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)

NCT05824975
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
358
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Lead sponsor
GI Innovation, Inc.
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Start date
2023-05-30
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Number of sites
11
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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.
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Short title
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)
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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-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)
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2027-04-24
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First posted
2023-04-24
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Registry last updated
2024-11-25
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Primary completion date
2025-11-12
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Start date
2023-05-30
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Participants
358
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Participant count basis
Estimated
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Planned participants
358
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Protocol amendments
1
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Number of sites
11
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
GI Innovation, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05824975
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ClinicalTrials.gov ID
NCT05824975
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Incidence and nature of Dose-Limiting Toxicity (DLTs) (dose escalation phase of Part A and B)

    Timeframe: Study Day 1, assessed up to DLT period (3 weeks after treatment)

    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.

  2. Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) (dose escalation phase of Part A and B)

    Timeframe: Study Day 1, assessed up to approximately 24 months

    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.

  3. Objective Response Rate (ORR) (dose optimization phase of Part A, dose expansion phase of Part B, Part C and D)

    Timeframe: Study Day 1, assessed up to approximately 24 months

    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).

  1. Objective Response Rate (ORR) (dose escalation phase of Part A and B)

    Timeframe: Study Day 1, assessed up to approximately 24 months

    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).

  2. Incidence and nature of Dose-Limiting Toxicity (DLTs) (dose optimization phase of Part A, dose expansion phase of Part B, Part C and D)

    Timeframe: Study Day 1, assessed up to DLT period (3 weeks after treatment)

    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.

  3. 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)

    Timeframe: Study Day 1, assessed up to approximately 24 months

    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.

  4. Disease Control Rate (DCR)

    Timeframe: Study Day 1, assessed up to approximately 24 months

    DCR is defined as the percentage of patients who have achieved CR, PR and stable disease (SD), per RECIST v1.1 guideline as determined by the investigators.

  5. Duration of objective response (DoR)

    Timeframe: Study Day 1, assessed up to approximately 24 months

    DCR is defined as the time from the first occurrence of a documented objective response to the time of the first document disease progression or death from any cause, whichever occurs first, per RECIST v1.1 as determined by the investigator.

  6. Progression-free survival (PFS)

    Timeframe: 6-month, 12-month, and 18-month

    PFS is defined as the time from the first study treatment (Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per RECIST v1.1 guideline as determined by the investigator

  7. Overall survival (OS)

    Timeframe: 12-month and 18-month

    OS is defined as the time from the first study treatment to death from any cause

  8. Peak plasma concentration (Cmax) of GI-102

    Timeframe: Study Day 1, assessed up to approximately 24 months

    Based on the concentration vs time profile by dose level

  9. Half-life of GI-102 (T1/2)

    Timeframe: Study Day 1, assessed up to approximately 24 months

    Based on the concentration vs time profile by dose level

  10. Area under the plasma concentration versus time curve (AUC) of GI-102

    Timeframe: Study Day 1, assessed up to approximately 24 months

    Based on the concentration vs time profile by dose level

  11. Clearance of GI-102

    Timeframe: Study Day 1, assessed up to approximately 24 months

    Based on the concentration vs time profile by dose level

  12. Volume of distribution (Vd) of GI-102 after administration

    Timeframe: Study Day 1, assessed up to approximately 24 months

    Based on the concentration vs time profile by dose level

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

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

Sources for eligibility
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  • Mayo Clinic in ArizonaScottsdale, United StatesRecruiting
  • Mayo Clinic in FloridaJacksonville, United StatesRecruiting
  • Mayo Clinic in MinnesotaRochester, United StatesRecruiting
  • Memorial Sloan-Kettering Cancer CenterNew York, United StatesRecruiting
  • Cleveland ClinicCleveland, United StatesRecruiting
  • Seoul National University HospitalSeoul, South KoreaRecruiting
  • St. Vincent's HospitalSuwon, South KoreaRecruiting
  • Yonsei University Health System, Severance HospitalSeoul, South KoreaRecruiting
  • Yonsei University Health System, Severance HospitalSeoul, South KoreaRecruiting
  • Asan Medical CenterSeoul, South KoreaRecruiting
  • Samsung Medical CenterSeoul, South KoreaRecruiting
Sources for sites
clinicaltrials.gov

Related records

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