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

NCT05007782 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: GS-US-570-60152022-501684-40
• Study Type: interventional
• Target: 416
• Locations: 5 countries
• Sites: 26

Brief 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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Part A and C

  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

  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

Secondary Outcomes (10)

• 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

Study Arms (6)

Part A - Denikitug Dose Escalation

EXPERIMENTAL

Drug: Denikitug

Part B - Mandatory Paired Tumor Biopsy

EXPERIMENTAL

Drug: Denikitug

Part C: Denikitug + Zimberelimab Dose Escalation

EXPERIMENTAL

Drug: Denikitug; Drug: Zimberelimab

Part D: Denikitug + Zimberelimab Dose Expansion

EXPERIMENTAL

Drug: Denikitug; Drug: Zimberelimab

Part E: Denikitug Monotherapy Dose Expansion

EXPERIMENTAL

Drug: Denikitug

Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule

EXPERIMENTAL

Drug: Denikitug; Drug: Zimberelimab

Interventions

Denikitug DRUG

Administered Intravenously

Also known as: GS-1811

Part A - Denikitug Dose Escalation; Part B - Mandatory Paired Tumor Biopsy; Part C: Denikitug + Zimberelimab Dose Escalation; Part D: Denikitug + Zimberelimab Dose Expansion; Part E: Denikitug Monotherapy Dose Expansion; Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule

Zimberelimab DRUG

Administered Intravenously

Part C: Denikitug + Zimberelimab Dose Escalation; Part D: Denikitug + Zimberelimab Dose Expansion; Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (26)

University of California San Diego

La Jolla, California, 92093, United States

RECRUITING

Stanford Cancer Center

Palo Alto, California, 94305, United States

RECRUITING

Smilow Cancer Center

New Haven, Connecticut, 06510, United States

COMPLETED

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 39090, United States

RECRUITING

Sarah Cannon Research Institute at Mary Crowley

Dallas, Texas, 75230, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

University of Wisconsin Clinical Sciences Center

Madison, Wisconsin, 53705, United States

RECRUITING

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

Monash Medical Centre

Clayton, Victoria, 3168, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

University Health Network, Princess Margaret Cancer Centre

Toronto, M5G 2M9, Canada

RECRUITING

Hospital Universitari Vall d´Hebrón

Barcelona, 08035, Spain

RECRUITING

MD Anderson Cancer Center

Madrid, 28033, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Quironsalud Madrid

Madrid, 28223, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, 31008, Spain

RECRUITING

Changhua Christian Hospital

Changhua, 500, Taiwan

RECRUITING

Chi Mei Hospital, Liouying

Tainan, 73657, Taiwan

RECRUITING

National Taiwan University Cancer Center (NTUCC)

Taipei, 100229, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Taipei Tzu Chi General Hospital

Taipei, 110, Taiwan

WITHDRAWN

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital

Taoyuan, 33308, Taiwan

RECRUITING

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

zimberelimab

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Central Study Contacts

Gilead Clinical Study Information Center

CONTACT

1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 16, 2021
• Study Start: August 18, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); US (10); CA (1); TW (7); ES (5)