A Study to Evaluate the Safety and Therapeutic Activity of GI-102 As a Single Agent and in Combination with Conventional Anti-cancer Drugs, Pembrolizumab or Trastuzumab Deruxtecan(T-DXd) in Patients with Advanced Solid Tumors (KEYNOTE-G08)
brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(T-DXd) over a range of advanced and/or metastatic solid tumors.
detailed description
This is a phase 1/2, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, and anti-tumor effect of GI-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(T-DXd) over a range of advanced and/or metastatic solid tumors. This study is adaptive in nature.
The study is composed of four parts:
* Part A: Dose escalation and optimization phase of GI-102 intravenous (IV) monotherapy
* Part A dose escalation phase * Part A dose optimization phase: Dose optimization cohorts in patients with 2L+, CPI-refractory metastatic melanoma * Part B: Dose escalation and expansion phase of GI-102 subcutaneous (SC) monotherapy * Part C: Indication specific cohorts of GI-102 IV in combination with conventional anti-cancer drugs or trastuzumab deruxtecan (T-DXd) * Part D: Indication specific cohorts of GI-102 IV in combination with pembrolizumab
GI-102 is a novel bi-specific Fc fusion protein containing the CD80 ectodomain as an N-terminal moiety and an interleukin (IL)-2 variant as a C-terminal moiety configurated via a human immunoglobulin G4 (IgG4) Fc. GI-102 has unique characteristics by having bispecificity to CD80 and IL2Rβγ. The CD80 portion is responsible for targeting tumor/immune cells while blocking CTLA-4 expressed on the Treg cells. The IL-2v of GI-102 is designed to abolish IL-2Rα affinity and therefore minimize the effect on Treg while it has very outstanding effect on NK and CD8 T cell proliferation and activity through IL-2Rbr affinity.
official title
An Open-label, Multicenter, Dose Escalation and Expansion Phase 1/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics, and Anti-tumor Activity of GI-102, a CD80-IgG4 Fc-IL-2v Bispecific Fusion Protein, As a Single Agent and in Combination with Conventional Anti-cancer Drugs, Pembrolizumab or Trastuzumab Deruxtecan(T-DXd) in Patients with Advanced or Metastatic Solid Tumors (KEYNOTE-G08)