470 A phase 1/2, open-label, dose escalation and expansion study of GI-101 as a single agent and in combination with a pembrolizumab, lenvatinib or local RT in advanced solid tumors (KEYNOTE-B59)

Background GI-101 is a novel bispecific fusion protein containing CD80 and interleukin-2 (IL-2) variant, designed to exhibit high affinity cytotoxic T-lymphocyte-associated 4 (CTLA4) preferential binding IL-2R? subunit. In various animal models, exerted strong anti-tumor efficacy, accompanied by robust stimulation of CD8+ T NK cell proliferation without significant increase in regulatory cells. also elicited synergistic efficacy when used combination with pembrolizumab (anti-PD1 agents), lenvatinib (tyrosine kinase inhibitor) radiation vivo. 1 Given the complementary mechanisms action via blocking CTLA4 IL-2 activity enhance activation effector cells, it was hypothesized that as single agent or other immunotherapies, VEGF inhibitors RT may exert cancers unmet needs. Methods KEYNOTE-B59 ( NCT04977453 ) an ongoing phase 1/2 study composed parts. This planned enroll approximately 374 patients across indications. Patients assigned Part A B receive either monotherapy (Part A) + 200 mg B) IV infusion on every 3 weeks (q3w). C, will q3w (oral, once daily). D, be given local tumor irradiation. Each part initiated dose-escalation/optimization phases which advanced solid tumors, except D enrolls melanoma sarcoma only. utilizes conventional 3+3 design determine maximum tolerated dose recommended 2 (RP2D) combination. Once RP2D determined, enrolled dose-expansion each includes specific types, such failed standard care, treatment-naïve unselected CPI-treated tumors. tumors recovered from prior therapy enrolled. assess safety, tolerability, dose-limiting toxicities, MTD, RP2D, preliminary activity, pharmacokinetics/pharmacodynamics Results currently enrolling metastatic Acknowledgements The authors would like thank all who are participating this study. sponsored GI Innovation, Inc. Trial Registration Reference Pyo KH, Synn CB, Koh YJ, et al. Comprehensive preclinical GI-101, CD80-IgG4-IL2 variant protein, therapeuticantibody candidate immuno-oncology target. Cancer Res 2021; 81 (13_Suppl). Ethics Approval approved Severance hospital institutions’ Review Board (IRB); approval number 4-2021-0185, Asan Medical center‘s IRB; 2021-0669.