Recruiting
Phase 2

Denikitug, Nivolumab, FTD-TPI, BVZ

Sponsor:

Gilead Sciences

Code:

NCT07527858

Conditions

Advanced Microsatellite Stable Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Denikitug

Nivolumab

Bevacizumab

Trifluridine-Tipiracil

Study Details

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

Study ID

NCT07527858

Start date

May 19, 2026

Status verified date

Jul, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

170 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: DEN monotherapy (Arm A)

Participants will receive DEN via intravenous (IV) infusion.

experimental: DEN in combination with NIVO (Arm B)

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

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.

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.

Interventions

Denikitug

Administered Intravenously

Nivolumab

Administered Intravenously

Bevacizumab

Administered Intravenously

Trifluridine-Tipiracil

Administered orally

Primary outcome measure

  • Objective Response Rate (ORR) [ Time Frame: Up to 60 months ]

Central Contacts and Locations

Central contacts

Gilead Clinical Study Information Center

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

Locations

Yale-New Haven Hospital - Yale Cancer Center

Recruiting

North Haven, Connecticut, United States, 06473 2195

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02215

Avera Cancer Institute

Recruiting

Sioux Falls, South Dakota, United States, 57105

University of Virginia,

Recruiting

Charlottesville, Virginia, United States, 22908

More Information

Sponsor

Gilead Sciences

Last update posted

Jul 28, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Gilead Sciences on 2026-07-28.