Advanced Solid TumorPhase 1/2NCT04977453
GI-101/GI-101A as a Single Agent or in Combination With Pembrolizumab or Lenvatinib in Advanced Solid Tumors
A Phase 1/2 study testing GI-101, Pembrolizumab (KEYTRUDA®) and Lenvatinib in people with Advanced Solid Tumor and Metastatic Solid Tumor, run by GI Innovation, Inc. at 13 sites in 2 countries.
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 or lenvatinib over a range of advanced and/or metastatic solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Metastatic Solid Tumor, Cervical Cancer
- What is being tested?
- GI-101, Pembrolizumab (KEYTRUDA®) and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 317 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 2 Aug 2021to 30 Jun 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
13 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Recruiting sites have contact information. Please contact the sites directly. contact
13 sites in 2 countries
South Korea10 sites, 10 recruiting
- Recruiting
Chungnam National University Hospital
Daejeon, Daejeon, 65015
HyoJin Lee, M.D., Ph.D.
- Recruiting
The Catholic University of Korea Seoul ST.MARY'S Hospital
Seoul, Banpo-daero, 06591
In Ho Kim
- Recruiting
Seoul National University Bundang Hospital
Seoul, Bundang-gu, 13620
EunHee Jung
- Recruiting
Samsung Medical Center
Seoul, Gangnam, 06351
Se Hoon Park
- Recruiting
Korea University Anam Hospital
Seoul, Seongbuk-gu, 02841
SooHyeon Lee, M.D.
- Recruiting
Ewha Womans University Mokdong Hospital
Seoul, Yangcheon-gu, 07985
Jeong Min Cho
- Recruiting
Yonsei University Health System, Severance Hospital
Seoul, 03722
Byoung Chul Cho, M.D., Ph.D.
Sang Joon Shin, M.D., Ph.D.
- Recruiting
Yonsei University Health System, Severance Hospital
Seoul, 03722
Jung-Yun Lee, M.D., Ph.D.
- Recruiting
Asan Medical Center
Seoul, 05505
Jae Lyun Lee, M.D., Ph.D.
- Recruiting
The Catholic University of Korea St. Vincent's Hospital
Suwon, Kyeonggi-do, 16247
Byoung-Yong Shim, M.D., Ph.D.
United States3 sites, 3 recruiting
- Recruiting
Carolina Biooncology Institute
Huntersville, North Carolina, 28078
John Powderly, M.D., Ph.D.
- Recruiting
Tisch Cancer Institute (TCI), Icahn School of Medicine
New York, New York, 10029-5674
Thomas Marron, MD, PhD
- Recruiting
Columbia University
New York, New York, 10032
Alexander Wei, M.D.
About this study
Official title: 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.
Read the 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)
- Conditions
- Advanced Solid Tumor, Metastatic Solid Tumor, Cervical Cancer, Urothelial Carcinoma, Clear Cell Renal Cell Cancer (ccRCC), Squamous Cell Non Small Cell Lung Cancer
- Being tested
- GI-101, Pembrolizumab (KEYTRUDA®), Lenvatinib, GI-101A
- Keywords
- GI-101/GI-101A, CD80-IgG4 Fc-IL2 variant, Immunotherapy, IL-2, Interleukin-2, Pembrolizumab, Lenvatinib, CPI-refractory, Immunocytokine
- Medical subject headings
- Neoplasm Metastasis, Uterine Cervical Neoplasms, Carcinoma, Transitional Cell, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GI-101Drug
Recommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
Pembrolizumab (KEYTRUDA®)Drug
Also called KEYTRUDA®
Pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.
LenvatinibDrug
Also called Lenvima®
Lenvatinib will be administered at an approved dose orally.
GI-101ADrug
Recommended phase 2 dose of GI-101A will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
| Study group | Role | What they receive |
|---|---|---|
| GI-101 | Experimental | Dose escalation: GI-101, multiple ascending doses
Dose expansion: Receives: Drug: GI-101 |
| GI-101 + Pembrolizumab | Experimental | Dose escalation: GI-101, multiple ascending doses
Dose expansion: Receives: Drug: GI-101; Drug: Pembrolizumab (KEYTRUDA®) |
| GI-101 + Lenvatinib | Experimental | Dose optimization:
Dose expansion: Receives: Drug: GI-101; Drug: Lenvatinib |
| GI-101A | Experimental | Dose escalation: GI-101A, multiple ascending doses Receives: Drug: GI-101A |
| GI-101A + Pembrolizumab | Experimental | Dose escalation: GI-101A, multiple ascending doses Dose optimization Indication-specific cohorts Receives: Drug: Pembrolizumab (KEYTRUDA®); Drug: GI-101A |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Study Day 1, assessed up to approximately 24 months
Secondary outcomes (3)
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
Measured: 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
Measured: 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
Measured: Study Day 1, assessed up to approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2021
- Study start2 Aug 2021
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 317 participants (estimated)
Sponsor and investigators
- Lead sponsor
- GI Innovation, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Nari Yun, PhD, Study director, GI Innovation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04977453
- Sponsor's protocol ID
- GII-101-P101 (MK-3475-B59)
- Other IDs
- KEYNOTE-B59
- Status last verified
- Oct 2026
- First submitted
- 9 Jul 2021
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04977453
- Acronym / sponsor ID
- GII-101-P101 (MK-3475-B59)
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 317 participants (estimated)
- Lead sponsor
- GI Innovation, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 2 Aug 2021 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 27 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| GI-101 | Experimental | Drug: GI-101Dose escalation: GI-101, multiple ascending doses Dose expansion: |
| GI-101 + Pembrolizumab | Experimental | Drug: GI-101, Drug: Pembrolizumab (KEYTRUDA®)Dose escalation: GI-101, multiple ascending doses Dose expansion: |
| GI-101 + Lenvatinib | Experimental | Drug: GI-101, Drug: LenvatinibDose optimization: Dose expansion: |
| GI-101A | Experimental | Drug: GI-101ADose escalation: GI-101A, multiple ascending doses |
| GI-101A + Pembrolizumab | Experimental | Drug: Pembrolizumab (KEYTRUDA®), Drug: GI-101ADose escalation: GI-101A, multiple ascending doses Dose optimization Indication-specific cohorts |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GI-101Recommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years). | Drug | GI-101, GI-101 + Lenvatinib, GI-101 + Pembrolizumab |
| Pembrolizumab (KEYTRUDA®)Also: KEYTRUDA®Pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W. | Drug | GI-101 + Pembrolizumab, GI-101A + Pembrolizumab |
| LenvatinibAlso: Lenvima®Lenvatinib will be administered at an approved dose orally. | Drug | GI-101 + Lenvatinib |
| GI-101ARecommended phase 2 dose of GI-101A will be administered via IV infusion Q3W up to 2 years (approximately 35 years). | Drug | GI-101A, GI-101A + Pembrolizumab |
Primary outcome
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
Dose escalation and optimization phase of Part A, B, and C and Dose escalation phase of Part E and F
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
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
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Recruiting sites have contact information. Please contact the sites directly. contact
Nari Yun, PhD study director
GI Innovation
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GI-101, Pembrolizumab (KEYTRUDA®) and Lenvatinib in people with Advanced Solid Tumor and Metastatic Solid Tumor, run by GI Innovation, Inc. at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in South Korea, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Recruiting sites have contact information. Please contact the sites directly. (+8224042003, clinical@gi-innovation.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.