Massachusetts-based biotechnology company Surface Oncology (NASDAQ: SURF) has announced that it will collaborate with Merck (NYSE: MRK) on a phase 1 / phase 1b clinical trial evaluating the safety and efficacy of a solid tumor treatment approach combining Surface Oncology’s human anti-CD39 antibody candidate SRF617 with Merck’s PD-1 inhibitory antibody Keytruda (pembrolizumab).
The collaboration is part of a phase 1/1b clinical trial of SRF617 for the treatment of solid tumors, the first study of the antibody in humans, and will focus “on patients with gastric cancer and those who have developed resistance to checkpoint inhibition — both areas of high unmet need.”
Surface Oncology’s Chief Medical Officer Robert Ross, MD, stated, “Surface is committed to delivering truly breakthrough therapies that can transform treatment for people with cancer. This collaboration with Merck will add an important dimension to our clinical program for SRF617, and allow us to more rapidly assess its potential.”
“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. 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,” Dr. Ross continued.
SRF617 targets and inhibits the enzyme CD39, which is expressed on the surface of human cells and metabolizes extracellular adenosine triphosphate (eATP), an immune-stimulating danger signal, to form the immunosuppressive molecule adenosine.
According to Surface Oncology, “in gastric cancer, immune cells within the tumor often express high levels of CD39, which may impair an overall anti-cancer immune response even in the presence of an anti-PD-1 antibody. The combination of SRF617 and KEYTRUDA has the potential to overcome this barrier to immune system activation and promote anti-tumor immunity.”
In November of 2019, Surface Oncology presented a poster, “The fully human antibody SRF617 is a potent enzymatic inhibitor of CD39 with strong immunomodulatory activity,” at the annual meeting of the Society for Immunotherapy of Cancer.
The poster presented data showing that the antibody could inhibit CD-39 in vitro and in vivo, enhance the proliferation of CD4+ T cells and induce the expression of CD86 and secretion of IL-16 by monocyte-derived dendritic cells in the presence of eATP, and improve survival in the CT26 mouse model when combined with a PD-1 inhibitor, among other effects.
According to Surface Oncology, the phase 1 trial of SRF617 is the first time that the antibody has been evaluated in humans, and SRF617 “is anticipated to be one of the first CD39 antibodies to enter the clinic.”
In addition to antibody-based therapies, engineered lymphocytes are also being evaluated as potential treatment for solid tumors. Adaptimmune is exploring the anti-cancer activity of SPEAR T cells and NantKwest is evaluating the safety and efficacy of a natural killer cell-based therapy which has shown promise for the treatment of pancreatic cancer.