A phase 1B trial of vocimagene amiretrorepvec in patients with advanced solid tumors: Safety, tumor homing, and immune modulatory effects
Abstract
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.
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 21 participants or records.
Read the paper
Related studies
- Understanding the factors influencing fall armyworm (Spodoptera frugiperda J.E. Smith) damage in African smallholder maize fields and quantifying its impact on yield. A case study in Eastern Zimbabwe
- Alarming situation of emerging H5 and H7 avian influenza and effective control strategies
- Livestock and food security: vulnerability to population growth and climate change
- Atmosphere–ocean oxygen and productivity dynamics during early animal radiations
- Characterization of the global distribution and diversified plasmid reservoirs of the colistin resistance gene mcr-9
- The global seroprevalence of Toxoplasma gondii in pigs: A systematic review and meta-analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.