A phase 1B trial of vocimagene amiretrorepvec in patients with advanced solid tumors: Safety, tumor homing, and immune modulatory effects.

Vocimagene amiretrorepvec (Toca 511) is a replicating retroviral vector (RRV) encoding cytosine deaminase that converts 5-fluorocytosine (5-FC) into 5-fluorouracil in the tumor microenvironment. This study investigated the safety and immunomodulatory effects of systemically administered Toca 511 and Toca FC in advanced cancer patients. Eligible subjects received three daily intravenous (i.v.) injections of Toca 511, followed by intratumoral (i.t.) injection of Toca 511, and a 7-day course of oral Toca FC given every 4-6 weeks. Among 21 enrolled patients, the most common treatment-related adverse events were diarrhea, nausea, vomiting, and fever. Correlative studies confirmed tumor homing after intravenous virus administration. Addition of Toca FC reduced tumor myeloid cells, Tregs, and exhausted T cells, and increased CD8 T cells. Systemically, a shift in T cells from naive to effector phenotypes, expansion of CD4 memory T cells, and increases in B cells were observed. Treatment was associated with a disease control rate of 61% and median overall survival of 9.6 months. The above results confirm feasibility of systemic administration of Toca 511 in combination with oral Toca FC, successful tumor targeting, and tumor and systemic immunomodulation. Further investigation of Toca 511/Toca FC in combination with checkpoint inhibitors and/or targeted agents is warranted.