to take chemotherapy that contains a medicine called cisplatin, and your doctor has tested your cancer and found high levels of a specific protein on your cancer called programmed death-ligand 1 (PD-L1), or
- you are not able to take chemotherapy that contains any platinum regardless of the levels of “PD-L1” status, 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. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

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 your skin or the whites of your 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 your 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 your 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
constipation
cough
shortness of breath
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

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.