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)
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-102, a CD80-IgG4 Fc-IL-2v Bispecific Fusion Protein, As a Single Agent and in Combination with Conventional Anti-cancer Drugs, Pembrolizumab or Trastuzumab Deruxtecan(T-DXd) in Patients with Advanced or Metastatic Solid Tumors (KEYNOTE-G08)
2 other identifiers
interventional
358
2 countries
11
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2023
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 28, 2023
CompletedFirst Posted
Study publicly available on registry
April 24, 2023
CompletedStudy Start
First participant enrolled
May 30, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 12, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
April 24, 2027
ExpectedNovember 25, 2024
November 1, 2024
2.5 years
March 28, 2023
November 21, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Incidence and nature of Dose-Limiting Toxicity (DLTs) (dose escalation phase of Part A and B)
A DLT is defined as a clinically significant AE (classified according to the NCI CTCAE version 5) or significant laboratory abnormality that occur during the DLT assessment periods, during dose escalation and dose expansion, and is considered by the Investigator to be related to GI-102.
Study Day 1, assessed up to DLT period (3 weeks after treatment)
Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) (dose escalation phase of Part A and B)
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Study Day 1, assessed up to approximately 24 months
Objective Response Rate (ORR) (dose optimization phase of Part A, dose expansion phase of Part B, Part C and D)
ORR is defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).
Study Day 1, assessed up to approximately 24 months
Secondary Outcomes (12)
Objective Response Rate (ORR) (dose escalation phase of Part A and B)
Study Day 1, assessed up to approximately 24 months
Incidence and nature of Dose-Limiting Toxicity (DLTs) (dose optimization phase of Part A, dose expansion phase of Part B, Part C and D)
Study Day 1, assessed up to DLT period (3 weeks after treatment)
Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) (dose optimization phase of Part A, dose expansion phase of Part B, Part C and D)
Study Day 1, assessed up to approximately 24 months
Disease Control Rate (DCR)
Study Day 1, assessed up to approximately 24 months
Duration of objective response (DoR)
Study Day 1, assessed up to approximately 24 months
- +7 more secondary outcomes
Other Outcomes (4)
Incidence of anti-GI-102 antibody (ADA) and neutralizing antibody (Nab)
Study Day 1, assessed up to approximately 24 months
Immunophenotyping of peripheral blood CD4+ T cells
Study Day 1, assessed up to approximately 24 months
Immunophenotyping of peripheral blood CD8+ T cells
Study Day 1, assessed up to approximately 24 months
- +1 more other outcomes
Study Arms (7)
GI-102
EXPERIMENTALDose 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)
GI-102 subcutaneous (SC)
EXPERIMENTALDose escalation: GI-102 subcutaneous (SC), multiple ascending doses Dose expansion: GI-102 subcutaneous (SC), sRP2D
GI-102 + doxorubicin
EXPERIMENTALGI-102 + paclitaxel + bevacizumab
EXPERIMENTALGI-102 + eribulin
EXPERIMENTALGI-102 + trastuzumab deruxtecan (T-DXd)
EXPERIMENTALGI-102 + pembrolizumab
EXPERIMENTALInterventions
0.12 mg/kg, 0.24 mg/kg or Recommended phase 2 dose of GI-102 will be administered via SC injection Q3W up to 2 years (approximately 35 years).
Dose level will be escalated from 0.06 mg/kg to 0.45 mg/kg and Recommended phase 2 dose (or RP2D-1, RP2D+1) of GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
Doxorubicin will be administered intravenously at a dose of 75 mg/m2 on Day 3 every 3-week (21-day) cycle for up to 6 cycles.
Paclitaxel will be administered intravenously over 1 hour at a dose of 80 mg/m2 each time weekly as a diluted solution according to the prescribing information.
Bevacizumab will be administered intravenously at a dose of 10 mg/kg every 2 weeks.
Eribulin will be administered intravenously at a dose of over 1.4 mg/m2 over 2 to 5 minutes on Days 3 and 10 every 3-week (21-day) cycle.
T-DXd will be administered initially as a 5.4 mg/kg (or 6.4 mg/kg only for gastric cancer) IV over 30 - 90 minutes every 3 weeks.
pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GI Innovation, Inc.lead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (11)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224, United States
Mayo Clinic in Minnesota
Rochester, Minnesota, 55905, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Seoul National University Hospital
Seoul, Seoul, 03080, South Korea
St. Vincent's Hospital
Suwon, suwon, 12647, South Korea
Yonsei University Health System, Severance Hospital
Seoul, 03722, South Korea
Yonsei University Health System, Severance Hospital
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Nari Yun, PhD
GI Innovation, Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 28, 2023
First Posted
April 24, 2023
Study Start
May 30, 2023
Primary Completion
November 12, 2025
Study Completion (Estimated)
April 24, 2027
Last Updated
November 25, 2024
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will not share