Genentech's Investigational Immunotherapy Atezolizumab Shrank Tumors in Pivotal Study

Genentech, a member of the Roche Group recently announced that in the IMvigor 210 study, the investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PDL1) shrank tumors (objective response rate; ORR; the primary endpoint of this Phase II study) in people with locally advanced or metastatic urothelial bladder cancer (UBC) who had progressed on initial treatment (second-line or later). High amounts of PD-L1 (Programmed Death Ligand-1) expression by a person’s cancer correlated with increased response to the medicine. Adverse events were consistent with what has been previously observed for atezolizumab.

“We plan to present results at an upcoming medical meeting, and will discuss next steps with health authorities to bring a new treatment option to patients as soon as possible.”
“We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study because minimal progress has been made in advanced bladder cancer for nearly 30 years,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We plan to present results at an upcoming medical meeting, and will discuss next steps with health authorities to bring a new treatment option to patients as soon as possible.”

Last year, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for atezolizumab in people whose metastatic bladder cancer expressed PD-L1. This designation is designed to expedite the development and review of medicines intended to treat serious diseases.

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 metastatic UBC, 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 metastatic UBC, 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 progressed during or following previous treatment with a platinum-based chemotherapy regimen (second-line or later). People received a 1200-milligram 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. PD-L1 expression was assessed using an investigational immunohistochemistry (IHC) test being developed by Roche Diagnostics.

In addition to the IMvigor 210, Genentech has an ongoing randomized Phase III study, IMvigor 211, comparing atezolizumab with standard-of-care chemotherapy in people who have relapsed UBC, and a planned Phase III study, IMvigor 010, that will evaluate atezolizumab compared with observation in people with early-stage muscle-invasive bladder cancer who are selected for PD-L1 expression and are at risk for recurrence (adjuvant). All studies include the evaluation of a companion test developed by Roche Diagnostic to determine PD-L1 status.

Metastatic urothelial bladder cancer is associated with a poor prognosis and limited treatment options. 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.

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.

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.

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.