Jounce Therapeutics presents data from ICOS program at SITC annual meeting
Jounce Therapeutics announced that reverse translational and biomarker data derived from its ICONIC trial of JTX-2011 and preclinical data from the ICOS program were presented at the Society for Immunotherapy of Cancer's 33rd Annual Meeting, being held November 9-11, 2018 in Washington, D.C. Data presented from ICONIC patients demonstrate the agonistic properties of JTX-2011. These data are in addition to the subset analysis data presented at ASCO 2018 demonstrating the emergence of ICOS hi CD4 T cells in the bloodstream in all patients with greater than or equal to 30% target lesion tumor reductions, both in patients treated with JTX-2011 monotherapy and in combination with nivolumab. The ICOS hi CD4 T cells were not observed in patients with primary progressive disease. Follow-up on the initial observation of the emergence of ICOS hi CD4 T cells. Emergence of this cell population, which correlated with clinical benefit in patients treated with both JTX-2011 monotherapy and in combination with nivolumab, was presented at ASCO in June 2018. These data build upon the initial observation and provides further characterization of the emerging cell population as T effector and not T regulatory cells and includes evidence that the cells do not emerge in patients responding to PD-1 monotherapy. Additional in vitro data presented demonstrate that JTX-2011 alone induces a cytokine response from CD4 T cells, only if the T cells have pre-existing ICOS hi characteristics. CTLA-4 inhibition has been shown to induce a population of ICOS hi cells in the bloodstream, while PD-1 inhibitors do not, and these observations further support the biological rationale for the ongoing clinical development of JTX-2011 in combination with ipilimumab. The combination of radiation therapy and treatment with an ICOS agonist antibody led to increased anti-tumor response in an immunogenic mouse tumor model. In a less immunogenic tumor model, response required the combination of ICOS agonist and PD-1 antagonist with radiation, suggesting again that ICOS agonism in combination with modalities that upregulate ICOS, such as with radiation, may represent an attractive regimen for combination immunotherapy of anti-PD-1 resistant tumors.