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)

Sponsor: GI Innovation, Inc.

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT05824975

Patient View

This phase 1/2a open-label study assesses GI-102's safety and anti-tumor effects in advanced solid tumors. It includes dose escalation and expansion phases, with GI-102 administered via IV every 3 weeks for up to 2 years. Eligible participants are adults with adequate organ function and controlled HIV, if applicable. The study may adapt to include combination therapies based on emerging data.

Patient Parameters

Program Overview

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.

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.

Eligibility Criteria

Inclusion Criteria

  • Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening.
  • Has adequate organ and marrow function as defined in protocol.
  • Measurable disease as per RECIST v1.1.
  • ECOG performance status 0-1.
  • Adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to Grade ≤1, except alopecia and Grade 2 peripheral neuropathy.
  • HIV infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease as defined in protocol.

Key

Exclusion Criteria

  • Has known active CNS metastases and/or carcinomatous meningitis.
  • An active second malignancy.
  • Has active or a known history of Hepatitis B or known active Hepatitis C virus infection.
  • Has active tuberculosis or has a known history of active tuberculosis.
  • Active or uncontrolled infections, or severe infection within 4 weeks before study treatment administration.
  • History of chronic liver disease or evidence of hepatic cirrhosis, except patients with liver metastasis.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • Previous immunotherapies related to mode of action of GI-102.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive medications within 2 weeks prior to Cycle 1 Day 1.
  • Administration of prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
  • Radiotherapy within the last 2 weeks before start of study treatment administration, with exception of limited field palliative radiotherapy.
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1.
  • Known hypersensitivity to any of the components of the drug products and/or excipients of GI-102.

Other protocol defined inclusion exclusion criteria may apply

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