Date: 2015-05-13
Type of information: Interim results
phase: 2
Announcement: interim results
Company: Genentech, a member of Roche Group (USA - CA - Switzerland)
Product: MPDL3280A (atezolizumab)
Action
mechanism: immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. Anti-PDL1 antibody MPDL3280A is an investigational monoclonal antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. MPDL3280A is being studied in clinical trials to understand whether blocking PD-L1 will help the immune system respond to cancer. In February 2015, MPDL3280A received Breakthrough Therapy Designation from the 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.
Disease: patients with advanced or metastatic non-small cell lung cancer after platinum failure
Therapeutic area: Cancer - Oncology
Country: Belgium, Canada, France, Germany, Italy, Republic of Korea, Poland, Spain, Sweden, Thailand, Turkey, UK, USA
Trial
details: The POPLAR study is a multicenter, open-label, randomized study. It will evaluate the efficacy and safety of MPDL3280A compared with docetaxel in patients with advanced or metastatic non-small cell lung cancer after platinum failure. Patients will be randomized to receive either MPDL3280A 1200 mg intravenously every 3 weeks or docetaxel 75 mg/m2 intravenously every 3 weeks. Treatment with MPDL3280A may be continued as long as patients are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression. 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. (NCT01903993).
Latest
news: * On May 13, 2015, Genentech 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) doubled the likelihood of survival (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). 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). 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%).
