NCT05824975

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)

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)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 358 (estimated)
• Sponsor: GI Innovation, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Advanced Solid Tumor
• Metastatic Solid Tumor
• Soft Tissue Sarcoma (STS)
• Platinum-resistant Ovarian Cancer (PROC)
• Hepatocellular Carcinoma (HCC)
• Colorectal Cancer (CRC)
• HER2 Negative Breast Cancer
• Cutaneous Melanoma
• Renal Cell Carcinoma (RCC)

Interventions

Type	Name	Description
DRUG	GI-102 subcutaneous (SC)	0.12 mg/kg, 0.24 mg/kg or Recommended phase 2 dose of GI-102 will be administered via SC injection Q3W up to 2 years (approximately 35 years).
DRUG	GI-102	Dose level will be escalated from 0.06 mg/kg to 0.45 mg/kg and Recommended phase 2 dose (or RP2D-1, RP2D+1) of GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
DRUG	doxorubicin	Doxorubicin will be administered intravenously at a dose of 75 mg/m2 on Day 3 every 3-week (21-day) cycle for up to 6 cycles.
DRUG	paclitaxel	Paclitaxel will be administered intravenously over 1 hour at a dose of 80 mg/m2 each time weekly as a diluted solution according to the prescribing information.
DRUG	bevacizumab	Bevacizumab will be administered intravenously at a dose of 10 mg/kg every 2 weeks.
DRUG	eribulin	Eribulin will be administered intravenously at a dose of over 1.4 mg/m2 over 2 to 5 minutes on Days 3 and 10 every 3-week (21-day) cycle.
DRUG	trastuzumab deruxtecan (T-DXd)	T-DXd will be administered initially as a 5.4 mg/kg (or 6.4 mg/kg only for gastric cancer) IV over 30 - 90 minutes every 3 weeks.
DRUG	pembrolizumab	pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.
DRUG	GI-102	Recommended phase 2 dose (or RP2D-1, RP2D-2) of GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).

Timeline

• Start date: 2023-05-30
• Primary completion: 2025-11-12
• Completion: 2027-04-24
• First posted: 2023-04-24
• Last updated: 2024-11-25

Locations

11 sites across 2 countries: United States, South Korea

Regulatory

• FDA-regulated drug study