City of Hope has opened a Phase 2 clinical trial designed to map how tumors change as they begin to resist immunotherapy, according to a July 21 announcement. The research will focus on advanced non-small cell lung cancer, the most common type of lung cancer, which accounts for 87% of cases.
The IMMUNO-BIOMAP trial aims to enroll 535 patients newly diagnosed with non-small cell lung cancer over six years. The project is funded by an award of up to $23.7 million from the Advanced Research Projects Agency for Health (ARPA-H) and led by Ravi Salgia, Jyoti Malhotra, and Aritro Nath at City of Hope. Researchers plan to use predictive models to tailor treatments based on the evolving biology of patients' tumors.
Doctors treating advanced non-small cell lung cancer often rely on immune checkpoint inhibitors that target PD-L1 proteins on cancer cells. However, fewer than 40% of patients respond positively and many develop resistance. The Beckman Research Institute team at City of Hope will investigate biomarkers—biological clues that may help match cancers with effective treatments—and explore circulating tumor DNA for new strategies aimed at prolonging positive responses.
In the second phase, researchers intend to introduce new therapies guided by these biomarkers in real time. They will focus particularly on how second-line immunotherapy drugs address resistance in tumors with specific genetic mutations known for driving growth and spread. "Our ultimate goal is to identify groups of patients who respond well to personalized treatments and biomarker-guided therapies, allowing them to live longer without relapse," Dr. Salgia said. "With the support of ARPA-H, these findings could mark a new era in the fight against lung cancer." City of Hope is currently the only institution in the nation receiving ARPA-H funding for lung cancer research under this initiative.
The ADAPT program from ARPA-H is a $142 million initiative aiming to integrate advanced technologies with expertise in tumor biology for personalized care that adapts as disease progresses. The study will also assess whether combining immunotherapy with other treatments improves outcomes compared with chemotherapy alone.
"Late-stage non-small cell lung cancer is unique in that a patient's response to initial therapy often influences the success of later treatment," said principal investigator Aritro Nath. Principal investigator Jyoti Malhotra added, "Measuring tumor DNA levels in the blood over time will help us pinpoint which patients face a greater risk for drug resistance and relapse after immunotherapy... Understanding how checkpoint drugs interact with tumor cells will allow us to tailor treatment plans based on each patient's unique cancer DNA signature."
