Improved progression-free and overall survival (PFS/OS) in patients (pts) with emergence of JTX-2011 associated biomarker (ICOS high CD4 T cells) on the ICONIC trial

Background: ICOS is a costimulatory molecule upregulated on activated T cells. JTX-2011 is an ICOS agonist antibody intended to stimulate primed CD4 T effector cells. JTX-2011 was assessed in pts with advanced solid tumors as monotherapy (mono) and combination (combo) with nivolumab (nivo) in the Phase I/II ICONIC trial (NCT02904226). Peripheral T cell phenotyping in ICONIC demonstrated emergence of an ICOS high (hi) subset of CD4 T cells associated with tumor reductions in mono and combo pts. In ex vivo studies, soluble JTX-2011 stimulated a polyfunctional cytokine response only in ICOS hi cells. Methods: Ad hoc flow cytometry phenotyping on PBMCs from a subset of pts with evaluable samples (n=50) was initiated retrospectively in early 2018 in ongoing pts, then prospectively on newly enrolled pts. Clinical characteristics and outcomes were analyzed, including unadjusted p-values for post-hoc statistical analyses. Phenotyping was also done on samples from pts treated with PD-1/L1 inhibitor (PD-1/L1i) mono collected outside of ICONIC. Results: Emergence of ICOS hi CD4 T effector cells (all FoxP3-, subset Tbet+ Ki67+) was observed in all pts with ≥30% target lesion tumor reduction by investigator assessment on mono and combo therapy (n=7). Emergence was seen in pts with stable target lesions (n=11/23) including loss of these cells with disease progression. ICOS hi cells were not seen in ICONIC pts with target lesion increase ≥20% (n=14), or in pts treated with PD-1/L1i mono, including responders. Emergence of ICOS hi CD4 T cells correlated with improved PFS and OS (Table). Conclusion: Emergence of a distinct ICOS hi population of peripheral CD4 T cells is associated with improved PFS and OS with JTX-2011 mono and combo therapy. Two JTX-2011 development paths are planned: (1) combo with agents that induce ICOS hi CD4 T cells; (2) use of potential putative biomarkers predictive of emergence of this T cell population and JTX-2011 response. Citation Format: Timothy Anthony Yap, Justin F. Gainor, Margaret K. Callahan, Gerald S. Falchook, Russell Kent Pachynski, Patricia LoRusso, Shivaani Kummar, Geoffrey Thomas Gibney, Howard A. Burris, Scott S. Tykodi, Osama E. Rahma, Tanguy Seiwert, Kyriakos P. Papadopoulos, Ellen Hooper, Christopher J. Harvey, Amanda Hanson, Sean Lacey, Rachel McComb, Courtney Hart, Haley Laken, Ty McClure, Elizabeth Trehu. Improved progression-free and overall survival (PFS/OS) in patients (pts) with emergence of JTX-2011 associated biomarker (ICOS high CD4 T cells) on the ICONIC trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT189.