652 NT-I7 (efineptakin alfa), a long-acting IL-7, in combination with pembrolizumab improves T cell fitness in heavily pretreated subjects with gastrointestinal tumors

BackgroundCancer patients include various populations with underlying immune dysfunction, like transplant patients or subjects with chronic infections, and subjects that are heavily pre-treated, receiving concurrent chronic steroid therapy, elderly, pregnant, or have poor performance status. Immune dysfunction curtails efficacy of immunotherapy. NT-I7 (efineptakin alfa), a long-acting IL-7, is a potent T cell amplifier that increases systemic stemness as monotherapy or in combination with checkpoint inhibitors (CPIs). Here, we explore the systemic beneficial effects of NT-I7 when combined with pembrolizumab.MethodsOpen-label Phase 2a study in subjects with relapsed/refractory CPI-naïve MSS-CRC and PDAC; NT-I7 1200 µg/kg IM every 6 weeks (Q6W), pembrolizumab 200 mg IV Q3W. Correlative studies included single cell RNA and T cell receptor (TCR) sequencing (n=27) and flow cytometry (n=53) immunophenotyping of longitudinal peripheral blood samples.ResultsAs of 04-Nov-2022, 53 subjects were enrolled and evaluable; 41 (77.4%) were treated in fourth-line or beyond. Absolute lymphocyte counts, the main pharmacodynamic biomarker for NT-I7 biological activity, significantly increased following treatment (p