A Phase I study of KH901, a conditionally replicating granulocyte-macrophage colony-stimulating factor Armed oncolytic adenovirus for the treatment of head and neck cancers

Background: KH901 is a conditionally replicating oncolytic adenovirus, which reported selectively replicates in and lyses telomerase-positive tumor cells and expresses granulocyte macro-phase colony-stimulating factor (GM-CSF). To determine the safety, feasibility and biological activity of KH901, a conditionally replicating oncolytic adenovirus, in patients with recurrent head and neck cancer (HNC). Results: Treatment was well tolerated, with the main toxicity being grade 1/2 flu-like symptoms. Dose-limiting toxicity was not reached in either single dose groups or multiple dose groups. KH901 was detected in urine, but little was found in feces. Interestingly, a second peak of detectable KH901 genome found in the circulation in majority of patients tested between 2 and 4 days after treatment. High level of GM-CSF in circulation was detected in all single dose patients 12 h and became undetectable 15 days following injection. All 23 patients treated showed an increase in neutralizing antibody to adenovirus. Materials and methods: Twenty-three patients with recurrent HNC was administered by intratumoral injection in two parts of trial. In the single dose escalating portion, four cohort of 13 patients received a single injection of KH901 at a dose of 3 x 10(11) virus particle (vp), 1 x 10(12) vp, 3 x 10(12) vp and 1 x 10(13) vp, respectively, while in the multiple dose portion each cohort of six patients received twice weekly a total of six injections at a dose of either 1 x 10(12) vp or 3 x 10(12) vp. Toxicity was assessed using NCIC criteria. Tumor response was assessed by clinical and radiological measurement. Blood samples were taken to detect adenovirus DNA, GM-CSF expression and neutralizing antibody to adenovirus. Conclusions: These preliminary results showed that intratumoral administration of KH901 was feasible, well tolerated and associated with biological activity, further investigation of KH901, particularly in combination with systemic chemotherapy, was warranted.