Scientists at Penn Abramson Cancer Center recently presented groundbreaking results showing how combining an immune-checkpoint inhibitor – tremelimumab – with an anti-CD40 monoclonal antibody drug induces a safe and effective response in patients with metastatic melanoma. The team presented their latest findings during the section devoted to Clinical Trials of Combinations of Molecularly Targeted and Non-targeted Therapeutic Agents, in a presentation entitled “Combination of agonistic CD40 monoclonal antibody CP-870,893 and anti-CTLA-4 antibody tremelimumab in patients with metastatic melanoma” at the American Association for Cancer Research (AACR) Annual Meeting, in April 19, 2015 in Philadelphia. The study was financed by grants from Penn-Pfizer alliance grant and the National Cancer Institute (NIC), at the National Institutes of Health (NIH).
The study evaluated whether combining immunostimulatory monoclonal antibodies and immune-checkpoint inhibitors improves patients with metastatic melanoma response rates and survival. The team used an anti-CD40 monoclonal antibody drug with the immune-checkpoint inhibitor, tremelimumab. The combination therapy was administered intravenously to 24 patients with metastatic melanoma every 3 weeks (for anti-CD40) and 12 weeks (for tremelimumab).
As noted by David L. Bajor, MD, instructor of Medicine in the division of Hematology/Oncology at University of Pennsylvania, Philadelphia and study first author, “We’ve had wonderful success with immunotherapies, but we are barely scratching the surface. 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.”
After a follow-up period of 22 months, the team observed the combined therapy was not only safe but effectively reduced tumors in a subset of patients, specifically observing an overall objective response rate (ORR) of 27.3%, including a complete response in two patients (9.1%) and partial responses in four patients (18.2%). The median overall survival (OS) was registered at 26.1 months.
In light of their results, which showed tolerability, antitumor activity and immune system activation, the team strongly urges that additional studies using this combination should be pursued. Now, the team is engaging in a new study combining anti-CD40 with chemotherapy in operable pancreatic cancer patients and to test new anti-CD40 compounds.