This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of denikitug (also known as GS-1811) as monotherapy and in combination with zimberelimab in participants with advanced solid tumors. This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy, and Part F for both monotherapy and combination therapy) in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.
Part D allocation for 1 cohort will be randomized.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
304
Administered Intravenously
Administered Intravenously
University of California San Diego
La Jolla, California, United States
Stanford Cancer Center
Palo Alto, California, United States
Smilow Cancer Center
New Haven, Connecticut, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Sarah Cannon Research Institute at Mary Crowley
Dallas, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
NEXT Oncology
San Antonio, Texas, United States
University of Wisconsin Clinical Sciences Center
Madison, Wisconsin, United States
...and 15 more locations
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Part A and C
Time frame: Day 1 Through Day 21
Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time frame: First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0
Time frame: First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for Denikitug
Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
PK Parameter: Minimum Observed Concentration (Cmin) for Denikitug
Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
PK Parameter: Time of Maximum Observed Concentration (Tmax) for Denikitug
Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
PK Parameter: Area Under the Concentration-time Curve (AUC) for Denikitug
Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug
Time frame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
Objective response rate (ORR) in Part D
Objective response rate is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: Day 1 Up to End of Treatment (24 months)
Disease control rate (DCR)
Disease control rate is defined as the proportion of participants who achieve CR, PR, or stable disease (SD) as assessed by RECIST Version 1.1
Time frame: Day 1 Up to End of Treatment (24 months)
Time to response (TTR)
Time to response is defined as the time from the first dose of Denikitug in combination with Zimberelimab to the first documentation of CR or PR that is subsequently confirmed
Time frame: Day 1 Up to End of Treatment (24 months)
Duration of response (DOR)
Duration of response is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive progressive disease (PD) or death from any cause, if applicable.
Time frame: Day 1 Up to End of Treatment (24 months)
Progression-free survival (PFS)
Progression-free survival is defined as the time from the first dose of Denikitug in combination with Zimberelimab to the earlier of the first documentation of definitive PD or death from any cause
Time frame: Day 1 Up to End of Treatment (24 months)
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