• First Phase III Data on Obinutuzumab (GA101) in one of the Most Commonly Diagnosed Blood Cancers;
• Early Stage Data on Investigational Anti-PDL1 Immunotherapy;
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that important new data from clinical trials of several investigational and approved cancer medicines will be presented at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 31 to June 4, 2013, in Chicago. At the meeting, Genentech medicines will be highlighted in more than 275 abstracts, of which approximately one third were chosen for oral presentations. The collection of data at ASCO represents Genentech's breadth of research and includes:
• Next-generation biologics, such as glycoengineered antibodies and antibody-drug conjugates;
• Immunotherapies designed to work with the body's immune system;
• Medicines designed to interfere with cancer cell growth and survival mechanisms;
• Efforts to map the precise characteristics of tumor cells, helping to determine which patients may respond to an experimental medicine.
"We need treatments that attack cancer cells in a variety of ways to continue to make a difference to the lives of people facing this disease," said Hal Barron, M.D., chief medical officer and head, Global Product Development. "From harnessing a person's immune system to delivering chemotherapy directly to a cancer cell, we believe the new data from our pipeline presented at ASCO have the potential to markedly change how cancer is treated."
Full session details of the 2013 Annual Meeting can be found through the ASCO iPlanner: iplanner.asco.org/am2013.
Key Genentech Meeting Highlights Include:
GA101: Unique Investigational Anti-CD20 Antibody
The Phase III study CLL11, which is being conducted in close collaboration with the German CLL Study Group (GCLLSG), compared the combination of either GA101 or Rituxan® (rituximab) and standard chemotherapy (chlorambucil) to chlorambucil alone. The study included people with previously untreated chronic lymphocytic leukemia (CLL), one of the most common forms of blood cancer, who were elderly and are often not able to tolerate existing standard options for CLL.
GA101 (RG7159, obinutuzumab) is the first investigational glycoengineered Type II anti-CD20 medicine, which means specific sugar molecules in GA101 were modified (using GlycoMAb® technology) to change its interaction with the body's immune cells with the goal of helping the immune system remove cancer cells from the body. In addition, as a Type II anti-CD20 antibody, GA101 binds to CD20 with the aim of killing cancerous cells directly.
Anti-PDL1 antibody MPDL3280A (RG7446) is an investigational medicine designed to make cancer cells more vulnerable to the body's own immune system by interfering with a protein called PD-L1. Several early stage studies of MPDL3280A in various cancer types will be presented, including data on potential biomarkers. These data will also be highlighted as part of ASCO's official press program on May 15, 2013.
ADCs: Antibody-Drug Conjugates
ADCs are designed to combine the specificity of antibodies with chemotherapy by seeking and attaching to certain types of cancer cells to deliver chemotherapy directly to them. The goal of ADCs is to reduce the effects of chemotherapy on healthy cells. Genentech has nine ADCs in clinical trials. Early stage clinical data will be presented on investigational ADCs for lung, ovarian and prostate cancer: RG7599 (anti-NaPi2b) and RG7450 (anti-STEAP1).
GDC-0199: Targeting Cancer Cell Survival
BCL-2 inhibitor GDC-0199 (RG7601, ABT-199) is being studied in CLL and non-Hodgkin¿s lymphoma (NHL), and is designed to work by interfering with the process by which some cancer cells survive, thereby promoting a natural death process known as apoptosis. Early data will be presented on GDC-0199 in CLL and NHL.
Oncology Pipeline with Extensive Biomarker and Companion Diagnostic Program
The Roche/Genentech oncology pipeline includes 40 investigational cancer medicines being studied in 600 clinical trials across a dozen types of cancer.
The combination of Roche/Genentech medicines and Roche diagnostics enables the company to research a broad spectrum of tumor biomarkers, each accompanied by a clinical diagnostic test. Every oncology pipeline medicine includes a corresponding biomarker program that can help identify people who may be appropriate to receive a specific medicine. Currently, three out of four investigational medicines in the oncology pipeline are being studied with a companion diagnostic test.
Avastin: Interfering with the Tumor Blood Supply
Avastin® (bevacizumab) is a medicine designed to specifically bind to the vascular endothelial growth factor (VEGF) protein. Avastin may block the tumor's ability to communicate with nearby blood vessels and may prevent the tumor from connecting to the blood supply.
Results from more than 70 studies of Avastin are being presented at ASCO across several different cancers, including National Cancer Institute-sponsored Phase III studies of cervical cancer and glioblastoma (GBM) and a Genentech-sponsored Phase III study in GBM. These studies are an example of Genentech's continued commitment to research on anti-angiogenesis across different tumor types.
