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)

GI Innovation

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: doxorubicin; Drug: pembrolizumab; Drug: GI-102; Drug: bevacizumab; Drug: paclitaxel; Drug: trastuzumab deruxtecan (T-DXd); Drug: GI-102 subcutaneous (SC); Drug: eribulin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05824975

GII-102-P101

KEYNOTE-G08, MK3475-G08 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 358 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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358 participants in 7 patient groups

GI-102

Experimental group

Description:

Dose escalation: GI-102 intravenous (IV), multiple ascending doses Dose optimization: GI-102 intravenous (IV), sRP2D Dose optimization: GI-102 intravenous (IV), sRP2D-1 (or sRP2D+1)

Treatment:

Drug: GI-102

Drug: GI-102

GI-102 subcutaneous (SC)

Experimental group

Description:

Dose escalation: GI-102 subcutaneous (SC), multiple ascending doses Dose expansion: GI-102 subcutaneous (SC), sRP2D

Treatment:

Drug: GI-102 subcutaneous (SC)

GI-102 + doxorubicin

Experimental group

Treatment:

Drug: GI-102

Drug: GI-102

Drug: doxorubicin

GI-102 + paclitaxel + bevacizumab

Experimental group

Treatment:

Drug: GI-102

Drug: bevacizumab

Drug: paclitaxel

Drug: GI-102

GI-102 + eribulin

Experimental group

Treatment:

Drug: GI-102

Drug: eribulin

Drug: GI-102

GI-102 + trastuzumab deruxtecan (T-DXd)

Experimental group

Treatment:

Drug: GI-102

Drug: trastuzumab deruxtecan (T-DXd)

Drug: GI-102

GI-102 + pembrolizumab

Experimental group

Treatment:

Drug: GI-102

Drug: GI-102

Drug: pembrolizumab