“While immunotherapy has transformed the treatment landscape for non-small cell lung cancer, most patients do not achieve durable responses to checkpoint inhibitors,” notes Dr. Jain. “These results from our early-phase clinical trial of the investigational drug JNJ-86974680 suggest that targeting the adenosine pathway — a major driver of immunosuppression in the tumor microenvironment — may offer a promising new strategy for improving outcomes with immunotherapy in this disease.”
The multicenter phase 1 study (NCT06116786) evaluates JNJ-86974680, a small-molecule A2a receptor antagonist developed by Johnson & Johnson. The drug is designed to block adenosine-mediated immunosuppression by inhibiting A2a receptors on immune cells, potentially restoring T-cell activity against tumors.
In part 1 of the study, which assessed safety and dose-finding, no dose-limiting toxicities were observed when JNJ-86974680 was administered alone or in combination with cetrelimab, an investigational PD-1 inhibitor. Among 41 patients with advanced NSCLC who had progressed on prior anti-PD-1 therapy, stable disease was the best overall response, with one patient remaining on treatment for more than eight months.
“Importantly,” notes Dr. Jain, “JNJ-86974680 demonstrated near-complete blockade of A2a receptors on circulating immune cells — a pharmacodynamic effect that may further improve as the optimal tumor-penetrating dose is determined.”
Part 2 of the trial also includes radiation to metastatic lesions, combining JNJ-86974680, cetrelimab and radiation therapy to explore whether adenosine blockade can further sensitize tumors to immunotherapy — including in patients who have not previously received immunotherapy.
The team found that JNJ-86974680 almost completely blocked A2a receptors in immune cells circulating in the blood. They hope that effect will increase as they determine the optimal dose and the drug concentrates inside the tumor.
In addition to Roswell Park, the study team includes investigators from Johnson & Johnson and other leading institutions in the United States, South Korea, Spain and Germany. Brian Henick, MD, of Columbia University’s Herbert Irving Comprehensive Cancer Center served as senior author of the study.
The ongoing study, which is sponsored by Johnson & Johnson, is open for accrual at Roswell Park and other sites. For information about this study or other clinical trials at Roswell Park, call 1-800-ROSWELL (1-800-767-9355) or email [email protected].
From the world’s first chemotherapy research to the PSA prostate cancer biomarker, Roswell Park Comprehensive Cancer Center generates innovations that shape how cancer is detected, treated and prevented worldwide. Driven to eliminate cancer’s grip on humanity, the Roswell Park team of 4,000 makes compassionate, patient-centered cancer care and services accessible across New York State and beyond. Founded in 1898, Roswell Park was among the first three cancer centers nationwide to become a National Cancer Institute-designated comprehensive cancer center and is the only one to hold this designation in Upstate New York. To learn more about Roswell Park Comprehensive Cancer Center and the Roswell Park Care Network, visit http://www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email [email protected].
Media Contact
Annie Deck-Miller, Roswell Park Comprehensive Cancer Center, 716-845-8593, [email protected], roswellpark.org
SOURCE Roswell Park Comprehensive Cancer Center
