A team of researchers from several institutes and universities in the United States will disclose promising early results on the combination of an anti-cancer agent (MPDL3280A) and standard chemotherapy for the treatment of advanced non-small cell lung cancer (NSCLC). The data will be presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, May 29 to June 2.
Lung cancer is the leading cause of cancer deaths in the United States, with NSCLC accounting for approximately 85% of all lung cancer cases. MPDL3280A is an investigational immunotherapy against NSCLC, and is an engineered anti-PD-L1 (programmed death-ligand 1) monoclonal antibody able to target PD-L1, a protein expressed in tumor cells and tumor-infiltrating immune cells that is thought to play a major role in suppressing the body’s immune system. By inhibiting PD-L1, MPDL3280A may be able to activate immune T cells, restoring their ability to effectively recognize and attack tumor cells.
“The body needs to tightly regulate immune function,” explained in a news release ASCO abstract’s lead author Dr. Stephen V. Liu from Georgetown Lombardi Comprehensive Cancer Center. “When T-cells are activated under normal conditions, they are quickly suppressed, to prevent over-activation. This suppression is controlled by the interaction of PD1 (a receptor on the immune cells) and PD-L1, the protein that binds to the PD1 receptor. The problem is that many tumors express PD-L1 and are able to escape T-cell immunity, (…) So these drugs are designed to keep the immune signal on.”
Researchers conducted a phase 1b study in patients with untreated NSCLC who received one of three standard platinum-based chemotherapy regimens (pemetrexed/carboplatin, paclitaxel/carboplatin or nab-paclitaxel/carboplatin) together with MPDL3280A. Preliminary results from the first 37 patients revealed remarkable response rates between 60 and 75% in comparison to the 30 to 35% response rates typically seen in chemotherapy alone. Furthermore, the team reported two complete patient responses with no evidence of lung cancer on computed tomography (CT) scans.
“A complete response is not typically seen in patients with stage IV lung cancer,” noted Dr. Liu. “And the response rates seen with MPDL3280A and chemotherapy were higher than one would expect with chemotherapy alone.”
The team found that the combination therapy was overall well tolerated in the patient cohort, and that the most frequently reported adverse events were associated with chemotherapy, namely fatigue, nausea and constipation. Researchers reported that the side effects linked to MPDL3280A treatment were anemia, low levels of neutrophils (a type of white blood cell) and low platelet counts.
Anti-PD1 antibodies have already been approved for the treatment of refractory melanoma (skin cancer) and refractory squamous cell lung cancer. “MPDL3280A represents an approach at targeting not PD1, but its ligand, PD-L1, which may provide some advantages. The combination with chemotherapy in the first line setting certainly deserves further study,” concluded Dr. Liu.