Wednesday, May 13, 2015
South San Francisco, CA -- May 13, 2015 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced interim results from a global, randomized Phase II study (POPLAR) in people with previously treated non-small cell lung cancer (NSCLC). The study showed the investigational cancer immunotherapy MPDL3280A (anti-PDL1) reduced the risk of death by half (53%) (overall survival [OS]; hazard ratio [HR]=0.47) in people whose cancer expressed the highest levels of PD-L1 (programmed death ligand-1) compared with docetaxel chemotherapy. An improvement in survival was also observed in people who had medium and high (HR=0.56) or any level of PD-L1 expression (HR=0.63), as characterized by a test being developed by Roche. MPDL3280A was generally well tolerated and adverse events were consistent with what has been previously reported for MPDL3280A in NSCLC. Updated results will be presented in an oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).
In our study of MPDL3280A in previously treated lung cancer, the amount of PD-L1 expressed by a person’s cancer correlated with improvement in survival,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “The goal of PD-L1 as a biomarker is to identify people most likely to experience improved overall survival with MPDL3280A alone, and which people may be appropriate candidates for a combination of medicines.”
In February 2015, MPDL3280A received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of people whose NSCLC expresses PD-L1 and who progressed during or after standard treatments (e.g., platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). Genentech is discussing the interim data from POPLAR with the FDA as part of Breakthrough Therapy Designation in lung cancer. Genentech currently has three Phase II and six Phase III studies of MPDL3280A ongoing in various kinds of lung cancer.
About the POPLAR Study
Interim results of the POPLAR study will be presented by Dr. Alexander I. Spira, Virginia Cancer Specialists Research Institute, U.S. Oncology Research (Abstract #8010, Sunday, May 31, 4:42-4:54 P.M. CDT): Efficacy, safety and predictive biomarker results from a randomized Phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR).
The Phase II study enrolled 287 people with previously treated, advanced NSCLC. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), overall response rate (ORR) and safety. People were stratified by PD-L1 expression on tumor-infiltrating immune cells (IC), histology and prior lines of therapy. PD-L1 expression was assessed on both tumor cells (TC) and IC; and people were scored as TC 0, 1, 2 or 3 and IC 0, 1, 2 or 3 with an immunohistochemistry (IHC) test.
|
Overall Survival Results (Primary Endpoint) |
|||||||||||
|
Study Group |
TC3 or IC3 (High) |
TC2/3 or IC2/3 (Medium and High) |
TC1/2/3 or IC1/2/3 (Any Expression) |
TC0 and IC0 |
ITT (All Patients) |
||||||
|
n= |
MPDL 24 |
Doc 23 |
MPDL 50 |
Doc 55 |
MPDL 93 |
Doc 102 |
MPDL 51 |
Doc 41 |
MPDL 144 |
Doc 143 |
|
|
Median OS (months) |
NR |
11.1 |
13 |
7.4 |
NR |
9.1 |
9.7 |
9.7 |
11.4 |
9.5 |
|
|
HR* (95% CI) |
0.47 (0.20, 1.11) |
0.56 (0.33, 0.95) |
0.63 (0.42, 0.95) |
1.22 (0.69, 2.14) |
0.78 (0.59, 1.03) |
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|
CI: confidence interval; Doc: docetaxel; HR: hazard ratio; IC: tumor-infiltrating immune cell; ITT: intention to treat; MPDL: MPDL3280A; NR: not reached; OS: overall survival; TC: tumor cell. *Stratified HR for ITT and unstratified HR for subgroups. |
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|
Progression-Free Survival (Secondary Endpoint) |
||||||||||||||||
|
Study Group |
TC3 or IC3 (High) |
TC2/3 or IC2/3 (Medium and High) |
TC1/2/3 or IC1/2/3 (Any Expression) |
TC0 and IC0 |
ITT (All Patients) |
|||||||||||
|
n= |
MPDL 24 |
Doc 23 |
MPDL 50 |
Doc 55 |
MPDL 93 |
Doc 102 |
MPDL 51 |
Doc 41 |
MPDL 144 |
Doc 143 |
||||||
|
Median PFS (months) |
9.7 |
3.9 |
4.0 |
2.8 |
3.3 |
3.0 |
1.9 |
4.1 |
2.8 |
3.4 |
||||||
|
HR* (95% CI) |
0.56 (0.28, 1.11) |
0.70 (0.45, 1.08) |
0.87 (0.63, 1.20) |
1.15 (0.72, 1.82) |
0.96 (0.76, 1.20) |
|||||||||||
|
Overall Response Rate (Secondary Endpoint) |
||||||||||||||||
|
ORR (%) |
38 |
13 |
22 |
15 |
18 |
18 |
8 |
10 |
15 |
15 |
||||||
|
HR: hazard ratio; ITT: intention to treat; NR: not reached. *Stratified HR for ITT and unstratified HR for subgroups. |
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Fewer people receiving MPDL3280A experienced Grade 3 to 5 adverse events compared to docetaxel (44% vs. 56%). More respiratory events were reported for MPDL3280A. The median length of treatment with MPDL3280A was 3.7 months compared to 2.1 months for chemotherapy. Other immune-related adverse events in the MPDL3280A arm included increase of enzyme levels in the blood (aspartate and alanine aminotransferase; 4% each), inflammation in the lining of the colon (colitis; 1%), inflammation of the liver (hepatitis; 1%) and lung tissue (pneumonitis; 2%).
About MPDL3280A
MPDL3280A (also known as anti-PDL1 and RG7446) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. MPDL3280A 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, MPDL3280A may enable the activation of T cells.
About Lung Cancer
According to the American Cancer Society, it is estimated that more than 221,000 Americans will be diagnosed with lung cancer in 2015, and NSCLC accounts for 85 percent of all lung cancers. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.
About Genentech in Lung Cancer
Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have two approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.
About Genentech in 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 in our effort to bring innovative treatment options that help a person’s own immune system fight cancer. Our Personalized Cancer Immunotherapy research and development program comprises more than 20 investigational candidates, seven of which are in clinical trials. All studies include the evaluation of biomarkers to determine 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.
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