CD8+ T cell stimulation with pegylated recombinant human IL-10 in the patient with advanced solid tumors - a Phase I study

Background In preclinical studies, PEGylated IL-10 (PEG-IL-10) but not non-PEG IL-10 induces tumor rejection by the directly activating and increasing the proliferation of tumor specific CD8 T cells within the tumor. PEG-IL10 activates STAT3 and STAT1 in tumor infiltrating CD8 T cells. PEG-IL-10 induced the expression of the Th1 signature cytokine IFNg in intratumoral CD8 T cells, which was crucial for the tumor immunity. Concomitant application of PEG-IL-10 and chemotherapies did not disrupt the immune stimulation but lead to synergistic anti-tumor efficacy. Phase I study with AM0010 (PEG-hIL-10) has enrolled more than 200 patients in monotherapy and in combination arms with chemotherapies, a tyrosine kinase inhibitor and a PD-1 inhibitor. Primary objectives of this study were to establish the safety, tolerability and the MTD of AM0010 as monotherapy or in combination with chemotherapies, targeted agents or immunotherapy. Secondary objectives were to assess anti-tumor-activity, pharmacokinetics, immunogenicity and AM0010 induced immune activation.