Data from a Phase 2 clinical trial showed that combining Immune Design‘s experimental immunotherapy G100 with fractioned, low-dose radiation and Keytruda (pembrolizumab) leads to higher response rates in follicular lymphoma patients, the company announced.
The randomized trial (NCT02501473) examined if the combination was more effective than G100 plus radiation. While only 15% of patients responded to a G100-radiation regimen, the combination shrank tumors in 54% of patients. This also compares favorably to Merck‘s Keytruda, which showed an 11% response rate in a separate study.
“These are exciting new data that provide stronger translational and clinical benefit profiles of our G100 therapeutic candidate,” Carlos Paya, MD, CEO of Immune Design, said in a press release.
G100 is a synthetic small molecule designed to promote the activity and expansion of dendritic cells — a type of immune cell. Dendritic cells are key in the fight against cancer. They take up specific cancer proteins from dead cells inside the tumor and present them on the cell surface. This lets T-cells know which proteins to attack.
Combining G100 with mechanisms that kill tumor cells, such as radiation, is thought to increase the effectiveness of the treatment because it causes dendritic cells around the dead cells to activate and capture a wide range of tumor proteins.
The ongoing Phase 2 trial was designed to determine if adding Keytruda to G100 and fractioned, low-dose radiation could improve response rates in follicular and non-Hodgkin’s lymphoma. The study included 26 follicular lymphoma patients who were randomized to receive either G100 with radiation or the combination therapy.
While 54% of patients in the combination group responded to the treatment, the response rates were only 15% among those receiving G100 and radiation. Response rates were even better in patients with high TLR4 expression in the tumor, with 75% responding in the combination group.
More patients treated with the combination experienced what is known as an abscopal effect. This happens when patients see untreated tumors shrink after receiving the treatment, meaning their T-cells became tumor-specific and migrated to distant sites to eliminate other traces of tumor cells.
While 77% of patients in the combination experienced this effect, only 54% of those receiving G100 and radiation did.
The combination also increased the amount of cytotoxic T-cells, which kill cancer cells, in the tumors, compared with the other treatment group. Safety was also favorable, compared with recently approved therapies for relapsed and recurrent lymphoma.
“These new G100 data give us greater confidence in the promise of this novel therapy in follicular lymphoma, and the potential to expand into other tumors,” Paya said.
G100 received orphan drug status from both the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of follicular non-Hodgkin’s lymphoma.
