Study of denikitug alone or with drug combination in adults with HER2‑negative metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma

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What is this study about?

The study focuses on adults with advanced HER2-negative gastric, gastroesophageal junction, and esophageal adenocarcinomas that cannot be removed by surgery and have returned or spread to other parts of the body. The investigational drug is denikitug (code name DEN), a laboratory‑made monoclonal antibody given by intravenous infusion. Participants may receive DEN alone or combined with the immune‑stimulating drug nivolumab or with a chemotherapy regimen that includes the blood‑vessel targeting agent ramucirumab together with the cancer‑killing drug paclitaxel.

The purpose of the study is to evaluate how these treatment approaches affect tumor shrinkage, measured as the objective response rate, which is the percentage of patients whose scans show a significant reduction in tumor size. Tumor changes are assessed using a set of rules called RECIST, which helps doctors determine whether a tumor has partially or completely responded. Participants are randomly assigned to one of the treatment options and receive the infusions at regular intervals while undergoing periodic doctor visits, scans, and blood tests to monitor their condition.

Treatment continues until the disease gets worse, side effects become unacceptable, or the study ends. Throughout the study, any side effects are recorded and graded using a standard system known as CTCAE, ensuring that safety is closely watched alongside the effectiveness of the therapy.

1 study enrollment

after signing the consent form, you are officially entered into the study.

2 baseline assessments

a complete medical history, physical examination, blood tests, and imaging scans are performed to document the condition of your disease before any treatment.

the results are used to determine eligibility and to serve as reference points for later comparisons.

3 randomization to treatment group

based on the study design, you are assigned to one of three possible groups:

denikitug alone,

denikitug together with nivolumab,

or denikitug together with ramucirumab and paclitaxel.

4 first infusion visit

on the scheduled day, you receive the assigned medication(s) by intravenous infusion in a clinical setting.

the infusion is performed by trained staff and may last from several minutes to a few hours, depending on the drug.

5 subsequent infusion visits

you return for additional infusion appointments according to the study schedule.

each visit includes the same intravenous infusion of the assigned medication(s).

the exact frequency and duration of treatment are defined by the study protocol.

6 clinical monitoring

at each visit, vital signs, blood work, and any side effects are recorded.

the study team evaluates the safety of the treatment and may adjust care as needed.

7 tumor response assessments

periodic imaging scans are performed to measure changes in tumor size.

the primary outcome is the objective response rate, which indicates whether the tumor has shrunk (partial response) or disappeared (complete response) according to standard criteria.

8 continuation or end of treatment

treatment continues until the protocol‑specified number of cycles is completed, disease progression is observed, or unacceptable side effects occur.

if treatment stops, you enter a follow‑up phase with regular assessments to monitor disease status and overall health.

9 study follow‑up

after the last infusion, you remain in the study for scheduled follow‑up visits.

these visits track long‑term outcomes such as time until disease progression, overall survival, and any late side effects.

Who Can Join the Study?

Be assigned male or female at birth, be 18 years of age or older, understand the study, and be able to sign a written consent form and follow the treatment plan.
Have adequate organ function as shown by the required blood and other laboratory tests (extra lab requirements apply to a later part of the study).
Expect to live at least 3 more months.
Be willing and able to follow all study procedures and sign the consent before any testing begins.
Provide a sample of tumor tissue that was taken previously (ideally within the last 12 months) or a fresh biopsy, in a special preserved form called a formalin‑fixed paraffin‑embedded block or at least 15 thin, unstained slides; if fewer slides are available, the study team may still consider participation.
If you are of childbearing potential and have heterosexual intercourse, you must agree to use the study‑specified contraception methods.
Have a confirmed diagnosis (by microscope review of tissue) of locally advanced, unresectable, or metastatic gastric, gastro‑esophageal junction (GEJ), or esophageal adenocarcinoma.
Have a HER2‑negative tumor, meaning tests such as immunohistochemistry or in‑situ hybridization did not show excess HER2 protein or gene copies.
Have disease that got worse (progressed) during or after the first line of systemic therapy for advanced disease, which must have included at least one of the following: chemotherapy with platinum‑ and fluoropyrimidine‑based drugs, therapy with an anti‑PD‑1 or anti‑PD‑L1 antibody (if the tumor was PD‑L1‑positive), or a drug that targets CLDN18.2 (such as zolbetuximab) when appropriate.
Have documented progressive disease (PD) as seen on a CT (computed tomography) or MRI (magnetic resonance imaging) scan after the most recent treatment, using the criteria called RECIST Version 1.1.
Have measurable cancer lesions on a CT or MRI scan according to RECIST Version 1.1 (tumors in areas that were previously treated with radiation can count if they have shown growth).
Have an ECOG performance status score of 0‑1, meaning you are fully active or able to carry out light work.
Show a negative serum pregnancy test at screening and at enrollment (for women who could become pregnant).

Who Cannot Join the Study?

