Dr. Milhem on the Utility of RP1 in Solid Tumors

Mohammed Milhem, MBBS, the Holden Chair of Experimental Therapeutics, associate director of clinical research and director of the Melanoma Program, Holden Comprehensive Cancer Center, director of the Division of Hematology, Oncology, and Blood & Marrow Transplantation, and a clinical professor at the University of Iowa Hospitals & Clinics, discusses the utility of vusolimogeneoderparepvec (RP1) in solid tumors.

RP1 leverages an engineered herpes simplex type 1 virus. Currently, RP1 monotherapy and RP1 plus nivolumab (Opdivo) are being evaluated in an open label, dose escalation and expansion phase 1/2 trial (NCT03767348).

RP1 is administered through an intertumoral injection, delivering the modified herpes directly into the tumor, Milhem says. However, due to a loss in virulence, the virus attacks the tumor cells, rather than healthy host cells, Milhem adds. Moreover, the virus replicates inside the tumor and takes over the DNA, which is then replaced by the viral DNA, leading to the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), the tumor’s killer, Milhem explains.

Additionally, GM-CSF is made in large amounts, luring white blood cells to the tumor, Milhem notes. In the presence of an anti–PD-1, where program cell death is blocked on the T cells, it is possible to have a better and more robust presentation of the tumor to the immune system, where T cells are working harder because of the PD-1, Milhem concludes.