Advanced Solid Tumor, Cervical Cancer, Clear Cell Renal Cell Cancer (ccRCC), Metastatic Solid Tumor, Squamous Cell Non Small Cell Lung Cancer, Urothelial Carcinoma
Conditions
Keywords
GI-101/GI-101A, CD80-IgG4 Fc-IL2 variant, Immunotherapy, IL-2, Interleukin-2, Pembrolizumab, Lenvatinib, CPI-refractory, Immunocytokine
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.
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)
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).
Sponsors
GI Innovation, Inc.
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and nature of Dose-Limiting Toxicity (DLTs), Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum concentration of GI-101/GI-101A at specified timepoints | Study Day 1, assessed up to approximately 24 months | 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 |
| Anti-tumor activities | Study Day 1, assessed up to approximately 24 months | 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 |
| Incidence, nature, and severity of adverse events (AEs) graded according to CTCAE v5.0 | Study Day 1, assessed up to approximately 24 months | Based on toxicities observed in Dose expansion phase of Part A, B, C, Part G1 Dose optimization cohorts and Part G2 Indication-specific cohorts |
Countries
South Korea, United States
Contacts
CONTACTRecruiting sites have contact information. Please contact the sites directly.
STUDY_DIRECTORNari Yun, PhD
GI Innovation
Outcome results
None listed