Yale researchers make progress in advanced lung cancer immunotherapy recognition and treatment
Yale researchers have potentially found a more effective treatment for non-small cell lung cancer and a better way to identify patients who are suited for these immunotherapies.
Tim Tai, Senior Photographer
A recent Yale study found that a newly developed drug could show promise in slowing the progression of non-small cell lung cancer in patients for whom previous treatments had not been effective.
Presented at the World Conference on Lung Cancer in Singapore in September, the study found that an immunotherapy medication called NC318 could increase the effectiveness of existing cancer treatments and provide an alternative treatment for patients who did not respond to prior immunotherapy.
While the study only included 18 patients — and research on NC318 is still ongoing — researchers believe that the new drug may provide an alternative treatment option for NSCLC patients who are resistant to current therapies.
“In the end, we saw 28% of our patients who had, what we felt, was benefit from this therapy,” said Scott Gettinger, Chief of Thoracic Oncology at the Yale Cancer Center and the study’s lead author. “Which is promising, considering we don’t have anything else. If what we see early on pans out, then this offers a potential salvage therapy for patients who progressed after chemotherapy and immunotherapy, which is the majority of our patients.”
Compared to chemotherapy, which indiscriminately kills all cells in the body that divide, immunotherapy boosts the immune system instead and allows the body to identify and destroy cancer cells, said Gettinger. This allows cancer patients a chance to avoid some of the adverse side effects of chemotherapy, including higher risk for infections, hair loss, and intense exhaustion.
However, research suggests that patients often develop acquired resistance to immunotherapy. In fact, an April 2023 study found that 74% of NSCLC patients who had initially responded to immunotherapy had cancer continue to grow within five years.
According to Gettinger, that’s because current immunotherapies target faulty checkpoints in the immune systems of cancer patients, called the PD1 pathway, which ordinarily target and destroy cancerous cells. But if those treatment options don’t work for patients, doctors can often be at a loss.
“What can we do for patients who don’t initially respond to PD1 inhibitor therapy or who subsequently develop resistance?” asked Gettinger.
Gettinger, alongside Roy Herbst ’84, Chief of Medical Oncology at the Yale Cancer Center, hopes to use the drug NC318 to address that challenge. In the study, 11 cancer patients, all of whom were resistant to other immunotherapy options, were given NC318. Another 18 received the treatment in combination with the current standard immunotherapy, pembrolizumab, also known as Keytruda.
Compared to existing immunotherapy options, NC318 targets another immune pathway, called Siglec-15. The study found that in the NC318-pembrolizumab combination treatment group, three patients saw a reduction in their tumor size and six patients had their tumor growth slow.
Despite the small study size, experts believe that the results are promising. Anne Chiang, a medical oncologist at the Cancer Center who was also involved in the study, saw NC318’s benefits firsthand.
“I had a patient who went on the [NC318] trial for two years, and she did so well that she finished the therapy and she has no sign of any disease,” Chiang said.
According to Chiang, the patient began the study with Stage 4 non-small cell lung cancer. Two years later, after the trial, she has no sign of disease, allowing her time to travel post-retirement.
Gettinger’s lab is also currently recruiting for another arm of the study that will test more frequent administration of the NC318 drug. According to Herbst, the drug has a short half-life, meaning that it quickly disappears from the bloodstream.
Before the drug becomes publicly available, however, NC318 will need to be approved by the US Food and Drug Administration. NextCure, the company that manufactures NC318, will now have to create a larger clinical trial with patients across the country to be granted FDA approval. Dr. Gettinger’s lab will be continuing its partnership with NextCure to conduct further research into the efficacy of NC318.
AI and immunotherapy
Herbst also conducts research that uses artificial intelligence (AI) to recognize biomarkers, an objective measure that shows whether a patient is a good candidate for a specific therapy, to create individualized treatments for lung cancer patients.
Currently, physicians manually screen scores related to the biomarker PD-L1 by examining samples of cancerous cells for the biomarker— a test used to determine if immunotherapy could work for patients, said Herbst. The biomarkers also predict whether the patients will develop resistance to immunotherapy.
In another study presented at the same World Conference on Lung Cancer in Singapore, Herbst and other researchers designed an AI system called a neural network scanning system, to screen these patients in the same way doctors would. The system scanned slides of patient samples for the presence of PD-L1.
Herbst and his team found the AI system to be more accurate than manual screenings when determining if patients were potential candidates for immunotherapy.
“We could find more patients who are actually positive with the AI, which in turn would allow us to find more patients that can be candidates for immunotherapy,” Herbst told the News.
Experts believe that AI could be a key tool for cancer therapies in the future. Chiang said that the potential for AI “is huge,” but we have only just begun learning how to use it.
The Yale School of Medicine was founded in 1810 under the supervision of the Connecticut State Medical Society.