Although immunotherapies have shown promise in treating non-small cell lung cancer (NSCLC), many patients still do not respond well, and those who do may eventually develop resistance. In a new study, Yale Cancer Center researchers at Yale School of Medicine tested a new immunotherapy, NC318, in combination with the targeted immunotherapy, pembrolizumab (KEYTRUDA). The study's findings suggest that NC318, both alone and in combination with pembrolizumab, improved response rates and clinical outcomes for some patients with NSCLC.
The researchers present their findings at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Singapore on Sept. 12. The research team partnered with the developer of NC318, NextCure, on this phase II trial.
“Our goal is to offer patients with non-small cell lung cancer more effective options, especially when other treatments may fall short,” said the study’s senior author Roy S. Herbst, MD, PhD, deputy director of Yale Cancer Center and assistant dean of translational research at Yale School of Medicine. “The fact that NC318, in combination with pembrolizumab, is well-tolerated in patients who had previously been treated with immune checkpoint inhibitors is encouraging. It provides another treatment for patients in need of therapeutic options for advanced lung cancer."
In the trial, researchers administered NC318 either alone or in combination with pembrolizumab to patients with advanced NSCLC that had progressed after receiving checkpoint inhibitor therapy. Among the 11 patients who received NC318 alone, one patient had a partial response, two had stable disease (tumor size did not grow or shrink), and eight patients had progressive disease (at least a 20% growth in tumor size).
Among the 18 patients who received the NC318-pembrolizumab combination treatment, three patients had a partial response (one after initial pseudo-progression), six patients had stable disease, and nine patients had progressive disease. Two of the patients with stable disease had ongoing stability at 21.6 months and 7.6 months, respectively.
Some patients experienced treatment-related adverse events, but researchers say the overall tolerability was good, similar to standard immunotherapy.
“Although the data is promising, these are preliminary findings and further research is ongoing with a focus on optimizing treatment dose and schedule, and evaluating predictive biomarkers,” said the study’s first author Scott Gettinger, MD, chief of thoracic medical oncology at Yale Cancer Center and Smilow Cancer Hospital.
Gettinger and Herbst were joined by Yale co-authors Sarah Goldberg, Anne Chiang, Frederick Wilson, So Yeon Kim, Elin Rowan, Heather Gerrish, Emily Duffield, Marianne Davies, Vanna Dest, Roliya Jackson, Jennifer Pope, Wei Cheng, David Rimm, and Lei Chen.