This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants with advanced solid tumors. In addition, dostarlimab will be given as monotherapy (Arm D); and in combination with belrestotug (Arm E); and with GSK6097608 + belrestotug (Arm F) in Japanese and Chinese participants. The study may assess the PK/PD cohorts for Arm E and/or Arm F in participants outside of China and Japan. Additionally, dostarlimab will be given in combination with cobolimab in Japanese participants. Drug name mentioned as belrestotug, GSK4428859A and EOS884448 are interchangeable for the same compound. In the rest of the document, the drug will be referred to as belrestotug.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
107
GSK6097608 will be administered as an IV infusion.
Dostarlimab will be administered as an IV infusion.
Cobolimab will be administered as an IV infusion.
Belrestotug will be administered as an IV infusion.
GSK Investigational Site
Los Angeles, California, United States
GSK Investigational Site
Boston, Massachusetts, United States
GSK Investigational Site
Dallas, Texas, United States
GSK Investigational Site
Houston, Texas, United States
GSK Investigational Site
San Antonio, Texas, United States
GSK Investigational Site
Ottawa, Ontario, Canada
GSK Investigational Site
Toronto, Ontario, Canada
GSK Investigational Site
Chiba, Japan
GSK Investigational Site
Tokyo, Japan
GSK Investigational Site
Seoul, South Korea
...and 1 more locations
Number of participants with dose-limiting toxicities (DLTs)
Time frame: Up to Day 21
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time frame: Up to 2 years
Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings
Time frame: Up to 2 years
Number of participants with dose reductions or delay
Time frame: Up to 2 years
Number of participants withdrawn due to AEs
Time frame: Up to 2 years
Overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Up to 2 years
Arms D, E, F, G: ORR based on modified Response Evaluation Criteria in Solid Tumors (iRECIST)
Time frame: Up to 2 years
Arms D, E, F, G: Disease Control Rate (DCR) based on RECIST 1.1
Time frame: Up to 2 years
Arms D, E, F, G: DCR based on iRECIST
Time frame: Up to 2 years
Arms D, E, F, G: Time to response (TTR) based on RECIST 1.1
Time frame: Up to 2 years
Arms D, E, F, G: TTR based on iRECIST
Time frame: Up to 2 years
Arms D, E, F, G: Duration of response (DOR) based on RECIST 1.1
Time frame: Up to 2 years
Arms D, E, F, G: DOR based on iRECIST
Time frame: Up to 2 years
Arms D, E, F, G: Progression-free survival (PFS) based on RECIST 1.1
Time frame: Up to 2 years
Arms D, E, F, G: PFS based on iRECIST
Time frame: Up to 2 years
Arms A, B, F: Number of participants with positive anti-drug antibodies (ADAs) against GSK6097608
Time frame: Up to 2 years
Arms A, B, F: Titers of ADAs against GSK6097608
Time frame: Up to 2 years
Arms B, D, E, F, G: Number of participants with positive ADAs against dostarlimab
Time frame: Up to 2 years
Arms B, D, E, F, G: Titers of ADAs against dostarlimab
Time frame: Up to 2 years
Arms E, F: Number of participants with positive ADAs against belrestotug
Time frame: Up to 2 years
Arms E, F: Titers of ADAs against belrestotug
Time frame: Up to 2 years
Arm G: Number of participants with positive ADAs against cobolimab
Time frame: Up to 2 years
Arm G: Titers of ADAs against cobolimab
Time frame: Up to 2 years
Arms A, B, F: Maximum observed concentration (Cmax) for GSK6097608
Time frame: Up to 2 years
Arms A, B, F: Minimum observed concentration (Cmin) for GSK6097608
Time frame: Up to 2 years
Arms A, B, F: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-infinity]) for GSK6097608
Time frame: Up to 2 years
Arms A, B, F: Area under the plasma concentration-time curve from time zero to time (AUC[0-t]) for GSK6097608
Time frame: Up to 2 years
Arms A, B, F: Apparent terminal phase half-life (t1/2) for GSK6097608
Time frame: Up to 2 years
Arms B, D, E, F, G: Cmax for dostarlimab
Time frame: Up to 2 years
Arms B, D, E, F, G: Cmin for dostarlimab
Time frame: Up to 2 years
Arms B, D, E, F, G: AUC(0-infinity) for dostarlimab
Time frame: Up to 2 years
Arms B, D, E, F, G: AUC(0-t) for dostarlimab
Time frame: Up to 2 years
Arms B, D, E, F, G: t1/2 for dostarlimab
Time frame: Up to 2 years
Arms E, F: Cmax for belrestotug
Time frame: Up to 2 years
Arms E, F: Cmin for belrestotug
Time frame: Up to 2 years
Arms E, F: AUC(0-infinity) for belrestotug
Time frame: Up to 2 years
Arms E, F: AUC(0-t) for belrestotug
Time frame: Up to 2 years
Arms E, F: t1/2 for belrestotug
Time frame: Up to 2 years
Arm G: Cmax for cobolimab
Time frame: Up to 2 years
Arm G: Cmin for cobolimab
Time frame: Up to 2 years
Arm G: AUC(0-infinity) for cobolimab
Time frame: Up to 2 years
Arm G: AUC(0-t) for cobolimab
Time frame: Up to 2 years
Arm G: t1/2 for cobolimab
Time frame: Up to 2 years
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