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

NCT07546812 | Recruiting Phase 2 FDA Drug

• 4 other identifiers: GS-US-742-77572025-524095-27CTR202632042025
• Study Type: interventional
• Target: 120
• Locations: 5 countries
• Sites: 15

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 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).

Conditions

HER2-negative; Gastroesophageal Junction; Esophageal Adenocarcinoma; Gastric Adenocarcinoma

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 4 years

Secondary Outcomes (9)

• Duration of Response (DOR)

  Up to 4 years

• Progression-Free Survival (PFS)

  Up to 4 years

• Overall Survival (OS)

  Up to 4 years

• 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

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

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

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

Study Arms (5)

Part 1: Arm A: DEN (Dose A) and NIVO

EXPERIMENTAL

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

Drug: Denikitug; Drug: Nivolumab

Part 1: Arm B: DEN (Dose B) and NIVO

EXPERIMENTAL

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

Drug: Denikitug; Drug: Nivolumab

Part 1: Arm C: DEN (Dose B)

EXPERIMENTAL

Participants will receive DEN Dose B as an IV infusion.

Drug: Denikitug

Part 2: Arm D: Safety Run-in (SRI) Cohort

EXPERIMENTAL

Participants will receive DEN in combination with ramucirumab (RAM) and paclitaxel (PAC). If dose for DEN is deemed safe during the SRI Cohort, the study will move forward into the Expansion Period.

Drug: Denikitug; Drug: Ramucirumab; Drug: Paclitaxel

Part 2: Arm D: Expansion Cohort

EXPERIMENTAL

If DEN dose is deemed safe in Arm D: SRI Cohort, participants will receive DEN at recommended dose as an IV infusion in combination with RAM and PAC.

Drug: Denikitug; Drug: Ramucirumab; Drug: Paclitaxel

Interventions

Denikitug DRUG

Administered Intravenously

Also known as: GS-1811

Part 1: Arm A: DEN (Dose A) and NIVO; Part 1: Arm B: DEN (Dose B) and NIVO; Part 1: Arm C: DEN (Dose B); Part 2: Arm D: Expansion Cohort; Part 2: Arm D: Safety Run-in (SRI) Cohort

Nivolumab DRUG

Administered Intravenously

Part 1: Arm A: DEN (Dose A) and NIVO; Part 1: Arm B: DEN (Dose B) and NIVO

Ramucirumab DRUG

Administered Intravenously

Part 2: Arm D: Expansion Cohort; Part 2: Arm D: Safety Run-in (SRI) Cohort

Paclitaxel DRUG

Administered Intravenously

Part 2: Arm D: Expansion Cohort; Part 2: Arm D: Safety Run-in (SRI) Cohort

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (15)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02215, United States

ACTIVE NOT RECRUITING

New York Oncology Hematology

Albany, New York, 12206, United States

RECRUITING

Weill Cornell Medicine - New York Presbyterian Hospital

New York, New York, 10021, United States

RECRUITING

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

RECRUITING

Hollywood Private Hospital

Nedlands, Western Australia, 6009, Australia

RECRUITING

Centre Leon Berard, department of medical oncology

Lyon, 69008, France

RECRUITING

Institut Paoli-Calmettes, department of medical oncology

Marseille, 13009, France

RECRUITING

Seoul National University Hospital

Seoul, 03830, South Korea

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

Nivolumab; Ramucirumab; Paclitaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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

Model Details: Arms in Part 1 received treatment in parallel. Part 1 and Part 2 were sequential assignment.

Study Record Dates

• First Submitted: April 17, 2026
• First Posted: April 23, 2026
• Study Start: August 7, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); AU (5); ES (3); FR (2); KR (1)