The goal of this clinical trial is to determine the most effective dose of EIK1005 that a person can take safely. Additionally, this study will test how well EIK1005 is tolerated alone and in combination with pembrolizumab in treating patients with advanced cancer.
This Phase 1/2 study (EIK1005-002) will investigate the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of EIK1005 as a monotherapy and in combination with pembrolizumab in participants with advanced solid tumors, including participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Tumors. The study will be conducted in 2 parts: Part 1 and Part 2, with Part 1 being further divided into Part 1A and Part 1B as described below: * Part 1A (monotherapy dose escalation): participants will receive EIK1005 only. * Part 1B (combination dose escalation): participants will receive EIK1005 in combination with pembrolizumab. * Part 2 (dose optimization): participants will be randomized 1:1 to monotherapy with EIK1005 at one of the two selected doses from Part 1A to identify the dose of EIK1005 in monotherapy for subsequent studies.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
EIK1005 is a selective inhibitor of the Werner helicase.
Pembrolizumab is a PD-1 inhibitor.
Morristown Medical Center
Morristown, New Jersey, United States
Memorial Sloan Kettering Cancer Center (MSKCC)
New York, New York, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Calvary Mater Newcastle Hospital
Waratah, New South Wales, Australia
Illawarra Cancer Care Centre (ICCC)
Wollongong, New South Wales, Australia
Chris O'Brien Lifehouse (Sydney Cancer Centre)
Camperdown, Victoria, Australia
Peninsula and Southeast Oncology (PASO) Medical
Frankston, Victoria, Australia
Olivia Newton John Cancer Research Institute
Heidelberg, Victoria, Australia
Dose-Limiting Toxicity (DLT) - Part 1
A DLT is a protocol-defined adverse event occurring during the DLT observation period.
Time frame: 21 Days
Adverse Events (AEs) - Part 1 and Part 2
Number of participants reporting adverse events or serious adverse events.
Time frame: From the time of first dose of study medication through 30 days following cessation of study treatment.
Objective Response (OR) - Part 1 and Part 2
OR defined as participants who have a complete response \[CR\] or partial response \[PR\] by Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1 as assessed by the Investigator.
Time frame: Through study completion, an average of 2 years.
Duration of Response (DOR) - Part 1 and Part 2
DOR (defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first, in participants demonstrating CR or PR) by RECIST 1.1 as assessed by the Investigator.
Time frame: Through study completion, an average of 2 years.
Disease Control (DC) - Part 1 and Part 2
DC defined as participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) by RECIST 1.1 as assessed by the Investigator.
Time frame: Through study completion, an average of 2 years.
Progression-free survival (PFS) - Part 2
PFS defined as the time from randomization to the first documented disease progression by RECIST 1.1 as assessed by the Investigator or death due to any cause, whichever occurs first.
Time frame: Through study completion, an average of 2 years.
Pharmacokinetic (PK) parameters of EIK1005 - AUC0-24 (Part 1 and Part 2)
AUC0-24 (Area Under the plasma Concentration versus time curve from 0 to 24 hours): Measures total drug exposure over the first 24 hours after dosing of EIK1005 as monotherapy and in combination with pembrolizumab.
Time frame: Up to 1 year
Pharmacokinetic (PK) parameters of EIK1005 - AUCtau,ss (Part 1 and Part 2)
AUCtau,ss \[Area Under the plasma Concentration versus time curve over one dosing interval (tau) at steady state\]: Reflects average drug exposure during each dosing interval once the steady state has been reached for EIK1005 as monotherapy and in combination with pembrolizumab.
Time frame: Up to 1 year
Pharmacokinetic (PK) parameters of EIK1005 - Cmax (Part 1 and Part 2)
Cmax (Maximum Plasma Concentration) after dose administration of EIK1005 as monotherapy and in combination with pembrolizumab.
Time frame: Up to 1 year
Pharmacokinetic (PK) parameters of EIK1005 - tmax (Part 1 and Part 2)
tmax (the time required for the plasma concentration of the drug to reach maximum concentration after dose administration) of EIK1005 as monotherapy and in combination with pembrolizumab.
Time frame: Up to 1 year
Pharmacokinetic (PK) parameters of EIK1005 - t½ (Half-life) (Part 1 and Part 2)
Half-life (the time required for the plasma concentration of the drug to decrease by 50% after the dose administration) of EIK1005 as monotherapy and in combination with pembrolizumab.
Time frame: Up to 1 year
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