Abstract
3099 Background: HF10 is a spontaneously occurring, oncolytic, mutant Herpes Simplex Virus type 1 (HSV-1). Several deletions/insertions in its genome render it nonpathogenic. HF10 has been tested in solid tumors accessible for injection. Methods: We report correlative studies from an open label, non-randomized, multicenter, single dose escalation phase I study in patients with refractory superficial cancer. The study was a “3 + 3” design with 4-dose cohorts at escalating doses of HF10 (1 x 105 TCID50/dose with incremental dose escalations up to 1 x 107 TCID50/dose), which has been completed. Body fluids (qPCR), peripheral blood (flow cytometry) and serum (30-plex cytokine assay) were examined for viral levels, quantitative immune cell variation, and cytokines, respectively. Results: Seventeen patients were enrolled and 15 treated (9 H/N; 4 melanoma; 1 colon; 1 sarcoma). Best response was stable disease in six patients and progressive disease in nine patients. Three of the 15 patients had an adverse event possibly related to the study therapy. These AEs were grade 1 hypotension (1) and flu-like symptoms (2): typical of treatment with oncolytic viruses. qPCR analysis transiently revealed virus in the saliva of two patients (day 2 and day 22); viral clearance was achieved after 1 and 7 days respectively. Comparing the two highest and two lowest dose HF10 cohorts, CD8+PD1+ cells were decreased with increasing HF10 dose (p=0.023). Increased monocyte population (CD14+CD11c+) appeared to correlate with increased HF10 dose (p=0.063). IL-8 increased in all samples (p=0.0078 Wilcoxon Signed rank test) post injection. Conclusions: Single dose intratumoral injection was well tolerated with mild-drug related AEs and rapid viral clearance. Six patients achieved stable disease during the study period. There appears to be a generalized IL-8 related inflammatory response coincident with increased peripheral blood monocytes after HF10 administration. Decreased CD8+PD1+ cells may indicate a shift towards a non-exhausted, functional CTL phenotype. These results justify the currently accruing study of multiple administrations of HF10 at the highest administered dose. Clinical trial information: NCT01017185.
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