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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 : August 4, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GI Innovation, Inc.

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.

Condition or disease Intervention/treatment Phase
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 Drug: GI-101 Drug: Pembrolizumab Drug: Lenvatinib Radiation: Local Radiotherapy Phase 1 Phase 2

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 374 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 23, 2021
Estimated Primary Completion Date : September 2025
Estimated Study Completion Date : December 2025


Arm Intervention/treatment
Experimental: GI-101

Dose escalation: GI-101, multiple ascending doses

Dose expansion:

Drug: GI-101
Recommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).

Experimental: GI-101 + Pembrolizumab

Dose escalation: GI-101, multiple ascending doses

Dose expansion:

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®

Experimental: GI-101 + Lenvatinib

Dose optimization:

Dose expansion:

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: Lenvatinib
Lenvatinib will be administered at an approved dose orally.
Other Name: Lenvima®

Experimental: GI-101 + Local Radiotherapy

Dose optimization:

Dose expansion:

Drug: GI-101
Recommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).

Radiation: Local Radiotherapy
Patients will receive SBRT prior to the first dose of GI-101




Primary Outcome Measures :
  1. Incidence and nature of Dose-Limiting Toxicity (DLTs) [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on toxicities observed.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. ORR per iRECIST guidelines [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.

  9. DCR per iRECIST guidelines [ Time Frame: Study Day 1, assessed up to approximately 24 months ]
    Based on Investigator review of radiographic imaging.


Other Outcome Measures:
  1. 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.

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • Leptomeningeal disease.
  • 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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04977453


Contacts
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Contact: Recruiting sites have contact information. Please contact the sites directly. +82-2-404-2003 clinical@gi-innovation.com

Locations
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Korea, Republic of
Yonsei University Health System, Severance Hospital Recruiting
Seoul, Korea, Republic of, 03722
Principal Investigator: Byoung Chul Cho, M.D., Ph.D.         
Sub-Investigator: Sang Joon Shin, M.D., Ph.D.         
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Principal Investigator: Jae Lyun Lee, M.D., Ph.D.         
Sponsors and Collaborators
GI Innovation, Inc.
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Nari Yun, PhD GI Innovation
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Responsible Party: GI Innovation, Inc.
ClinicalTrials.gov Identifier: NCT04977453    
Other Study ID Numbers: GII-101-P101 (MK-3475-B59)
KEYNOTE-B59 ( Other Identifier: Merck Sharp & Dohme Corp. )
First Posted: July 27, 2021    Key Record Dates
Last Update Posted: August 4, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GI Innovation, Inc.:
GI-101
CD80-IgG4 Fc-IL2 variant
Immunotherapy
IL-2
Interleukin-2
Pembrolizumab
Lenvatinib
Radiotherapy
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Carcinoma, Squamous Cell
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Adenocarcinoma
Kidney Neoplasms
Kidney Diseases
Head and Neck Neoplasms
Pembrolizumab
Lenvatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action