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

A Phase 2, Open Label, Multicenter, Randomized Study, to Evaluate the Efficacy and Safety of Denikitug Monotherapy and Denikitug-based Combinations in Participants With Advanced Microsatellite Stable (MSS) Colorectal Cancer (CRC)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Microsatellite Stable Colorectal Cancer
• Intervention / Treatment: Drug: Denikitug; Drug: Nivolumab; Drug: Bevacizumab; Drug: Trifluridine-Tipiracil

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 2

Contacts and Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEN monotherapy (Arm A); Participants will receive DEN via intravenous (IV) infusion.	Drug: Denikitug; Administered Intravenously; Other Names: GS-1811; DEN
Experimental: DEN in combination with NIVO (Arm B); Participants will receive DEN as an IV infusion in combination with NIVO as an IV infusion.	Drug: Denikitug; Administered Intravenously; Other Names: GS-1811; DEN; Drug: Nivolumab; Administered Intravenously; Other Names: NIVO
Experimental: DEN in combination with Trifluridine-Tipiracil (FTD-TPI) and BVZ (Arm C); Participants will receive DEN as an IV infusion in combination with BVZ as an IV infusion and FTD-TPI administered orally. Includes a Safety Run-in cohort (non-randomized cohort) prior to randomization.	Drug: Denikitug; Administered Intravenously; Other Names: GS-1811; DEN; Drug: Bevacizumab; Administered Intravenously; Other Names: BVZ; Drug: Trifluridine-Tipiracil; Administered orally; Other Names: FTD-TPI
Active Comparator: Standard of care (SOC) alone: BVZ and FTD-TPI (Arm D); Participants will receive BVZ as an IV infusion and FTD-TPI administered orally as SOC.	Drug: Bevacizumab; Administered Intravenously; Other Names: BVZ; Drug: Trifluridine-Tipiracil; Administered orally; Other Names: FTD-TPI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST Version 1.1.	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	DOR is defined as the time from first response (CR or PR) as assessed by investigator, per RECIST Version 1.1 until the date of first documented progressive disease (PD) or death, whichever comes first.	Up to 60 months
Progression-Free Survival (PFS)	PFS is defined as the time from date of randomization until PD or death from any cause, whichever comes first as assessed by the investigator according to RECIST Version 1.1.	Up to 60 months
Overall Survival (OS)	OS is defined as the length of time from randomization until the date of death from any cause.	Up to 60 months
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 date up to 120 days post last dose, up to 60 months
Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0		First dose date up to 120 days post last dose, up to 60 months
Pharmacokinetic (PK) Parameter: Serum concentration of Denikitug		Up to 36 months
PK Parameter: Cmax for Denikitug	Cmax is defined as the maximum observed concentration.	Up to 36 months
PK Parameter: AUCall for Denikitug	AUCall is defined as the cumulative areas under the curve for all time points.	Up to 36 months
Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug		Up to 36 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Bevacizumab; trifluridine tipiracil drug combination
• Other Study ID Numbers: GS-US-741-7756; 2025-523984-39 (Other Identifier: EU Trial (CTIS))

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