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)
Overview
- Phase
- Phase 1
- Intervention
- GI-101
- Conditions
- Advanced Solid Tumor
- Sponsor
- GI Innovation, Inc.
- Enrollment
- 317
- Locations
- 9
- Primary Endpoint
- Incidence and nature of Dose-Limiting Toxicity (DLTs), Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)
- Status
- Recruiting
- Last Updated
- last month
Overview
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)
Investigators
Eligibility Criteria
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.
- •ECOG performance status 0-
- •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.
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-
- •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
- •Administration of prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
Arms & Interventions
GI-101
Dose escalation: GI-101, multiple ascending doses Dose expansion:
Intervention: GI-101
GI-101 + Pembrolizumab
Dose escalation: GI-101, multiple ascending doses Dose expansion:
Intervention: GI-101
GI-101 + Pembrolizumab
Dose escalation: GI-101, multiple ascending doses Dose expansion:
Intervention: Pembrolizumab (KEYTRUDA®)
GI-101 + Lenvatinib
Dose optimization: Dose expansion:
Intervention: GI-101
GI-101 + Lenvatinib
Dose optimization: Dose expansion:
Intervention: Lenvatinib
GI-101A
Dose escalation: GI-101A, multiple ascending doses
Intervention: GI-101A
GI-101A + Pembrolizumab
Dose escalation: GI-101A, multiple ascending doses Dose optimization Indication-specific cohorts
Intervention: Pembrolizumab (KEYTRUDA®)
GI-101A + Pembrolizumab
Dose escalation: GI-101A, multiple ascending doses Dose optimization Indication-specific cohorts
Intervention: GI-101A
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Serum concentration of GI-101/GI-101A at specified timepoints(Study Day 1, assessed up to approximately 24 months)
- Anti-tumor activities(Study Day 1, assessed up to approximately 24 months)
- Incidence, nature, and severity of adverse events (AEs) graded according to CTCAE v5.0(Study Day 1, assessed up to approximately 24 months)