Association Of Response To Programmed Death Receptor 1 (Pd-1) Blockade With Pembrolizumab (Mk-3475) With An Interferon-Inflammatory Immune Gene Signature.

3001 Background: Immunotherapy with anti–PD-1 monoclonal antibodies such as pembrolizumab shows robust, durable antitumor activity in patients with advanced melanoma. Examining gene expression related to the immune response within the tumor may provide new insights into the molecular features associated with clinical response to these agents. We evaluated immune-related gene expression patterns in patients with melanoma enrolled in the phase Ib KEYNOTE-001 study. Methods: Baseline tumor biopsy samples from 19 patients with melanoma enrolled in KEYNOTE-001 were used as a discovery set. Results were validated using samples from 62 additional patients from KEYNOTE-001, of whom 51 were evaluable for response per RECIST v1.1 by central review. RNA was extracted from formalin-fixed paraffin-embedded tissue sections and analyzed using the NanoString nCounter. Two signatures, the “Interferon-gamma [IFNγ] 10-gene” and the “Expanded-immune 28-gene,” were pre-specified prior to linking NanoString data to clinical ou...