A Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Denikitug (GS-1811), an Afucosylated Anti-CCR8 Monoclonal Antibody, as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors
Summary
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.
Detailed description
Part D allocation for 1 cohort will be randomized.
Arms & interventions
- DrugDenikitug
Administered Intravenously
- DrugZimberelimab
Administered Intravenously
Outcome measures
Primary
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
Secondary
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
Time frame: Day 1 Up to End of Treatment (24 months)
Disease control rate (DCR)
Time frame: Day 1 Up to End of Treatment (24 months)
Time to response (TTR)
Time frame: Day 1 Up to End of Treatment (24 months)
Duration of response (DOR)
Time frame: Day 1 Up to End of Treatment (24 months)
Progression-free survival (PFS)
Time frame: Day 1 Up to End of Treatment (24 months)
Eligibility criteria
Study locations (10)
University of California San Diego
La Jolla, California, 92093
Stanford Cancer Center
Palo Alto, California, 94305
Smilow Cancer Center
New Haven, Connecticut, 06510
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
University of Texas Southwestern Medical Center
Dallas, Texas, 39090
Sarah Cannon Research Institute at Mary Crowley
Dallas, Texas, 75230
MD Anderson Cancer Center
Houston, Texas, 77030
NEXT Oncology
San Antonio, Texas, 78229
University of Wisconsin Clinical Sciences Center
Madison, Wisconsin, 53705