GI-101 as a Single Agent or in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Advanced Solid Tumors
- Conditions
- Cervical CancerVaginal CancerRenal Cell CarcinomaMelanomaSarcomaMicrosatellite Stable Colorectal CarcinomaEsophageal Squamous Cell CarcinomaVulvar CancerAdvanced Solid TumorNon-small Cell Lung Cancer
- Interventions
- Radiation: Local Radiotherapy
- Registration Number
- NCT04977453
- Lead Sponsor
- GI Innovation, Inc.
- 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, lenvatinib or local radiotherapy (RT) over a range of advanced and/or metastatic solid tumors.
- Detailed Description
This is a phase 1/2, open-label, dose-escalation and expansion study to evaluate the safety, tolerability and anti-tumor effect of GI-101/GI-101A as a single agent or in combination with pembrolizumab, lenvatinib or local RT over a range of advanced and/or metastatic solid tumors.
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 D: Dose-optimization and expansion cohorts of GI-101 plus local RT
* Part E: Dose-escalation and expansion cohorts of GI-101A monotherapy
* Part F: Dose-escalation and expansion cohorts of GI-101A plus pembrolizumab
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)
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 430
- 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
- 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 (except Part D).
- 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, pembrolizumab or lenvatinib.
Other protocol defined inclusion exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description GI-101 + Local Radiotherapy Local Radiotherapy Dose optimization: Dose expansion: GI-101A + Pembrolizumab Pembrolizumab (KEYTRUDA®) Dose escalation: GI-101A, multiple ascending doses Dose expansion: GI-101 + Pembrolizumab Pembrolizumab (KEYTRUDA®) Dose escalation: GI-101, multiple ascending doses Dose expansion: GI-101A + Pembrolizumab GI-101A Dose escalation: GI-101A, multiple ascending doses Dose expansion: GI-101A GI-101A Dose escalation: GI-101A, multiple ascending doses Dose expansion: GI-101 + Lenvatinib Lenvatinib Dose optimization: Dose expansion: GI-101 + Pembrolizumab GI-101 Dose escalation: GI-101, multiple ascending doses Dose expansion: GI-101 GI-101 Dose escalation: GI-101, multiple ascending doses Dose expansion: GI-101 + Lenvatinib GI-101 Dose optimization: Dose expansion: GI-101 + Local Radiotherapy GI-101 Dose optimization: Dose expansion:
- Primary Outcome Measures
Name Time Method Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) Study Day 1, assessed up to approximately 24 months Based on toxicities observed.
Objective Response Rate (ORR) according to RECIST version 1.1 Study Day 1, assessed up to approximately 24 months Based on Investigator review of radiographic imaging.
Incidence and nature of Dose-Limiting Toxicity (DLTs) Study Day 1, assessed up to approximately 24 months Based on toxicities observed.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) according to RECIST version 1.1 Study Day 1, assessed up to approximately 24 months Based on Investigator review of radiographic imaging.
Duration of objective Response (DoR) according to RECIST version 1.1 Study Day 1, assessed up to approximately 24 months Based on Investigator review of radiographic imaging.
DCR per iRECIST guidelines Study Day 1, assessed up to approximately 24 months Based on Investigator review of radiographic imaging.
Half-life of GI-101/GI-101A (T1/2) Study Day 1, assessed up to approximately 24 months Based on the concentration vs time profile by dose level
Disease control rate (DCR) according to RECIST version 1.1 Study Day 1, assessed up to approximately 24 months Based on Investigator review of radiographic imaging.
Peak plasma concentration (Cmax) of GI-101/GI-101A Study Day 1, assessed up to approximately 24 months Based on the concentration vs time profile by dose level
Area under the plasma concentration versus time curve (AUC) of GI-101/GI-101A Study Day 1, assessed up to approximately 24 months Based on the concentration vs time profile by dose level
Time to Tumor Response (TTR) according to RECIST version 1.1 Study Day 1, assessed up to approximately 24 months Based on Investigator review of radiographic imaging.
ORR per iRECIST guidelines Study Day 1, assessed up to approximately 24 months Based on Investigator review of radiographic imaging.
Trial Locations
- Locations (7)
Tisch Cancer Institute (TCI), Icahn School of Medicine
🇺🇸New York, New York, United States
Carolina Biooncology Institute
🇺🇸Huntersville, North Carolina, United States
The Catholic University of Korea St. Vincent's Hospital
🇰🇷Suwon-si, Kyeonggi-do, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Seongbuk-gu, Korea, Republic of
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Yonsei University Health System, Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of