9 hours Ago By Roswell Park Comprehensive Cancer Center
Highlights Investigational drug shows activity in anti-PD1-resistant lung cancer Targeting adenosine may enhance effectiveness of immunotherapy Favorable safety/tolerability profile observed Newswise — BUFFALO, N.Y. and CHICAGO — Patients with advanced non-small cell lung cancer (NSCLC) are often treated with immunotherapy drugs known as checkpoint inhibitors, which are designed to strengthen the immune system’s ability to kill cancer cells — but these drugs do not produce a lasting response in most patients with this cancer type.
Initial results of a phase 1 clinical trial of the investigational drug JNJ-86974680 reveal that it has the potential to overcome that limitation. Prantesh Jain, MD, FACP , Assistant Professor of Oncology, Department of Medicine at Roswell Park Comprehensive Cancer Center, will share initial results of the study Tuesday during the 2025 annual meeting of the American Association for Cancer Research (AACR) in Chicago, Illinois. Dr.
Jain is the presenting and first author of abstract CT137, “ Initial results from a phase 1 study of an A2a receptor antagonist, administered as monotherapy and in combination with anti-PD1 therapy in patients with advanced non-small cell lung cancer ,” to be presented Tuesday, April 29, from 9 a.m.-noon CDT, in Section 48, board 3 as part of the poster session First-in-Human Phase 1 Clinical Trials 2.
“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] ..
