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

Primary Purpose

Advanced Solid Tumor, Metastatic Solid Tumor, Non-small Cell Lung Cancer

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

GI-101

Pembrolizumab

Lenvatinib

Local Radiotherapy

GI-101A

About this trial

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring GI-101/GI-101A, CD80-IgG4 Fc-IL2 variant, Immunotherapy, IL-2, Interleukin-2, Pembrolizumab, Lenvatinib, Radiotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Tisch Cancer Institute (TCI), Icahn School of MedicineRecruiting
Carolina Biooncology InstituteRecruiting
The Catholic University of Korea St. Vincent's HospitalRecruiting
Korea University Anam HospitalRecruiting
Chungnam National University HospitalRecruiting
Yonsei University Health System, Severance HospitalRecruiting
Yonsei University Health System, Severance HospitalRecruiting
Asan Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

GI-101

GI-101 + Pembrolizumab

GI-101 + Lenvatinib

GI-101 + Local Radiotherapy

GI-101A

GI-101A + Pembrolizumab

Arm Description

Dose escalation: GI-101, multiple ascending doses Dose expansion:

Dose optimization: Dose expansion:

Dose escalation: GI-101A, multiple ascending doses Dose expansion:

Outcomes

Primary Outcome Measures

Incidence and nature of Dose-Limiting Toxicity (DLTs)

Based on toxicities observed.

Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)

Based on toxicities observed.

Objective Response Rate (ORR) according to RECIST version 1.1

Based on Investigator review of radiographic imaging.

Secondary Outcome Measures

Peak plasma concentration (Cmax) of GI-101/GI-101A

Based on the concentration vs time profile by dose level

Half-life of GI-101/GI-101A (T1/2)

Based on the concentration vs time profile by dose level

Area under the plasma concentration versus time curve (AUC) of GI-101/GI-101A

Based on the concentration vs time profile by dose level

Disease control rate (DCR) according to RECIST version 1.1

Based on Investigator review of radiographic imaging.

Duration of objective Response (DoR) according to RECIST version 1.1

Based on Investigator review of radiographic imaging.

Time to Tumor Response (TTR) according to RECIST version 1.1

Based on Investigator review of radiographic imaging.

Progression-Free Survival (PFS) according to RECIST version 1.1

Based on Investigator review of radiographic imaging.

ORR per iRECIST guidelines

Based on Investigator review of radiographic imaging.

DCR per iRECIST guidelines

Based on Investigator review of radiographic imaging.

Full Information

NCT ID

NCT04977453

First Posted

July 9, 2021

Last Updated

September 26, 2023

Sponsor

GI Innovation, Inc.

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT04977453

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 2, 2021 (Actual)

Primary Completion Date

October 2025 (Anticipated)

Study Completion Date

October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GI Innovation, Inc.

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A 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/GI-101A 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 six 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 Part E: Dose-escalation and expansion cohorts of GI-101A monotherapy Part F: Dose-escalation and expansion cohorts of GI-101A plus pembrolizumab GI-101/GI-101A 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. GI-101A is an abbreviation of advanced GI-101 with an improved formulation for manufacture consistency. Drug Information available for: Pembrolizumab (https://www.keytrudahcp.com), Lenvatinib (http://www.lenvima.com)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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, Microsatellite Stable Colorectal Carcinoma, Merkel Cell Carcinoma, Esophageal Squamous Cell Carcinoma, Cervical Cancer, Vaginal Cancer, Vulvar Cancer

Keywords

GI-101/GI-101A, CD80-IgG4 Fc-IL2 variant, Immunotherapy, IL-2, Interleukin-2, Pembrolizumab, Lenvatinib, Radiotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

430 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GI-101

Arm Type

Experimental

Arm Description

Dose escalation: GI-101, multiple ascending doses Dose expansion:

Arm Title

GI-101 + Pembrolizumab

Arm Type

Experimental

Arm Description

Dose escalation: GI-101, multiple ascending doses Dose expansion:

Arm Title

GI-101 + Lenvatinib

Arm Type

Experimental

Arm Description

Dose optimization: Dose expansion:

Arm Title

GI-101 + Local Radiotherapy

Arm Type

Experimental

Arm Description

Dose optimization: Dose expansion:

Arm Title

GI-101A

Arm Type

Experimental

Arm Description

Dose escalation: GI-101A, multiple ascending doses Dose expansion:

Arm Title

GI-101A + Pembrolizumab

Arm Type

Experimental

Arm Description

Dose escalation: GI-101A, multiple ascending doses Dose expansion:

Intervention Type

Drug

Intervention Name(s)

GI-101

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

Keytruda®

Intervention Description

Pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.

