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Recruiting Phase 2

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

NCT07546812 · tracked via the Priya Life Science USA tracker
Phase
Phase 2
Started
2026-08-07
Last updated
2026-09-21

Condition(s) studied

HER2-negativeGastroesophageal JunctionEsophageal AdenocarcinomaGastric Adenocarcinoma

Investigational drug(s) / intervention(s)

Denikitug →Nivolumab →Ramucirumab →Paclitaxel →

Denikitug: Administered Intravenously

Nivolumab: Administered Intravenously

Ramucirumab: Administered Intravenously

Paclitaxel: Administered Intravenously

Study 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).

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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: 1. Platinum- and fluoropyrimidine-based chemotherapy. 2. 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). 3. 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.

Primary outcome measure(s)

  • Objective Response Rate (ORR) — 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.

Trial sites (15)

FacilityCityRegionStatus
Massachusetts General Hospital Boston Massachusetts Recruiting
Dana Farber Cancer Institute (DFCI) Boston Massachusetts Active Not Recruiting
New York Oncology Hematology Albany New York Recruiting
Weill Cornell Medicine - New York Presbyterian Hospital New York New York Recruiting
Chris O'Brien Lifehouse Camperdown New South Wales Recruiting
Royal North Shore Hospital St Leonards New South Wales Recruiting
Royal Brisbane and Women's Hospital Herston Queensland Recruiting
Flinders Medical Centre Bedford Park South Australia Recruiting
Hollywood Private Hospital Nedlands Western Australia Recruiting
Centre Leon Berard, department of medical oncology Lyon France Recruiting
Institut Paoli-Calmettes, department of medical oncology Marseille France Recruiting
Seoul National University Hospital Seoul South Korea Recruiting
Hospital Universitari Vall d'Hebron Barcelona Spain Recruiting
Hospital Universitario 12 de Octubre Madrid Spain Recruiting
Hospital Clinico Universitario de Valencia Valencia Spain Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07546812 on ClinicalTrials.gov ↗ ← All trials in the USA