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Lung cancer is the leading cause of cancer death in the United States for both men and women. About 80% to 85% of all lung cancers are non-small cell lung cancer (NSCLC), a term that classifies a group of slow-growing, similarly characterized diseases.

Immune checkpoint inhibitor therapy, a type of immunotherapy, is often used to treat advanced non-small cell lung cancer.

In a phase 1B study led by Jhanelle Gray, MD, chair of the Department of Thoracic Oncology at Moffitt Cancer Center, researchers evaluated the use of a messenger RNA-based cancer vaccine to improve upon immune checkpoint blockade therapy in patients with advanced-stage, previously treated NSCLC.

“There are a few immune checkpoints we think are important in the therapeutic landscape for non-small cell lung cancer,” Gray said. “Some are further advanced than others, those being anti-PD-1/anti-PD-L1, as well as anti-CTLA-4. But there’s some debate in the field over which patients can receive just one agent, and which need combination therapy.”

What we wanted to determine was does this impact outcomes for our patients, but the bigger question was is this safe?
Jhanelle Gray, MD

In this study conducted at multiple sites across the U.S., including in partnership with NYU Langone’s Perlmutter Cancer Center, clinical researchers evaluated what would happen when an mRNA-based cancer vaccine was added to durvalumab (an anti-PD-L1) and what would happen when it was added to a combination of durvalumab plus tremelimumab (an anti-CTLA-4).

“What we wanted to determine was does this impact outcomes for our patients, but the bigger question was is this safe?” Gray said.

headshot of Dung-Tsa Chen, PhD

Dung-Tsa Chen, PhD

Dung-Tsa Chen, PhD, a biostatistician at Moffitt and co-author on the study, presented results from the trial at the 2024 American Association for Cancer Research annual meeting.

Gray says data collected from the numerous patients accrued throughout the study demonstrated that combining an mRNA vaccine therapy with anti-PD-L1 therapy plus or minus anti-CTLA-4 therapy is indeed safe. The data also favors that when using an mRNA-based cancer vaccine approach, it may be better to administer only in combination with durvalumab, the anti-PD-L1 therapy.  

The study began pre-COVID prior to the rapid acceleration of the development of mainstream mRNA vaccines like the COVID vaccine, Gray notes.

“Learning from different disciplines in medicine is so important and that’s a lesson we gleaned through COVID,” Gray said. “We deployed this study before that, and we know a lot more now. I hope that we can continue to expand and build upon these findings, not only in advanced lung cancer but also in earlier stages and even across different tumor types.”