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

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1/2, Open-label, Dose-escalation, and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Therapeutic Activity of GI-101 as a Single Agent and in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Patients With Advanced or Metastatic Solid Tumors (Keynote B59)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04977453
• Other study ID #: GII-101-P101 (MK-3475-B59)
• Secondary ID: KEYNOTE-B59
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 2, 2021
• Est. completion date: October 2026

Study information

• Verified date: February 2024
• Source: GI Innovation, Inc.
• Contact: Recruiting sites have contact information. Please contact the si
• Phone: +82-2-404-2003
• Email: clinical[@]gi-innovation.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 430
• Est. completion date: October 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma
• Carcinoma, Merkel Cell
• Carcinoma, Squamous Cell
• Cervical Cancer
• Colorectal Neoplasms
• Esophageal Squamous Cell Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Melanoma
• Merkel Cell Carcinoma
• Metastatic Solid Tumor
• Microsatellite Stable Colorectal Carcinoma
• Neoplasms
• Non-small Cell Lung Cancer
• Renal Cell Carcinoma
• Sarcoma
• Squamous Cell Carcinoma of Head and Neck
• Urinary Bladder Cancer
• Urinary Bladder Neoplasms
• Vaginal Cancer
• Vaginal Neoplasms
• Vulvar Cancer
• Vulvar Neoplasms

Intervention

Drug:
• GI-101
Recommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
• Pembrolizumab (KEYTRUDA®)
Pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.
• Lenvatinib
Lenvatinib will be administered at an approved dose orally.

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

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

Locations

Country	Name	City	State
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul	Seongbuk-gu
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea St. Vincent's Hospital	Suwon-si	Kyeonggi-do
United States	Carolina Biooncology Institute	Huntersville	North Carolina
United States	Tisch Cancer Institute (TCI), Icahn School of Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
GI Innovation, Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of anti-GI-101/GI-101A antibody (ADA) and neutralizing antibody (Nab)	Serum will be assessed for the presence of ADA and Nab based on the appropriate assay.	Study Day 1, assessed up to approximately 24 months
Other	Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points	Peripheral immune cell subpopulation (e.g., CD4+ T cells, CD8+ T cells, regulatory T cells) will be assessed.	Study Day 1, assessed up to approximately 24 months
Primary	Incidence and nature of Dose-Limiting Toxicity (DLTs)	Based on toxicities observed.	Study Day 1, assessed up to approximately 24 months
Primary	Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)	Based on toxicities observed.	Study Day 1, assessed up to approximately 24 months
Primary	Objective Response Rate (ORR) according to RECIST version 1.1	Based on Investigator review of radiographic imaging.	Study Day 1, assessed up to approximately 24 months
Secondary	Peak plasma concentration (Cmax) of GI-101/GI-101A	Based on the concentration vs time profile by dose level	Study Day 1, assessed up to approximately 24 months
Secondary	Half-life of GI-101/GI-101A (T1/2)	Based on the concentration vs time profile by dose level	Study Day 1, assessed up to approximately 24 months
Secondary	Area under the plasma concentration versus time curve (AUC) of GI-101/GI-101A	Based on the concentration vs time profile by dose level	Study Day 1, assessed up to approximately 24 months
Secondary	Disease control rate (DCR) according to RECIST version 1.1	Based on Investigator review of radiographic imaging.	Study Day 1, assessed up to approximately 24 months
Secondary	Duration of objective Response (DoR) according to RECIST version 1.1	Based on Investigator review of radiographic imaging.	Study Day 1, assessed up to approximately 24 months
Secondary	Time to Tumor Response (TTR) according to RECIST version 1.1	Based on Investigator review of radiographic imaging.	Study Day 1, assessed up to approximately 24 months
Secondary	Progression-Free Survival (PFS) according to RECIST version 1.1	Based on Investigator review of radiographic imaging.	Study Day 1, assessed up to approximately 24 months
Secondary	ORR per iRECIST guidelines	Based on Investigator review of radiographic imaging.	Study Day 1, assessed up to approximately 24 months
Secondary	DCR per iRECIST guidelines	Based on Investigator review of radiographic imaging.	Study Day 1, assessed up to approximately 24 months