P 586 of PDF of abstracts. Results Progression free survival (PFS) rates for this treatment were 62% at 6 months and 57% at 18 months (median PFS not reached at 24 months) with a 48% BORR. DOR was not assessable as no responders have progressed and no safety signals were observed with only 2/22 grade 3 treatment-emergent adverse events. In responding patients, significant post-treatment increases were observed in both the Th1-associated gene expression of STAT4 and IL-12RB in biopsies, and frequencies of CD8+PD-1+TIGIT+ and proliferating CD8+PD-1+ peripherally. Additionally, responding patients had a significant increase of TCR clonality in the tumors compared to PBMCs with a reversed relationship in non-responding patients. Spatial analysis by mIHC revealed a significant increase of both PD-L1+ and FoxP3+ cells <15um from CD8+ T cells in non-responders. Exploratory analysis with Nanostring’s IO360 Beta Version panels highlighted underexpression of WNT2B and overexpression of MICB in the pretreatment responder biopsies. Conclusions Durable responses and favorable PFS rates in likely PD-1 non responders continues to suggest that combination IT-TAVO-EP with pembrolizumab is an effective therapeutic modality with an excellent safety profile. Associated biomarker data highlights connected immunological mechanisms, whereby intratumoral Th1-polarization, associated TCR clonality and limited suppressive cell types can drive robust anti-tumor responses (intratumoral and systemic) that positively impact this difficult to treat patient population.
