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NCT05007782PHASE1Recruiting

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

Gilead Sciences

Start Date

8/18/2021

Completion Date

12/1/2028

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Denikitug

DRUG

Zimberelimab

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Conditions

Advanced Solid Tumor

Locations

University of California San Diego

La Jolla, California 92093

United States

Stanford Cancer Center

Palo Alto, California 94305

United States

Smilow Cancer Center

New Haven, Connecticut 06510

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts 02215

United States

Tennessee Oncology, PLLC

Nashville, Tennessee 37203

United States

University of Texas Southwestern Medical Center

Dallas, Texas 39090

United States

Sarah Cannon Research Institute at Mary Crowley

Dallas, Texas 75230

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

NEXT Oncology

San Antonio, Texas 78229

United States

University of Wisconsin Clinical Sciences Center

Madison, Wisconsin 53705

United States

Chris O'Brien Lifehouse

Camperdown, New South Wales 2050

Australia

Monash Medical Centre

Clayton, Victoria 3168

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

University Health Network, Princess Margaret Cancer Centre

Toronto, M5G 2M9

Canada

Hospital Universitari Vall d´Hebrón

Barcelona, 08035

Spain

MD Anderson Cancer Center

Madrid, 28033

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario Quironsalud Madrid

Madrid, 28223

Spain

Clinica Universidad de Navarra

Pamplona, 31008

Spain

Changhua Christian Hospital

Changhua, 500

Taiwan

Chi Mei Hospital, Liouying

Tainan, 73657

Taiwan

National Taiwan University Cancer Center (NTUCC)

Taipei, 100229

Taiwan

National Taiwan University Hospital

Taipei, 100

Taiwan

Taipei Tzu Chi General Hospital

Taipei, 110

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital

Taoyuan City, 33308

Taiwan