A Study of GI-108, an Anti-CD73-IgG4 Fc-IL-2v Bispecific Fusion Protein, as Monotherapy in Patients With Advanced or Metastatic Solid Tumors

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-108, an Anti-CD73-IgG4 Fc-IL-2v Bispecific Fusion Protein, as a Single Agent in Patients With Advanced or Metastatic Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-108, as a single agent, in patients with advanced or metastatic solid tumors

This is an open-label, multicenter, dose escalation and expansion, phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of GI-108 as a single agent in advanced or metastatic solid tumors. A control arm is not included.

The study is composed of two phases:

• Dose escalation phase
• Dose expansion phase The dose escalation phase will enroll up to 36 patients with advanced or metastatic solid tumors. At least 3 dose-limiting toxicity (DLT) evaluable patients will be enrolled in each cohort during the dose escalation to establish a maximum tolerated dose (MTD) or tentative recommended phase 2 dose (RP2D). Enrollment in each cohort may be extended to enroll additional 4~7 patients (aiming to recruit upto 10 patients including DLT evaluable patients per cohort), potentially enriched in certain tumor types and/or characteristics to confirm safety, PK and/or pharmacodynamics (PD) of GI-108. The Safety Monitoring Committee (SMC) will determine extension of each cohort based on the review of all available clinical data including efficacy, safety, PK and/or PD. Of the 4 planned cohorts in the dose escalation phase, up to 3 cohorts may be extended to include additional patients based on safety, efficacy PK and/or PD data. The evidence of enrollment extension should be documented for each cohort during dose escalation phase.

Key Inclusion Criteria:

• Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatoryguidelines) 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 steroidtherapy or any other form of immunosuppressive medications within 2 weeksprior to Cycle 1 Day 1.