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

Official title

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

Overview

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

Detailed description

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.

Interventions

• Drug GI-108
  Dose level will be escalated from 0.1mg/kg to 0.6 mg/kg and Recommended phase 2 dose (or RP2D) of GI-108 will be administered via IV infusion Q3W upto 2 years (approximately 35 years)

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) (Dose escalation phase) [Time frame: Study Day 1, assessed up to DLT period (3 weeks after treatment)]
• Incidence and Severity of Immune-Related Adverse Events (irAEs) (Dose escalation phase) [Time frame: From Day 1 through study completion (up to ~24 months)]
• Objective Response Rate (ORR) according to RECIST version 1.1 (Dose expansion phase) [Time frame: Study Day 1, assessed up to approximately 24 months]

Secondary outcome measures (11)

• Objective Response Rate (ORR) according to RECIST version 1.1 (Dose escalation phase) [Time frame: Study Day 1, assessed up to approximately 24 months]
• Incidence and Severity of Immune-Related Adverse Events (irAEs) (Dose expansion phase) [Time frame: Day 1 through study completion, up to ~24 months]
• Disease Control Rate (DCR) [Time frame: Study Day 1, assessed up to approximately 24 months]
• Duration of objective response (DoR) [Time frame: Study Day 1, assessed up to approximately 24 months]
• Progression-free survival (PFS) [Time frame: 6-month, 12-month, and 18-month]
• Overall survival (OS) [Time frame: 12-month and 18-month]
• Peak plasma concentration (Cmax) of GI-108 [Time frame: Study Day 1, assessed up to approximately 24 months]
• Half-life of GI-108 (T1/2) [Time frame: Study Day 1, assessed up to approximately 24 months]
• Area under the plasma concentration versus time curve (AUC) of GI-108 [Time frame: Study Day 1, assessed up to approximately 24 months]
• Clearance of GI-108 [Time frame: Study Day 1, assessed up to approximately 24 months]
• Volume of distribution (Vd) of GI-108 after administration [Time frame: Study Day 1, assessed up to approximately 24 months]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 3 centers

• Yonsei University Health System, Severance Hospital — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Identifiers

NCT: NCT07172802 · GII-108-P101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