Surface Oncology has entered a collaboration with Merck to investigate a combination of SRF617 and Keytruda (pembrolizumab) in patients with solid tumors, with a particular focus on individuals with gastric cancer and those who failed to respond to immune checkpoint inhibitors.
This combination will be investigated as part of the first-in-human Phase 1/1b clinical trial of SRF617, Surface’s investigational anti-CD39 antibody. The trial is assessing the safety and efficacy of SRF617, alone and in combination with other cancer immunotherapies, in patients with advanced solid cancers.
The open-label study is recruiting participants who have exhausted all available therapies for their condition. A total of 56 patients will be enrolled at South Texas Accelerated Research Therapeutics in San Antonio.
Its main goal is to determine the safety and tolerability of SRF617. Secondary measures include determining the proportion of patients responding to treatment, the duration of responses, and the time to disease worsening or death.
“This collaboration with Merck will add an important dimension to our clinical program for SRF617, and allow us to more rapidly assess its potential,” Robert Ross, MD, chief medical officer at Surface Oncology, said in a press release. Merck is known as MSD outside North America.
SRF617 is a human antibody that is designed to bind and block the activity of the enzyme CD39. That enzyme is involved in the production of adenosine, a molecule involved in cellular energy transfer, and in the breakdown of adenosine triphosphate (ATP), the small molecule that cells use as fuel.
By blocking CD39, SRF617 is expected to lower the levels of adenosine and to stabilize the levels of ATP found outside cells. Both are known to promote anti-cancer immune responses.
Earlier preclinical studies showed that SRF617 can stimulate the proliferation of immune T-cells — those with the ability to fight cancer — as well as inhibit tumor growth and promote the entry of immune cells into the tumor site.
These effects also are believed to increase the effectiveness of other immune checkpoint inhibitors, like Merck’s Keytruda. Such inhibitors block the activity of the PD-1 receptor cancer cells use to avoid being targeted and killed by immune cells.
“We have demonstrated in preclinical studies that the inhibition of CD39 results in substantial activation of both the innate and adaptive arms of the immune system,” Ross said. “Encouragingly, we also found that activation is heightened in combination with anti-PD-1 treatment and that this combinatory approach has the potential to overcome anti-PD-1 resistance.”
