Immune Checkpoint Inhibitors in Melanoma: New Directions


The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…


New Combo of Immunotherapy Drugs Is Safe, Shrinks Tumors in Metastatic Melanoma Patients

“Once again, researchers at Penn’s Abramson Cancer Center have extended the reach of the immune system in the fight against metastatic melanoma, this time by combining the checkpoint inhibitor tremelimumab with an anti-CD40 monoclonal antibody drug. The first-of-its-kind study found the dual treatments to be safe and elicit a clinical response in patients, according to new results from a phase I trial to be presented at the AACR Annual Meeting 2015 on Sunday, April 19.

“Researchers include first author David L. Bajor, MD, instructor of Medicine in the division of Hematology/Oncology, and senior author Robert H. Vonderheide, MD, DPhil the Hanna Wise Professor in Cancer Research.

” ‘We’ve had wonderful success with immunotherapies, but we are barely scratching the surface,’ Bajor said. ‘Checkpoint inhibitors are just the beginning. When they are thoughtfully combined with immune-stimulating compounds like CD40 or drugs targeting other facets of the immune system we hope to be able to increase the response rate to previously approved therapies.’

“Known as a checkpoint inhibitor, tremelimumab is an investigational monoclonal antibody that ‘cuts the brakes’ of the immune system by targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), a protein that can switch off a patient’s immune response. Anti-CD40 drugs (in this trial, CP- 870,893) antagonize the CD40 receptor, and effectively ‘push the gas’ on the immune system to make it work harder.”