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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
317
Recommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
Pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.
Lenvatinib will be administered at an approved dose orally.
Recommended phase 2 dose of GI-101A will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
Tisch Cancer Institute (TCI), Icahn School of Medicine
New York, New York, United States
RECRUITINGCarolina Biooncology Institute
Huntersville, North Carolina, United States
RECRUITINGChungnam National University Hospital
Daejeon, Daejeon, South Korea
RECRUITINGThe Catholic University of Korea St. Vincent's Hospital
Suwon, Kyeonggi-do, South Korea
RECRUITINGKorea University Anam Hospital
Seoul, Seongbuk-gu, South Korea
RECRUITINGYonsei University Health System, Severance Hospital
Seoul, South Korea
RECRUITINGYonsei University Health System, Severance Hospital
Seoul, South Korea
RECRUITINGAsan Medical Center
Seoul, South Korea
RECRUITINGIncidence 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
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
Time frame: 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
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
Based on toxicities observed in Dose expansion phase of Part A, B, C, Part G1 Dose optimization cohorts and Part G2 Indication-specific cohorts
Time frame: Study Day 1, assessed up to approximately 24 months
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CONTACT
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