List of Studies Referred to Above:
• Abstract #7004: Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab ® plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial. Oral presentation, Tuesday, June 4, 9:15 - 9:30 AM CDT, in E354b
• Abstract #3000: A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. ASCO press briefing May 15, 2013. Oral presentation, Monday, June 3, 3:00 - 3:15 PM CDT in S406
• Abstract #3001: Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study. Oral presentation, Monday, June 3, 3:15 - 3:30 PM CDT in S406
• Abstract #3622: Clinical activity, safety and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic CRC, gastric cancer (GC), SCCHN or other tumors. Poster session, Sunday, June 2, 8:00 - 11:45 AM CDT in S Hall A2
• Abstract #8008: Clinical activity, safety and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Oral presentation, Monday, June 3, 5:30 - 5:45 PM CDT in E Hall D2
• Abstract #9010: Clinical activity, safety and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM). Symposium session, Sunday, June 2, 10:15 - 10:30 AM CDT in E Arie Crown Theater
• Abstract #4505: Clinical activity, safety and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with metastatic renal cell carcinoma (mRCC). Oral presentation, Saturday, June 1, 2:45 - 3:00 PM CDT in E Arie Crown Theater
• Abstract #2507: A phase I study of the safety and pharmacokinetics of DNIB0600A, an anti-NaPi2b antibody-drug-conjugate (ADC), in patients with non-small cell lung cancer (NSCLC) and platinum-resistant ovarian cancer (OC). Oral presentation, Sunday, June 2, 10:15 - 10:30 AM CDT in S406
• Abstract #5020: A phase I study of the safety and pharmacokinetics of DSTP3086S, an anti-STEAP1 antibody-drug conjugate (ADC), in patients (pts) with metastatic castration-resistant prostate cancer (CRPC). Poster session, Saturday, June 1, 8:00 AM - 12:00 PM CDT in E450a
Cell Communications / GDC-0199
• Abstract #7018: Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Poster session, Saturday, June 1, 8:00 AM - 12:00 PM CDT in S405
• Abstract #8520: Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Symposium session, Monday, June 3, 12:30 - 12:45 PM CDT in E354a
• Abstract #3: Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group. Plenary session, Sunday, June 2, 2:50 - 3:05 PM CDT in N Hall B1
• Abstract #2005: Progression-free survival (PFS) and health-related quality of life (HRQoL) in AVAglio, a phase III study of bevacizumab (Bv), temozolomide (T) and radiotherapy (RT) in newly diagnosed glioblastoma (GBM). Oral presentation, Saturday, June 1, 4:30 - 4:45 PM CDT in E253
• Abstract #2002: Tumor response based on adapted Macdonald criteria and assessment of pseudoprogression (PsPD) in the phase III AVAglio trial of bevacizumab (Bv) plus temozolomide (T) plus radiotherapy (RT) in newly diagnosed glioblastoma (GBM). Oral presentation, Saturday, June 1, 3:30 - 3:45 PM CDT in E253
• Abstract #1: RTOG 0825: phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). Plenary session, Sunday, June 2, 1:50 - 2:05 PM CDT in N Hall B1
The ADCs anti-NaPi2b and anti-STEAP1 are being developed utilizing Seattle Genetics' ADC technology.
GDC-0199 is being developed in collaboration with AbbVie.
Rituxan is a therapeutic antibody that binds to a specific protein called CD20 found on the surface of cancerous and normal B cells. In CLL, NHL and rheumatoid arthritis (RA), Rituxan works with the body's own immune system to eliminate marked CD20-positive B cells. Stem cells (those cells that give rise to B cells) in bone marrow do not have the CD20 protein. B cells usually regenerate after Rituxan treatment and return to normal levels in about 12 months for most patients.
Rituxan, discovered by Biogen Idec, first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent. It was approved in the European Union under the trade name MabThera in June 1998.
Rituxan (rituximab) is indicated for the treatment of patients with:
• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as single-agent maintenance therapy
• Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
• Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)
Rituxan is not recommended for use in patients with severe, active infections.
Important Safety Information Rituxan can cause serious side effects that can lead to death, including: infusion reactions, tumor lysis syndrome (kidney failure due to fast breakdown of cancer cells), severe skin and mouth reactions, and progressive multifocal leukoencephalopathy (a rare, serious brain infection).
Rituxan has also been associated with serious and life-threatening side effects, including: the return of active hepatitis B virus infection with sudden and serious liver problems including liver failure, and death, other serious infections that can lead to death, heart problems, kidney problems, and stomach and serious bowel problems including blockage and tears in the bowel, that can sometimes lead to death.
The most common side effects of Rituxan seen in patients with NHL were infusion reactions, fever, chills, low white blood cells, infections, body aches, and tiredness. The most common side effects of Rituxan in patients with CLL were infusion reactions and low white blood cells. Patients should talk to their doctor about their medical history before starting treatment with Rituxan.
Patients should tell their doctor about any side effect that bothers them or that does not go away. These are not all of the possible side effects with Rituxan.
Report side effects to the FDA at (800) FDA-1088 or fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555.
Patients should read the Rituxan Full Prescribing Information including Boxed WARNINGS, and the Medication Guide at rituxan.com/.
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 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
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 (2.4 percent to 0.3 percent). 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 percent for patients who received Avastin and four percent 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, 1.2 percent to 4.6 percent 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.
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 from parts of the body to another part (non-GI fistula formation) was seen in 0.3 percent or less of people. Severe to life threatening stroke or heart problems were seen in 2.6 percent of people. Too much protein in the urine that led to kidney problems was seen in less than one percent 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 high blood pressure, which was seen in five percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1 percent of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than three percent of people, and severe reactions occurred in 0.2 percent of people. Avastin can cause fertility issues for women. Avastin could cause a woman¿s ovaries to stop working and may impair her ability to have children.
Common side effects that occurred in more than 10 percent 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 percent to 21 percent of people because of side effects.
Patients who 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 at least six months following the last dose of Avastin.
Women should be advised to discontinue nursing or discontinue treatment with Avastin, taking into account the importance of Avastin to the mother.
Report side effects to the FDA at (800) FDA-1088 or fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555.
For full Prescribing Information and Boxed WARNINGS on Avastin, please visit avastin.com/.
Founded more than 30 years ago, Genentech (gene.com) 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.