Roche announced interim results from a global, randomised phase II study (POPLAR) in people with previously treated NSCLC. The study showed the investigational cancer immunotherapy MPDL3280A (anti-PDL1) doubled the likelihood of survival (overall survival [OS]; 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 characterised 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, MD, 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 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). Roche is discussing the interim data from POPLAR with the FDA as part of Breakthrough Therapy Designation in lung cancer. Roche currently has three Phase II and six Phase III studies of MPDL3280A ongoing in various kinds of lung cancer.
The phase II study enrolled 287 patients with previously treated, advanced NSCLC. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), overall response rate (ORR) and safety. Patients were stratified by PD-L1 expression on tumour-infiltrating immune cells (IC), histology and prior lines of therapy. PD-L1 expression was assessed on both tumour cells (TC) and IC; and patients were scored as TC 0, 1, 2, or 3 and IC 0, 1, 2, or 3 with an immunohistochemistry (IHC) test.
Fewer people receiving MPDL3280A experienced Grade 3 to 5 adverse events compared to docetaxel (44 percent vs. 56 percent). 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 (asparate 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%).
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 tumour cells and tumour-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, restoring their ability to effectively detect and attack tumour cells.