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

NCT04977453 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: GII-101-P101 (MK-3475-B59)KEYNOTE-B59
• Study Type: interventional
• Target: 317
• Locations: 2 countries
• Sites: 8

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

Conditions

Advanced Solid Tumor; Metastatic Solid Tumor; Cervical Cancer; Urothelial Carcinoma; Clear Cell Renal Cell Cancer (ccRCC); Squamous Cell Non Small Cell Lung Cancer

Keywords

GI-101/GI-101A; CD80-IgG4 Fc-IL2 variant; Immunotherapy; IL-2; Interleukin-2; Pembrolizumab; Lenvatinib; CPI-refractory; Immunocytokine

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Serum concentration of GI-101/GI-101A at specified timepoints

  Study Day 1, assessed up to approximately 24 months

• Anti-tumor activities

  Study Day 1, assessed up to approximately 24 months

• Incidence, nature, and severity of adverse events (AEs) graded according to CTCAE v5.0

  Study Day 1, assessed up to approximately 24 months

Other Outcomes (2)

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

  Study Day 1, assessed up to approximately 24 months

• 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

Study Arms (5)

GI-101

EXPERIMENTAL

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

Drug: GI-101

GI-101 + Pembrolizumab

EXPERIMENTAL

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

Drug: GI-101; Drug: Pembrolizumab (KEYTRUDA®)

GI-101 + Lenvatinib

EXPERIMENTAL

Dose optimization: Dose expansion:

Drug: GI-101; Drug: Lenvatinib

GI-101A

EXPERIMENTAL

Dose escalation: GI-101A, multiple ascending doses

Drug: GI-101A

GI-101A + Pembrolizumab

EXPERIMENTAL

Dose escalation: GI-101A, multiple ascending doses Dose optimization Indication-specific cohorts

Drug: Pembrolizumab (KEYTRUDA®); Drug: GI-101A

Interventions

GI-101 DRUG

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

GI-101; GI-101 + Lenvatinib; GI-101 + Pembrolizumab

Pembrolizumab (KEYTRUDA®) DRUG

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

Also known as: KEYTRUDA®

GI-101 + Pembrolizumab; GI-101A + Pembrolizumab

Lenvatinib DRUG

Lenvatinib will be administered at an approved dose orally.

Also known as: Lenvima®

GI-101 + Lenvatinib

GI-101A DRUG

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

GI-101A; GI-101A + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GI Innovation, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

Tisch Cancer Institute (TCI), Icahn School of Medicine

New York, New York, 10029-5674, United States

RECRUITING

Carolina Biooncology Institute

Huntersville, North Carolina, 28078, United States

RECRUITING

Chungnam National University Hospital

Daejeon, Daejeon, 65015, South Korea

RECRUITING

The Catholic University of Korea St. Vincent's Hospital

Suwon, Kyeonggi-do, 16247, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, Seongbuk-gu, 02841, South Korea

RECRUITING

Yonsei University Health System, Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Yonsei University Health System, Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Uterine Cervical Neoplasms; Carcinoma, Transitional Cell; Carcinoma, Renal Cell

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Nari Yun, PhD

  GI Innovation

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

+8224042003; clinical@gi-innovation.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: July 27, 2021
• Study Start: August 2, 2021
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (6); US (2)