US-based clinical-stage, cancer-selective immunotherapy company Tocagen has enrolled the first patient in its Phase Ib Toca 6 study of Toca 511 (vocimagene amiretrorepvec) combined with Toca FC (extended-release 5-fluorocytosine) to treat metastatic cancers.
Toca 511 is a retroviral replicating vector (RRV) that encodes a prodrug activator enzyme, cytosine deaminase (CD).
After being specifically delivered to cancer cells, the infected cancer cells will carry the CD gene and can produce the CD enzyme known to affect cancer cells leading to apoptosis.
Toca FC is an orally administered, extended-release version of 5-fluorocytosine (5-FC), which crosses the blood-brain barrier and enters the cancer cells.
5-FC is then converted by the CD enzyme into an active anti-cancer drug, and exists at high concentrations within cancer cells already affected by Toca 511.
The trial will involve patients with colorectal cancer with liver metastases, metastatic renal cell carcinoma, locally advanced or metastatic pancreatic cancer or breast cancer, brain metastases from non-small-cell lung cancer or breast cancers and locally advanced or recurrent melanoma.
It intends to detect the expression of the Toca 511-delivered genes and resulting proteins in the tumour samples after an intravenous administration of Toca 511.
The study will also test the safety, tumour response and survival results of the company's product combination.
The first patient suffering from metastatic colorectal cancer exhibited tolerability with an intravenously administered Toca 511 and oral Toca FC. Toca 511 viral genes and CD were also observed in tumour samples.
Tocagen CEO Harry Gruber said: "With the initiation of this trial we have moved one step closer to evaluating our cancer-selective gene therapy in broad indications using intravenous Toca 511 administration.
"We are particularly encouraged by the observation of viral transduction in this first case and we look forward to enrolling additional cancer patients with high unmet needs."
In previously held Phase I studies, patients with recurrent brain cancer were administered with Toca 511 followed by Toca FC.
The Phase I studies will support Tocagen's ongoing Phase II/III study of Toca 511 and Toca FC in patients with recurrent glioblastoma and anaplastic astrocytoma.