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NCT Number: NCT07546812

Study of Denikitug (GS-1811) Given Alone or With Nivolumab or Chemotherapy in Adults With Metastatic Gastric, Gastroesophageal Junction (GEJ), and Esophageal Adenocarcinomas

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 in participants with human epidermal growth factor receptor 2 (HER2)-Negative, unresectable, recurrent, and/or metastatic, gastroesophageal junction (GEJ), and esophageal adenocarcinomas.

The primary objective of this study is to assess the effect of DEN as a monotherapy or in combination with nivolumab (NIVO) or ramucirumab (RAM) and paclitaxel (PAC) on objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST Version1.1).

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of locally advanced, unresectable, or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma (EAC).
  • Human epidermal growth factor receptor 2 (HER2)-negative status, as determined by local assessment using a validated immunohistochemistry assay, in situ hybridization or other amplification testing.
  • Has had disease progression during or after first line of systemic therapy for advanced or metastatic gastric, GEJ, or EACs, which must have included at least one of the following:
  • Platinum- and fluoropyrimidine-based chemotherapy.
  • Therapy with an anti-programmed cell death protein 1 (PD1) or anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody (patients with PD-L1-positive tumors must have received prior PD-1/PD-L1-based therapy).
  • Zolbetuximab or other Claudin-18 (CLDN18).2-targeted therapy, if indicated based on biomarker status.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
  • Have adequate organ function.
  • Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.

Key Exclusion Criteria:

  • Active or history of autoimmune disease requiring systemic treatment within 2 years, inflammatory bowel disease (IBD) (Crohn's/ulcerative colitis), celiac disease, or noninfectious enteritis/colitis. (Physiologic hormone replacement not considered systemic treatment).
  • History or current noninfectious pneumonitis/interstitial lung disease, including radiation-induced pneumonitis requiring steroids or active/recurrent pneumonitis of any etiology.
  • Documented microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) disease by local polymerase chain reaction (PCR) (microsatellite status) and/or informed consent form (ICH) (mismatch repair (MMR)) assay
  • (For Part 2 only) Has known history of peripheral neuropathy ≥ Grade 2 (per National Cancer Institute(NCI)-Common Tenninology Criteria for Adverse Events (CTCAE) Version 5.0).
  • (For Part 2 only) Known coagulopathy that increases the risk of bleeding, bleeding diatheses. Any other Grade 3 or higher hemorrhage/bleeding event within 28 days prior to enrollment.

Prior/Concurrent Therapy or Clinical Study Experience

  • Prior treatment with DEN or other C-C chemokine receptor 8 (CCR8)-targeted agents.
  • Prior Lonsurf (trifluridine-tipiracil) or paclitaxel (PAC)-based regimens in the first-line setting for advanced/metastatic gastroesophageal adenocarcinoma.
  • Any systemic therapy (including investigational) targeting vascular endothelial growth factor (VEGF) or VEGF receptor (VEGFR) signaling pathways.
  • Anticancer biologic within 4 weeks, orchemotherapy, targeted small molecule, or radiation therapy within 2 weeks prior to enrollment with unresolved adverse events (AE)s (Grade >2). (Observational study participants are eligible).
  • Prior allogenic tissue/solid organ or stem cell transplantation. (Exception: corneal transplant not requiring systemic immunosuppression is allowed).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

Denikitug

Drug

Administered Intravenously

Other names: GS-1811

Nivolumab

Drug

Administered Intravenously

Ramucirumab

Drug

Administered Intravenously

paclitaxel

Drug

Administered Intravenously

Primary outcomes

  1. Objective Response Rate (ORR)

    Time frame: Up to 4 years

    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.

Secondary outcomes

  1. Duration of Response (DOR)

    Time frame: Up to 4 years

    DOR is defined as the time of 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.

  2. Progression-Free Survival (PFS)

    Time frame: Up to 4 years

    PFS is defined as the time from date of first dose until PD or death from any cause, whichever comes first as assessed by the investigator according to RECIST Version 1.1.

  3. Overall Survival (OS)

    Time frame: Up to 4 years

    OS is defined as the length of time from first dose until the date of death from any cause.

  4. Percentage of Participants Experiencing Treatment-Emergent Adverse Event (TEAEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

    Time frame: First dose date up to 120 days post last dose, up to 4 years.

  5. Percentage of Participants Experiencing Clinical Laboratory Abnormalities According to the NCI CTCAE v5.0

    Time frame: First dose date up to 120 days post last dose, up to 4 years.

  6. Pharmacokinetic (PK) Parameter: Serum concentration of DEN

    Time frame: Up to 4 years

  7. PK Parameter: Cmax for Denikitug

    Time frame: Up to 4 years

    Cmax is defined as the maximum observed concentration.

  8. PK Parameter: AUCall for Denikitug

    Time frame: Up to 4 years

    AUCall is defined as the cumulative areas under the curve for all time points.

  9. Percentage of Participants who Developed Treatment-Emergent Antidrug Antibody (ADA) Against Denikitug

    Time frame: Up to 4 years

Study contacts

Contact information is provided by the study sponsor or research team.

Gilead Clinical Study Information Center

CONTACT

[email protected]

1-833-445-3230 (GILEAD-0)

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study title

A Phase 2, Open-Label, Multicenter, Randomized Study to Evaluate Denikitug as Monotherapy or in Combination With Nivolumab or Chemotherapy in Participants With HER2-Negative, Unresectable, Recurrent, and/or Metastatic Gastric, Gastroesophageal Junction (GEJ), and Esophageal Adenocarcinomas

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Apr 23, 2026
Registry last updated
Jul 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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