Recruiting
Phase 1
Phase 2

GI-101, Pembrolizumab, Lenvatinib, RT

Sponsor:

GI Innovation, Inc.

Code:

NCT04977453

Conditions

Advanced Solid Tumor

Metastatic Solid Tumor

Cervical Cancer

Urothelial Carcinoma

Clear Cell Renal Cell Cancer (ccRCC)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

GI-101

Pembrolizumab (KEYTRUDA®)

Lenvatinib

GI-101A

Study Details

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)

Study ID

NCT04977453

Start date

Aug 2, 2021

Status verified date

Mar, 2026

Completion date

Jun 30, 2028

Anticipated

Primary completion date

Jun 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

317 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: GI-101

Dose escalation: GI-101, multiple ascending doses

Dose expansion:

experimental: GI-101 + Pembrolizumab

Dose escalation: GI-101, multiple ascending doses

Dose expansion:

experimental: GI-101 + Lenvatinib

Dose optimization:

Dose expansion:

experimental: GI-101A

Dose escalation: GI-101A, multiple ascending doses

experimental: GI-101A + Pembrolizumab

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

Interventions

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.

GI-101A

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

Primary outcome measure

  • Incidence and nature of Dose-Limiting Toxicity (DLTs), Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) [ 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 [ Time Frame: Study Day 1, assessed up to approximately 24 months ]

Central Contacts and Locations

Central contacts

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

+8224042003clinical@gi-innovation.com

Locations

Tisch Cancer Institute (TCI), Icahn School of Medicine

Recruiting

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

Principal Investigator:

Thomas Marron, MD, PhD

Carolina Biooncology Institute

Recruiting

Huntersville, North Carolina, United States, 28078

Principal Investigator:

John Powderly, M.D., Ph.D.

More Information

Sponsor

GI Innovation, Inc.

Last update posted

May 15, 2026

Last verified

Mar, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by GI Innovation, Inc. on 2026-05-15.