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.
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.
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
Sequential
GI-101
DrugRecommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
Pembrolizumab (KEYTRUDA®)
DrugPembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.
Lenvatinib
DrugLenvatinib will be administered at an approved dose orally.
GI-101A
DrugRecommended phase 2 dose of GI-101A will be administered via IV infusion Q3W up to 2 years (approximately 35 years).
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
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
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
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
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
Incidence of anti-GI-101/GI-101A antibody (ADA) and neutralizing antibody (Nab)
Serum will be assessed for the presence of ADA and Nab based on the appropriate assay.
Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points
Peripheral immune cell subpopulation (e.g., CD4+ T cells, CD8+ T cells, regulatory T cells) will be assessed.
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GI Innovation, Inc.
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