Intervention Type

Drug

Intervention Name(s)

Lenvatinib

Other Intervention Name(s)

Lenvima®

Intervention Description

Lenvatinib will be administered at an approved dose orally.

Intervention Type

Radiation

Intervention Name(s)

Local Radiotherapy

Intervention Description

Patients will receive SBRT prior to the first dose of GI-101

Intervention Type

Drug

Intervention Name(s)

GI-101A

Intervention Description

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

Primary Outcome Measure Information:

Title

Incidence and nature of Dose-Limiting Toxicity (DLTs)

Description

Based on toxicities observed.

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)

Description

Based on toxicities observed.

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Objective Response Rate (ORR) according to RECIST version 1.1

Description

Based on Investigator review of radiographic imaging.

Time Frame

Study Day 1, assessed up to approximately 24 months

Secondary Outcome Measure Information:

Title

Peak plasma concentration (Cmax) of GI-101/GI-101A

Description

Based on the concentration vs time profile by dose level

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Half-life of GI-101/GI-101A (T1/2)

Description

Based on the concentration vs time profile by dose level

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Area under the plasma concentration versus time curve (AUC) of GI-101/GI-101A

Description

Based on the concentration vs time profile by dose level

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Disease control rate (DCR) according to RECIST version 1.1

Description

Based on Investigator review of radiographic imaging.

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Duration of objective Response (DoR) according to RECIST version 1.1

Description

Based on Investigator review of radiographic imaging.

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Time to Tumor Response (TTR) according to RECIST version 1.1

Description

Based on Investigator review of radiographic imaging.

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Progression-Free Survival (PFS) according to RECIST version 1.1

Description

Based on Investigator review of radiographic imaging.

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

ORR per iRECIST guidelines

Description

Based on Investigator review of radiographic imaging.

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

DCR per iRECIST guidelines

Description

Based on Investigator review of radiographic imaging.

Time Frame

Study Day 1, assessed up to approximately 24 months

Other Pre-specified Outcome Measures:

Title

Incidence of anti-GI-101/GI-101A antibody (ADA) and neutralizing antibody (Nab)

Description

Serum will be assessed for the presence of ADA and Nab based on the appropriate assay.

Time Frame

Study Day 1, assessed up to approximately 24 months

Title

Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points

Description

Peripheral immune cell subpopulation (e.g., CD4+ T cells, CD8+ T cells, regulatory T cells) will be assessed.

Time Frame

Study Day 1, assessed up to approximately 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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. 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Recruiting sites have contact information. Please contact the sites directly.

Phone

+82-2-404-2003

clinical@gi-innovation.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nari Yun, PhD

Organizational Affiliation

GI Innovation

Official's Role

Study Director

Facility Information:

Facility Name

Tisch Cancer Institute (TCI), Icahn School of Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10029-5674

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Thomas Marron, MD, PhD

Facility Name

Carolina Biooncology Institute

City

Huntersville

State/Province

North Carolina

ZIP/Postal Code

28078

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

John Powderly, M.D., Ph.D.

Facility Name

The Catholic University of Korea St. Vincent's Hospital

City

Suwon-si

State/Province

Kyeonggi-do

ZIP/Postal Code

16247

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Byoung-Yong Shim, M.D., Ph.D.

Facility Name

Korea University Anam Hospital

City

Seoul

State/Province

Seongbuk-gu

ZIP/Postal Code

02841

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Soohyeon Lee, M.D., Ph.D.

Facility Name

Chungnam National University Hospital

City

Daejeon

ZIP/Postal Code

65015

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

HyoJin Lee, M.D., Ph.D.

Facility Name

Yonsei University Health System, Severance Hospital

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Byoung Chul Cho, M.D., Ph.D.

First Name & Middle Initial & Last Name & Degree

Sang Joon Shin, M.D., Ph.D.

Facility Name

Yonsei University Health System, Severance Hospital

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jung-Yun Lee, M.D., Ph.D.

Facility Name

Asan Medical Center

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jae Lyun Lee, M.D., Ph.D.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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