A pioneering Phase 1/2 clinical trial has successfully controlled a patient’s advanced lung cancer using a combination of two immunotherapy drugs.
The ECHO-202 trial (NCT02178722) is being conducted at 20 sites in the U.S. to evaluate the safety, tolerability, and effectiveness of Keytruda (pembrolizumab) combined with epacadostat (INCB024360).
Epacadostat is an investigational drug that blocks IDO1, a protein that often plays a role in blocking the immune system’s ability to reject a foreign invader, like a cancer cell.
Keytruda has been approved by the U.S. Food and Drug Administration for advanced melanoma, non-small cell lung cancer, and selected head and neck cancers. It is an anti-PD-1 immunotherapy drug that induces shrinkage of tumors by boosting the ability of T-cells to recognize cancer cells.
Cancer cells spread throughout the body because the immune system’s key defenders, T-lymphocyte cells (or T-cells) become exhausted. One mechanism by which the tumor cells exhaust our immune systems is by expressing a protein called program death ligand 1, or PD-L1. This leads to the activation of PD-1 receptors on the surface of once-healthy T-cells, impairing them from effectively recognizing tumor cells as foreign.
The two drugs are believed to work together to invigorate the immune system, allowing cancer cells that are hidden to become more easily recognized and subsequently destroyed.
“Working together by blocking both IDO1 and PD-1, the drugs may be helping the body’s own immune system to better fight cancer and shrink the tumors in some patients,” Jeffrey Wasser, MD, oncologist and principal investigator at UConn Health’s Carole and Ray Neag Comprehensive Cancer Center, said in a press release. UConn Health is the only place in Connecticut testing the combination drug treatment.
Wasser said one patient’s tumors started shrinking just nine weeks after he began the combined immunotherapies, with each follow-up imaging scan showing better responses.
The 67-year-old man had been a heavy smoker for 50 years and was diagnosed with advanced lung cancer. He had already undergone aggressive rounds of chemotherapy and radiation, but the results were only temporary. His cancer had metastasized to stage 4 and was spreading throughout his body.
“He was very thin, barely able to walk, and was having trouble breathing. I was afraid that his lifespan would be severely reduced, as his large tumor consumed a large portion of his lung, which impaired his ability to walk and made surgery to remove it impossible,” Wasser said.
Now, a little over a year after starting his treatment in the ECHO-202 trial, the tumor has regressed significantly and doctors can barely find it.
This trial’s Phase 1 has been completed and patients are now being enrolled for the Phase 2 portion of the study. In this phase, patients with different types of tumors will be assigned standardized doses of the drugs to test their combined effectiveness. For more information about enrolling in the trial, visit NCT02178722.