ECC 2013: Novel Anti-PD-L1 Antibody Achieves Durable Responses in Phase I Study of Patients With Metastatic NSCLC, Smokers Included
For the first time, an immunotherapy shows promise in smokers with non–small cell lung cancer (NSCLC). The engineered monoclonal antibody MPDL3280A achieved encouraging and durable responses in a phase I study in metastatic NSCLC in smokers and nonsmokers, and with squamous and adenocarcinoma histology. Responses were more robust in smokers than nonsmokers, which is not what usually happens in drug trials of NSCLC, explained lead author Jean-Charles Soria, MD, of Institut Gustave Roussy, Paris, at the European Cancer Congress 2013 in Amsterdam (Abstract 3408).
Although this is only a phase I trial, experts were enthusiastic about this new approach. “These results are so exciting that perhaps we should leap to a phase III trial,” said Paul Baas, MD, of the Netherlands Cancer Institute in Amsterdam, formal discussant of this abstract.
MPDL3280A inhibits the PD-L1/PD-1 pathway, preventing cells from escaping detection by the immune system, Dr. Soria told listeners. He was particularly enthusiastic that the antibody achieved a better response in smokers than in nonsmokers.
“This is great news for lung cancer patients—the majority of whom are current or former smokers. The data are preliminary, but the trends are extremely promising,” Dr. Soria said.
Study Details
The cohort of NSCLC patients in this ongoing phase I study included 85 patients evaluable for safety and 53 for efficacy. This was a heavily pretreated group, and 81% were current or former smokers. The NSCLC cohort is the largest group of patients treated with anti-PD-L1 blockade to date.
The antibody was given as an intravenous infusion every 3 weeks for a median duration of 48 weeks.
Overall objective response rate was 21% in all 175 patients enrolled in the phase I trial, with objective response rate in the NSCLC cohort being 23%. Responses were stable over 24 weeks in responders. According to Dr. Soria, with the exception of one patient, all responders were still in response as of May 2013.
The 24-week progression-free survival rate was 44% in patients with squamous cell NSCLC and 46% in those with nonsquamous histologies.
Smoking Status, PD-L1 Expression Are Predictive of Response
Two factors were predictive of response: level of PD-L1 expression on immunohistochemistry and smoking status. Objective response rate was increased as PD-L1 expression increased. Conversely, progressive disease decreased with higher PD-L1 expression. Using an immunohistochemistry scoring system for PD-L1 (range, 0-3), overall response rate was 46% in patients with a score of 2/3 vs 83% in those with scores of 3. Objective response rate was 26% (n = 43) for smokers and former smokers vs 10% in never-smokers (n = 10).
MPDL3280A appeared to be well tolerated in this trial. The majority of adverse events were mild (grade 1 and 2). Adverse events of any grade were reported in 56 (66%) patients. Grade 3 and 4 adverse events were reported in 9 (11%) patients. No dose-limiting toxicities were identified, and there were no reports of grades 3 to 5 pneumonitis or diarrhea.
Genentech has an extensive development plan for MPDL3280A, and the antibody is moving forward in phase II and III trials. If the preliminary results hold true, for the first time NSCLC will have an immunotherapy that works independent of smoking status.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
