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GI-101 as a Single Agent or in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04977453
Recruitment Status : Recruiting
First Posted : July 27, 2021
Last Update Posted : November 5, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GI Innovation, Inc.

Tracking Information
First Submitted Date  ICMJE July 9, 2021
First Posted Date  ICMJE July 27, 2021
Last Update Posted Date November 5, 2021
Actual Study Start Date  ICMJE July 23, 2021
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2021)
  • Incidence and nature of Dose-Limiting Toxicity (DLTs) [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on toxicities observed.
  • Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on toxicities observed.
  • Objective Response Rate (ORR) according to RECIST version 1.1 [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2021)
  • Peak plasma concentration (Cmax) of GI-101 [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on the concentration vs time profile by dose level
  • Half-life of GI-101 (T1/2) [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on the concentration vs time profile by dose level
  • Area under the plasma concentration versus time curve (AUC) of GI-101 [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on the concentration vs time profile by dose level
  • Disease control rate (DCR) according to RECIST version 1.1 [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.
  • Duration of objective Response (DoR) according to RECIST version 1.1 [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.
  • Time to Tumor Response (TTR) according to RECIST version 1.1 [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.
  • Progression-Free Survival (PFS) according to RECIST version 1.1 [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.
  • ORR per iRECIST guidelines [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.
  • DCR per iRECIST guidelines [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 26, 2021)
  • Incidence of anti-GI-101 antibody (ADA) and neutralizing antibody (Nab) [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Serum will be assessed for the presence of ADA and Nab based on the appropriate assay.
  • Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Peripheral immune cell subpopulation (e.g., CD4+ T cells, CD8+ T cells, regulatory T cells) will be assessed.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE GI-101 as a Single Agent or in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Advanced Solid Tumors
Official Title  ICMJE A Phase 1/2 Study to Evaluate Safety, Tolerability, PK, and Therapeutic Activity of GI-101 as a Single Agent and in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Patients With Advanced, Metastatic Solid Tumors
Brief Summary The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101 as a single agent or in combination with pembrolizumab, lenvatinib or local radiotherapy (RT) over a range of advanced and/or metastatic solid tumors.
Detailed Description

This is a phase 1/2, open-label, dose-escalation and expansion study to evaluate the safety, tolerability and anti-tumor effect of GI-101 as a single agent or in combination with pembrolizumab, lenvatinib or local RT over a range of advanced and/or metastatic solid tumors.

This study will comprise four parts.

  • Part A: Dose-escalation and expansion cohorts of GI-101 monotherapy
  • Part B: Dose-escalation and expansion cohorts of GI-101 plus pembrolizumab
  • Part C: Dose-optimization and expansion cohorts of GI-101 plus lenvatinib
  • Part D: Dose-optimization and expansion cohorts of GI-101 plus local RT

GI-101 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.

Drug Information available for: Pembrolizumab (https://www.keytrudahcp.com), Lenvatinib (http://www.lenvima.com)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumor
  • Metastatic Solid Tumor
  • Non-small Cell Lung Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Renal Cell Carcinoma
  • Urinary Bladder Cancer
  • Melanoma
  • Sarcoma
Intervention  ICMJE
  • Drug: GI-101
    Recommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
  • Drug: Pembrolizumab
    Pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.
    Other Name: Keytruda®
  • Drug: Lenvatinib
    Lenvatinib will be administered at an approved dose orally.
    Other Name: Lenvima®
  • Radiation: Local Radiotherapy
    Patients will receive SBRT prior to the first dose of GI-101
Study Arms  ICMJE
  • Experimental: GI-101

    Dose escalation: GI-101, multiple ascending doses

    Dose expansion:

    Intervention: Drug: GI-101
  • Experimental: GI-101 + Pembrolizumab

    Dose escalation: GI-101, multiple ascending doses

    Dose expansion:

    Interventions:
    • Drug: GI-101
    • Drug: Pembrolizumab
  • Experimental: GI-101 + Lenvatinib

    Dose optimization:

    Dose expansion:

    Interventions:
    • Drug: GI-101
    • Drug: Lenvatinib
  • Experimental: GI-101 + Local Radiotherapy

    Dose optimization:

    Dose expansion:

    Interventions:
    • Drug: GI-101
    • Radiation: Local Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 26, 2021)
374
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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-101.
  • 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 (except Part D).
  • 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-101, pembrolizumab or lenvatinib.

Other protocol defined inclusion exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Recruiting sites have contact information. Please contact the sites directly. +82-2-404-2003 clinical@gi-innovation.com
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04977453
Other Study ID Numbers  ICMJE GII-101-P101 (MK-3475-B59)
KEYNOTE-B59 ( Other Identifier: Merck Sharp & Dohme Corp. )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party GI Innovation, Inc.
Study Sponsor  ICMJE GI Innovation, Inc.
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Nari Yun, PhD GI Innovation
PRS Account GI Innovation, Inc.
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP