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NCT07527858PHASE2Recruiting

Study of Denikitug (GS-1811) Given Alone or With Nivolumab or With Chemotherapy in Adults With Advanced Colorectal Cancer

Gilead Sciences

Start Date

5/19/2026

Completion Date

12/1/2028

Summary

The goal of this clinical study is to learn more about the study drug, Denikitug (DEN, GS-1811), to evaluate the efficacy and safety of Denikitug Monotherapy and Denikitug-based Combinations in participants with advanced microsatellite stable (MSS) colorectal cancer (CRC). The primary objective of this study is to assess the effect of DEN as monotherapy and in combination with nivolumab (NIVO) or trifluridine-tipiracil (FTD-TPI) and bevacizumab (BVZ) on objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1).

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: Medical History/Physical Characteristics * Histologically or cytologically confirmed unresectable, recurrent, or locally advanced or metastatic microsatellite stable colorectal cancer (MSS CRC) (adenocarcinoma, excluding appendix cancer). * Documented MSS or proficient mismatch repair (pMMR) disease by local assessment using a validated polymerase chain reaction (PCR) (microsatellite status) and/or immunohistochemistry (IHC) mismatch repair (MMR) assay is required. * Has received up to 2 prior lines of systemic therapy for advanced or metastatic CRC, which must have included at least fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapies if indicated; and if applicable: anti-vascular endothelial growth factor (VEGF) therapy, anti epidermal growth factor receptor (EGFR) therapy, encorafenib or adagrasib/sotorasib. * Documented progressive disease (PD) by computed tomography (CT) or magnetic resonance imaging (MRI) during or after the most recent therapy per RECIST Version 1.1 criteria by investigator assessment. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. Laboratory Assessments * Have adequate organ function. Key Exclusion Criteria with: Medical Conditions/History: * Significant cardiovascular disease. * History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years. * History of (noninfectious) pneumonitis/interstitial lung disease or current pneumonitis/ interstitial lung disease. * History of gastrointestinal (GI) perforation, permanent ileostomy, abdominal abscess or fistula within 6 months, active or uncontrolled GI bleeding within 4 weeks, or any condition associated with significant risk of bleeding or perforation (eg, untreated varices, tumor erosion, recent GI surgery). Prior/Concurrent Therapy or Clinical Study Experience Prior treatment with: * Trifluridine-tipiracil, regorafenib, or fruquitinib. * Any immuno-oncology therapy. * Anticancer biologic agent within 4 weeks prior to randomization or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to randomization and have not recovered (ie, Grade 2 or less) from AEs from prior anticancer therapy at the time of randomization. Individuals in observational studies are eligible. * Allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Interventions

DRUG

Denikitug

DRUG

Nivolumab

DRUG

Bevacizumab

DRUG

Trifluridine-Tipiracil

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Conditions

Advanced Microsatellite Stable Colorectal Cancer

Locations

Yale-New Haven Hospital - Yale Cancer Center

North Haven, Connecticut 06473 2195

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts 02215

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Avera Cancer Institute

Sioux Falls, South Dakota 57105

United States

University of Virginia,

Charlottesville, Virginia 22908

United States

Chris O'Brien Lifehouse

Camperdown, CA 2050

Australia

Royal Brisbane and Women's Hospital

Herston, Queensland 4029

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Samsung Medical Center

Busan, 48775

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Yonsei University Severance Hospital ( aka Yonsei Cancer Center)

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 138-736

South Korea

Hospital General Universitario Gregorio Maranon

Madrid, 28050

Spain