Abstract CT189: 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). ICONIC Pt characteristicsICOS hi (N=18)ICOS low (N=32)≥3 prior therapies, n (%)13 (72.2)18 (56.3)Prior immunotherapy, n (%)6 (33.3)15 (46.9)Tumor type, n (%)Gastric n=9 (50), NSCLC n=3 (16.7), TNBC n=2 (11.1), Other n=4 (22.2)Gastric n=8 (25), NSCLC n=6 (18.8), TNBC n=4 (12.5), Other n=14 (43.8),Mono vs Combo, n (%)Mono n=2 (11.1), Combo n=16 (88.9)Mono n=11 (34.4), Combo n=21 (65.6)G3-4 treatment-related adverse events, n (%)1 (5.6)2 (6.3)Time on JTX-2011, median mths (range), p=0.00065.6 (1.45-18.4)1.41 (0.03-6.28)PFS, investigator and central imaging review, median mths, (investigator, p