Study of Denikitug (GS-1811) Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Zimberelimab; Drug: Denikitug

Detailed Description

Part D allocation for 1 cohort will be randomized.

• Study Type: Interventional
• Enrollment (Estimated): 416
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris O'Brien Lifehouse
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
• Canada
  • Toronto, Canada, M5G 2M9
    • Recruiting
    • University Health Network, Princess Margaret Cancer Centre
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d´Hebrón
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 De Octubre
  • Madrid, Spain, 28033
    • Recruiting
    • MD Anderson Cancer Center
  • Madrid, Spain, 28223
    • Recruiting
    • Hospital Universitario Quironsalud Madrid
  • Pamplona, Spain, 31008
    • Recruiting
    • Clínica Universidad de Navarra
• Taiwan
  • Changhua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital
  • Tainan, Taiwan, 73657
    • Recruiting
    • Chi Mei Hospital, Liouying
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 100229
    • Recruiting
    • National Taiwan University Cancer Center (NTUCC)
  • Taipei, Taiwan, 110
    • Withdrawn
    • Taipei Tzu Chi General Hospital
  • Taoyuan, Taiwan, 33308
    • Recruiting
    • Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital
• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California San Diego
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Completed
      • Smilow Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology, PLLC
  • Texas
    • Dallas, Texas, United States, 39090
      • Recruiting
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Sarah Cannon Research Institute at Mary Crowley
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin Clinical Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Disease:

  • Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
  • Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
  • Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or whose disease is indicated for anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-[L]1) monoclonal antibody monotherapy.
  • Part D: Individuals with pathologically confirmed select advanced solid tumors.
  • Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit.
  • Part F: Individuals with pathologically-confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatments known to confer clinical benefit; or, for participants who will undergo combination therapy, have disease which is indicated for anti-PD-(L)1 mAb monotherapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.

• Tissue requirement:

  • Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample prior to enrollment.
  • Part B and select participants in Parts C and F: Must have fresh pre-treatment and on-treatment biopsies for biomarker analysis.

Key Exclusion Criteria:

• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B - Mandatory Paired Tumor Biopsy	Drug: Denikitug; Administered Intravenously; Other Names: GS-1811
Experimental: Part A - Denikitug Dose Escalation	Drug: Denikitug; Administered Intravenously; Other Names: GS-1811
Experimental: Part C: Denikitug + Zimberelimab Dose Escalation	Drug: Zimberelimab; Administered Intravenously; Drug: Denikitug; Administered Intravenously; Other Names: GS-1811
Experimental: Part D: Denikitug + Zimberelimab Dose Expansion	Drug: Zimberelimab; Administered Intravenously; Drug: Denikitug; Administered Intravenously; Other Names: GS-1811
Experimental: Part E: Denikitug Monotherapy Dose Expansion	Drug: Denikitug; Administered Intravenously; Other Names: GS-1811
Experimental: Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule	Drug: Zimberelimab; Administered Intravenously; Drug: Denikitug; Administered Intravenously; Other Names: GS-1811

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	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	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 Dose Limiting Toxicities (DLTs) in Part A and C	Day 1 Through Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Day 1 Up to End of Treatment (24 months)
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	Day 1 Up to End of Treatment (24 months)
Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for Denikitug		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		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		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		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		Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
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	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	Day 1 Up to End of Treatment (24 months)

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; zimberelimab
• Other Study ID Numbers: GS-US-570-6015; 2022-501684-40 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No