IVAC MUTANOME: A first-in-human phase I clinical trial targeting individual mutant neoantigens for the treatment of melanoma

Abstract

Background: IL-10 is anti-inflammatory and stimulates the cytotoxicity and proliferation of CD8þ T cells at higher concentrations. IL-10 receptors and PD1 are expressed on activated and exhausted CD8 T cells, providing a rationale for combining AM0010 and an anti-PD1 antibody. 4 of 16 heavily pre-treated pts with poor-or intermediate-risk mRCC, achieved a PR with AM0010 alone. Methods: 38 pts with metastatic RCC were enrolled from 2/20/2015 to 11/18/16 on AM0010 (10 or 20 ug/kg daily SC) and nivolumab (n ¼ 29; 3mg/kg, q2wk IV) or pem-brolizumab (n ¼ 9; 2mg/kg, q3wk IV). Three had favorable and 30 had intermediate or poor-risk by IMDC (5 data not available). Pts had a median of 1 prior therapy (range: 1-3), and at least one VEGFR-TKI. One patient with prior AM0010 was included the safety population only. Tumor responses were assessed by irRC. Serum cytokines, blood derived T cells, clonal identity of peripheral T cells, and tumor DNA sequence and mRNA profiling were assayed. Results: AMO010 plus nivolumab (nivo) or pembrolizumab (pembro) was well tolerated. TrAEs were reversible and transient.