Overview
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-102 as a single agent over a range of advanced and/or metastatic solid tumors.
Description
This is a phase 1/2a, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, and anti-tumor effect of GI-102 as a single agent over a range of advanced and/or metastatic solid tumors. This study is adaptive in nature. While GI-102 is being investigated as a single agent in this trial, GI-102 has the potential of being combined with other agents. Based on the data from ongoing nonclinical studies and the dose escalation phase, additional combination therapies [GI-102 + drug(s) X] may be proposed and added to this study protocol via an amendment.
This study will comprise two phases.
- GI-102 monotherapy dose escalation phase
- GI-102 monotherapy dose expansion phase
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
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