RecruitingInterventionalPhase 1/Phase 2

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)

NCT ID: NCT04977453Sponsor: GI Innovation, Inc.Last updated: 2026-05-15

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.

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)

Arms & interventions

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

Outcome measures

Primary

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
Time frame: 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
Time frame: Study Day 1, assessed up to approximately 24 months

Secondary

Serum concentration of GI-101/GI-101A at specified timepoints
Time frame: Study Day 1, assessed up to approximately 24 months
Anti-tumor activities
Time frame: Study Day 1, assessed up to approximately 24 months
Incidence, nature, and severity of adverse events (AEs) graded according to CTCAE v5.0
Time frame: Study Day 1, assessed up to approximately 24 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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 locations (2)

Tisch Cancer Institute (TCI), Icahn School of Medicine

New York, New York, 10029-5674

Recruiting

Thomas Marron, MD, PhD · Principal Investigator

Carolina Biooncology Institute

Huntersville, North Carolina, 28078

Recruiting

John Powderly, M.D., Ph.D. · Principal Investigator