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

Sponsor

GI Innovation, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04977453

Collaborator

Merck Sharp & Dohme LLC (Industry)

374

Enrollment

Locations

Arms

37.3

Anticipated Duration (Months)

93.5

Patients Per Site

2.5

Patients Per Site Per Month

Study Details

Study Description

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)

Study Design

Study Type:

Interventional

Anticipated 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 :

Jul 23, 2021

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

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 Names: 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 Names: 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

Outcome Measures

Primary Outcome Measures

Incidence and nature of Dose-Limiting Toxicity (DLTs) [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) [Study Day 1, assessed up to approximately 24 months]
Based on toxicities observed.
Objective Response Rate (ORR) according to RECIST version 1.1 [Study Day 1, assessed up to approximately 24 months]
Based on Investigator review of radiographic imaging.

Secondary Outcome Measures

Peak plasma concentration (Cmax) of GI-101 [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) [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 [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 [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 [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 [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 [Study Day 1, assessed up to approximately 24 months]
Based on Investigator review of radiographic imaging.
ORR per iRECIST guidelines [Study Day 1, assessed up to approximately 24 months]
Based on Investigator review of radiographic imaging.
DCR per iRECIST guidelines [Study Day 1, assessed up to approximately 24 months]
Based on Investigator review of radiographic imaging.

Other Outcome Measures

Incidence of anti-GI-101 antibody (ADA) and neutralizing antibody (Nab) [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Catholic University of Korea St. Vincent's Hospital	Suwon-si	Kyeonggi-do	Korea, Republic of	16247
2	Chungnam National University Hospital	Daejeon		Korea, Republic of	65015
3	Yonsei University Health System, Severance Hospital	Seoul		Korea, Republic of	03722
4	Asan Medical Center	Seoul		Korea, Republic of	05505