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

NCT07527858 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: GS-US-741-77562025-523984-39
• Study Type: interventional
• Target: 170
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

Advanced Microsatellite Stable Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Duration of response (DOR)

  Up to 60 months

• Progression-Free Survival (PFS)

  Up to 60 months

• Overall Survival (OS)

  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

Study Arms (4)

DEN monotherapy (Arm A)

EXPERIMENTAL

Participants will receive DEN via intravenous (IV) infusion.

Drug: Denikitug

DEN in combination with NIVO (Arm B)

EXPERIMENTAL

Participants will receive DEN as an IV infusion in combination with NIVO as an IV infusion.

Drug: Denikitug; Drug: Nivolumab

DEN in combination with Trifluridine-Tipiracil (FTD-TPI) and BVZ (Arm C)

EXPERIMENTAL

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; Drug: Bevacizumab; Drug: Trifluridine-Tipiracil

Standard of care (SOC) alone: BVZ and FTD-TPI (Arm D)

ACTIVE COMPARATOR

Participants will receive BVZ as an IV infusion and FTD-TPI administered orally as SOC.

Drug: Bevacizumab; Drug: Trifluridine-Tipiracil

Interventions

Denikitug DRUG

Administered Intravenously

Also known as: GS-1811, DEN

DEN in combination with NIVO (Arm B); DEN in combination with Trifluridine-Tipiracil (FTD-TPI) and BVZ (Arm C); DEN monotherapy (Arm A)

Nivolumab DRUG

Administered Intravenously

Also known as: NIVO

DEN in combination with NIVO (Arm B)

Trifluridine-Tipiracil DRUG

Administered orally

Also known as: FTD-TPI

DEN in combination with Trifluridine-Tipiracil (FTD-TPI) and BVZ (Arm C); Standard of care (SOC) alone: BVZ and FTD-TPI (Arm D)

Bevacizumab DRUG

Administered Intravenously

Also known as: BVZ

DEN in combination with Trifluridine-Tipiracil (FTD-TPI) and BVZ (Arm C); Standard of care (SOC) alone: BVZ and FTD-TPI (Arm D)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

MeSH Terms

Interventions

Nivolumab; Bevacizumab; trifluridine tipiracil drug combination

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share