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Genentech Presents Positive Results from Pivotal Study of Investigational Immunotherapy Atezolizumab in Specific Type of Advanced Bladder Cancer at 2015 European Cancer Congress

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SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced early results from a pivotal Phase II study, IMvigor 210, of the investigational cancer immunotherapy atezolizumab (anti-PDL1; MPDL3280A) in people with locally advanced or metastatic urothelial carcinoma (mUC). The study showed that atezolizumab shrank tumors (objective response rate, ORR) in 27 percent of people with mUC whose disease had medium and high levels of PD-L1 expression and worsened after initial treatment. Ninety-two percent of people who responded to atezolizumab continued to respond when the results were assessed. Median duration of response was not yet reached. Adverse events were consistent with those observed in previous studies.

"These results may represent the first major treatment advancement in advanced bladder cancer in nearly 30 years," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We are encouraged that responses to atezolizumab were ongoing in the large majority of people when the study results were assessed."

These data will be submitted to global health authorities and to the U.S. Food and Drug Administration (FDA) under atezolizumab's Breakthrough Therapy Designation for the treatment of people whose metastatic bladder cancer expresses PD-L1. This designation is designed to expedite the development and review of medicines intended to treat serious diseases that may demonstrate substantial improvements over existing therapies.

About the IMvigor 210 Study

These final results from Cohort 2 of this study (minimum of 24 weeks follow-up) will be presented in an oral session presentation by Jonathan E. Rosenberg, M.D., Memorial Sloan Kettering Cancer Center (Abstract #21LBA) on Sunday, Sept. 27, 10:40 a.m. Central European Time (CET).

Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 210)

IMvigor 210 is an open-label, multicenter, single-arm Phase II study that evaluated the safety and efficacy of atezolizumab in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1 consisted of people who had received no prior therapies for locally advanced or mUC, but who were ineligible for first-line cisplatin-based therapy; results for this Cohort are not yet mature. Cohort 2, for which results were announced today, included people whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen. People received a 1200-mg intravenous dose of atezolizumab on day one of 21-day cycles until progressive disease (Cohort 1) or loss of clinical benefit (Cohort 2).

The primary endpoint of the study was ORR. Secondary endpoints included duration of response (DoR), overall survival (OS), progression-free survival (PFS) and safety. People were selected by histology, prior lines of therapy and PD-L1 expression on tumor-infiltrating immune cells (ICs) using an investigational immunohistochemistry (IHC) test that is being developed by Roche Diagnostics.

IMvigor 210 Cohort 2 Study Results
Study Group

IC 2/3 (Medium and
High)

IC 1/2/3 (Any
Expression)

Intent-To-Treat
(ITT; All Patients)

Number of Patients 100 208 311
Objective Response Rate* (Co-Primary Endpoints)

IRF-assessed ORR per
RECIST v1.1
(95% CI)

27%

(19%, 37%)

18%

(13%, 24%)

15%

(11%, 20%)

P value p<0.0001 p=0.0004 p=0.0058

Investigator-assessed
ORR per modified
RECIST (95% CI)

26%

(18%, 36%)

21%

(15%, 27%)

18%

(14%, 23%)

P value p<0.0001 p<0.0001 p<0.0001
Duration of Response (IRF-Assessed; RECIST v1.1) (Secondary Endpoint)

Median DoR (months)
(95% CI)

Not Reached

(6.0, NE)

Progression-Free Survival (IRF-Assessed; RECIST v1.1) (Secondary Endpoint)

Median PFS (months)
(95% CI)

2.1

(2.1, 4.1)

2.1

(2.1, 2.1)

2.1

(2.1, 2.1)

Overall Survival (Secondary Endpoint)

Median OS (months)
(95% CI)

NR 8.0

(6.7, NE)

7.9

(6.7, NE)

*ORR was assessed by central review (RECIST v1.1) and by investigators using modified RECIST (co-primary endpoints); CI: confidence interval; NR: not reached; NE: not estimable

Safety was assessed in 311 people and adverse events were consistent with those observed in previous studies and there were no treatment-related deaths. Fifteen percent of people experienced Grade 3-4 treatment related adverse events and four percent of people experienced a Grade 3-4, immune related adverse event. The most common Grade 3-4 treatment related adverse events were fatigue (2 percent), decreased appetite, fever (pyrexia), pain (arthralgia), shortness of breath (dyspnea), anemia, enzymes in the blood (ALT increase), inflammation of the lung wall (pneumonitis), hypertension and hypotension (all 1 percent).

In addition to IMvigor 210, Genentech has an ongoing randomized Phase III study, IMvigor 211, comparing atezolizumab with standard-of-care chemotherapy in people who have relapsed mUC that worsened after initial treatment. All studies include the evaluation of a companion test developed by Roche Diagnostics to determine PD-L1 status.

About Metastatic Urothelial Carcinoma

Urothelial carcinoma accounts for 90 percent of all bladder cancers. According to the American Cancer Society (ACS), it is estimated that more than 74,000 Americans will be diagnosed with bladder cancer in 2015, and approximately 15,000 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 15 percent of people with advanced bladder cancer (stage IV) will live for five years, compared to 88 percent when diagnosed during stage I. Men are about three to four times more likely to get bladder cancer during their lifetime than women.

About Atezolizumab

Atezolizumab (also known as MPDL3280A; anti-PDL1) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.

All studies of atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both tumor cells and infiltrating immune cells. The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with atezolizumab alone, and to determine which people may benefit most from a combination of atezolizumab and another medicine. There are 11 ongoing or planned Phase III studies of atezolizumab across certain kinds of lung, kidney, breast and bladder cancer.

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, seven 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/immunotherapy.

About Genentech

Founded more than 35 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.

Genentech
Media Contact:
Holli Kolkey, 650-922-1269
Advocacy Contact:
Sonali Chopra, 650-467-0842
Investor Contacts:
Stefan Foser, 650-467-2016
Karl Mahler, 011 41 61 687 8503

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