Cancer Treatment Today

In October 2015, the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application for IMLYGIC (talimogene laherparepvec), a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous and nodal lesions in patients with melanoma recurrent after initial surgery. MLYGIC is a genetically modified herpes simplex virus type 1 designed to replicate within tumors and produce an immunostimulatory protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). IMLYGIC causes cell lysis, or death, which ruptures tumors, releasing tumor-derived antigens, which along with GM-CSF, may promote an anti-tumor immune response. However, the exact mechanism of action is unknown.

KEYNOTE-037 is an ongoing Phase 1/2 study of KEYTRUDA (pembrolizumab) in combination with epacadostat (INCB024360) an investigational selective IDO1 inhibitor in patients with advanced cancers. ASTERKEY-265 is an ongoing Phase 1b study evaluating the safety, efficacy, and tolerability of KEYTRUDA in combination with IMLYGIC a herpes simplex virus-1 (HSV-1)-based oncolytic immunotherapy in patients with previously untreated, unresected advanced melanoma.

Data presented were of 16 evaluable patients and the first analysis of this study; results showed that the combination of KEYTRUDA (200 mg every two weeks) with IMLYGIC (up to 4 mL of 106 PFU/mL, then 108 PFU/mL every two weeks) resulted in an unconfirmed ORR of 56.3 percent (n=9/16) (95% CI, 19.8, 70.1), including two CRs and seven PRs. The DCR was 68.8 percent (n=11/16) (95% CI, 11, 58.7).These results await confirmation in a phase III trial.

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