GI-101/GI-101A as a Single Agent or in Combination With Pembrolizumab or Lenvatinib in Advanced Solid Tumors

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

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 or lenvatinib over a range of advanced and/or metastatic solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Advanced Solid Tumor; Metastatic Solid Tumor; Urothelial Carcinoma; Squamous Cell Non Small Cell Lung Cancer; Clear Cell Renal Cell Cancer (ccRCC)
• Intervention / Treatment: Drug: GI-101; Drug: Lenvatinib; Drug: GI-101A; Drug: Pembrolizumab (KEYTRUDA®)

Detailed Description

This is a Phase 1/2, open-label, dose-escalation, dose-optimization and expansion study to evaluate safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent and in combination with pembrolizumab or lenvatinib in patients with advanced or metastatic solid tumors (Keynote B59)

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 E: Dose-escalation cohorts of GI-101A monotherapy
• Part F: Dose-escalation cohorts of GI-101A plus pembrolizumab

• Part G: Dose-optimization and indication-specific cohorts of GI-101A plus pembrolizumab

  • Part G1: Dose optimization cohorts in CPI-refractory urothelial cancer
  • Part G2: Indication-specific cohorts in CPI-refractory ccRCC, squamous cell NSCLC and SoC-experienced MSS/pMMR CRC

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)

• Study Type: Interventional
• Enrollment (Estimated): 317
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Recruiting sites have contact information. Please contact the sites directly.; Phone Number: +8224042003; Email: clinical@gi-innovation.com

Study Locations

• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
    • Principal Investigator: Jae Lyun Lee, M.D., Ph.D.
  • Seoul, South Korea, 03722
    • Recruiting
    • Yonsei University Health System, Severance Hospital
    • Principal Investigator: Jung-Yun Lee, M.D., Ph.D.
  • Banpo-daero
    • Seoul, Banpo-daero, South Korea, 06591
      • Recruiting
      • The Catholic University of Korea Seoul St.Mary's Hospital
      • Principal Investigator: In Ho Kim
  • Bundang-gu
    • Seoul, Bundang-gu, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
      • Principal Investigator: EunHee Jung
  • Daejeon
    • Daejeon, Daejeon, South Korea, 65015
      • Recruiting
      • Chungnam national university hospital
      • Principal Investigator: HyoJin Lee, M.D., Ph.D.
  • Gangnam
    • Seoul, Gangnam, South Korea, 06351
      • Recruiting
      • Samsung Medical Center
      • Principal Investigator: Se Hoon Park
  • Kyeonggi-do
    • Suwon, Kyeonggi-do, South Korea, 16247
      • Recruiting
      • The Catholic University Of Korea St. Vincent's Hospital
      • Principal Investigator: Byoung-Yong Shim, M.D., Ph.D.
  • Seongbuk-gu
    • Seoul, Seongbuk-gu, South Korea, 02841
      • Recruiting
      • Korea University Anam Hospital
      • Principal Investigator: SooHyeon Lee, M.D.
  • Yangcheon-gu
    • Seoul, Yangcheon-gu, South Korea, 07985
      • Recruiting
      • Ewha Womans University Mokdong Hospital
      • Principal Investigator: Jeong Min Cho
• United States
  • New York
    • New York, New York, United States, 10029-5674
      • Recruiting
      • Tisch Cancer Institute (TCI), Icahn School of Medicine
      • Principal Investigator: Thomas Marron, MD, PhD
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • Carolina BioOncology Institute
      • Principal Investigator: John Powderly, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• 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/GI-101A, pembrolizumab or lenvatinib.

Other protocol defined inclusion exclusion criteria may apply. Cancer type and part-specific inclusion criteria are described in the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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 (KEYTRUDA®); 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-101A; Dose escalation: GI-101A, multiple ascending doses	Drug: GI-101A; Recommended phase 2 dose of GI-101A will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
Experimental: GI-101A + Pembrolizumab; Dose escalation: GI-101A, multiple ascending doses Dose optimization Indication-specific cohorts	Drug: GI-101A; Recommended phase 2 dose of GI-101A will be administered via IV infusion Q3W up to 2 years (approximately 35 years).; Drug: Pembrolizumab (KEYTRUDA®); Pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.; Other Names: KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and nature of Dose-Limiting Toxicity (DLTs), Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)	Dose escalation and optimization phase of Part A, B, and C and Dose escalation phase of Part E and F	Study Day 1, assessed up to approximately 24 months
Objective Response Rate (ORR), Disease Control Rate (DCR) and Duration of Response (DoR) according to RECIST version 1.1	Based on Central review (Part G1) and Investigator review (Part G2) of radiographic imaging in Part G1 Dose optimization cohorts, Part G2 Indication-specific cohorts ORR only; Based on Investigator review of radiographic imaging in dose expansion phase of Part A, B and C	Study Day 1, assessed up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentration of GI-101/GI-101A at specified timepoints	Serum concentration of GI-101/GI-101A at specified timepoints for the following parameters including but not limited to Cmax, Tmax, AUC0-last, AUC0-inf, T1/2, CL, Vd etc. Based on the concentration vs time profile by dose level in Dose escalation and optimization phase of Part A, B, C, E, and Part F and Dose expansion of Part A, B and C, Part G1 Dose optimization cohorts, Part G2 Indication-specific cohorts	Study Day 1, assessed up to approximately 24 months
Anti-tumor activities	Anti-tumor activities, including but not limited to Overall response Rate, Disease Control Rate, Duration of Response, Time to Tumor Response, Progression-free survival, according to RECIST version 1.1, Overall survival. Based on Investigator review of radiographic imaging in Dose escalation and optimization phase of Part A, B, C, E, and Part F, Dose expansion of Part A, B and C, Part G1 Dose optimization cohorts, Part G2 Indication-specific cohorts	Study Day 1, assessed up to approximately 24 months
Incidence, nature, and severity of adverse events (AEs) graded according to CTCAE v5.0	Based on toxicities observed in Dose expansion phase of Part A, B, C, Part G1 Dose optimization cohorts and Part G2 Indication-specific cohorts	Study Day 1, assessed up to approximately 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: GI Innovation, Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Nari Yun, PhD, GI Innovation

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2021
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: July 26, 2021
• First Posted (Actual): July 27, 2021

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Pembrolizumab; Lenvatinib; IL-2; Interleukin-2; Immunocytokine; CD80-IgG4 Fc-IL2 variant; GI-101/GI-101A; CPI-refractory
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neoplastic Processes; Genital Neoplasms, Female; Urologic Neoplasms; Carcinoma; Uterine Cervical Diseases; Kidney Neoplasms; Uterine Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Carcinoma, Renal Cell; Uterine Cervical Neoplasms; Carcinoma, Transitional Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; pembrolizumab; lenvatinib
• Other Study ID Numbers: GII-101-P101 (MK-3475-B59); KEYNOTE-B59 (Other Identifier: Merck Sharpe and Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No