Planning to breastfeed during the study or for 4 months after the last dose.
Having a type of esophageal cancer called squamous cell carcinoma or any other cancer that is not an adenocarcinoma (for example, small‑cell, neuroendocrine, lymphoma, gastrointestinal stromal tumor, or carcinoid).
Having a tumor that tests positive for MSI‑H (high microsatellite instability) or dMMR (deficient mismatch repair), which are special genetic features of some cancers.
Previously stopping immunotherapy because of severe side effects, or having had severe (grade 3 or higher) diarrhea or inflammation of the colon (colitis) caused by immunotherapy.
Having a serious wound, ulcer, or bone fracture that has not healed within the past 28 days.
Having uncontrolled high blood pressure (≥150 mm Hg systolic or ≥90 mm Hg diastolic) despite taking medicines.
Having nerve damage (peripheral neuropathy) that is grade 2 or higher (moderate to severe tingling, numbness, or weakness).
Having a deep‑vein blood clot (deep venous thromboembolic event) within the past 28 days.
Having a bleeding disorder that raises the risk of bleeding, or having a serious (grade 3 or higher) bleeding event within the past 28 days.
Using any medication that the study lists as prohibited.
Using other experimental (investigational) drugs within 4 weeks before enrollment.
Having a known allergy (hypersensitivity) to the study drug, its breakdown products, or any of its ingredients.
Previously receiving denikitug (DEN) or other drugs that target CCR8, or having received Lonsurf (trifluridine‑tipiracil) or paclitaxel as first‑line treatment for advanced stomach or esophageal cancer.
Previously receiving any therapy that blocks the VEGF (vascular endothelial growth factor) pathway, or an anticancer biologic drug within 4 weeks, or chemotherapy, targeted therapy, or radiation within 2 weeks without fully recovering (side effects must be grade 2 or less).
Having had an organ transplant (including stem‑cell transplant) from another person, except a cornea transplant that did not require ongoing immune‑suppressing medicines.
Having an immune‑deficiency disorder or taking strong systemic steroids (more than 10 mg of prednisone‑equivalent per day) or other immune‑suppressing medicines within 7 days before enrollment (topical, inhaled, or eye steroids are allowed).
Not having recovered from side effects of prior cancer treatment (must be grade 2 or less), except mild nerve problems or hair loss, and must have healed adequately from any major surgery.
Having previously received other anti‑angiogenic drugs (medicines that stop new blood‑vessel growth) (Part 2 only).
Taking therapeutic blood‑thinning medicines such as warfarin, low‑molecular‑weight heparin, or similar agents (low‑dose preventive anticoagulation is allowed).
Taking chronic non‑steroidal anti‑inflammatory drugs (NSAIDs) like ibuprofen, naproxen, or other anti‑platelet medicines such as clopidogrel (low‑dose aspirin up to 325 mg/day is permitted).
Having HIV infection with an uncontrolled viral load or taking medicines that could interfere with the study drugs.
Having active hepatitis B or hepatitis C infection, or a detectable viral load for either disease (positive blood tests for HBV surface antigen, HBV core antibody, or HCV antibody require confirmatory viral‑load testing).
Having other medical or psychiatric conditions that the doctor believes could interfere with the study, make it unsafe, or prevent completion of study visits.
Receiving a live attenuated vaccine (a weakened‑virus vaccine) within 4 weeks before enrollment.
Having another active cancer (second malignancy). A past cancer is allowed only if it was completely treated, there is no evidence of disease for at least 3 years, and it was a low‑risk type such as non‑melanoma skin cancer.
Having cancer that has spread to the brain or spinal‑meninges (central nervous system metastases or carcinomatous meningitis). Treated brain metastases are allowed only if they have been stable for at least 4 weeks, symptoms are back to baseline, no new lesions are seen, and steroid use is ≤10 mg prednisone‑equivalent per day.
Having certain serious heart or blood‑vessel problems, such as recent stroke, heart attack, unstable chest pain, serious irregular heart rhythm, heart failure that is moderate or worse (NYHA class II or higher), or a left‑ventricular ejection fraction below 40 %.
Having an active serious infection that currently requires antibiotics (preventive antibiotics are allowed).
Having an autoimmune disease (e.g., rheumatoid arthritis, lupus, Crohn’s disease, ulcerative colitis, celiac disease) that needed systemic treatment (like disease‑modifying drugs, steroids, or other immune‑suppressing medicines) within the past 2 years.
Having a history of non‑infectious lung inflammation (pneumonitis or interstitial lung disease), including radiation‑induced lung inflammation that required steroids, or having current lung inflammation of any cause.
Having had a gastrointestinal perforation, permanent ileostomy, abdominal abscess or fistula within the past 6 months, active uncontrolled GI bleeding within the past 4 weeks, or any condition that greatly increases the risk of bleeding or perforation (such as untreated varices, tumor erosion, or recent GI surgery).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Lille	Lille	France
Institut Gustave Roussy	Villejuif	France
Oncopole Claudius Regaud	Toulouse	France
Hospital Universitario Hm Sanchinarro	Madrid	Spain
Hospital Universitario De Navarra	Pamplona	Spain

Other Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Poitiers	Poitiers	France
Hopital Beaujon	Clichy	France
Hospital Universitario 12 De Octubre	Madrid	Spain
Ifxikccm Pqrkzpvtenszroz Cyqvzz Cwhtld	Marseille	France
Hblqyosw Vutg dlupghnl	Barcelona	Spain
Crrlzn Lyrl Brfyip	Lyon	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	06.04.2026
Spain	Not yet recruiting	06.04.2026

Trial locations

Investigated drugs:

GS-1811 (Denikitug) is a human‑engineered antibody designed to target a protein called CCR8 on certain immune cells. By binding to CCR8, the drug aims to modify the immune system’s response to cancer, helping the body recognize and attack tumor cells. In this study, it is being tested alone and together with other cancer medicines to see if it can improve treatment outcomes for advanced stomach‑type cancers.

Opdivo contains the active ingredient nivolumab, which is a type of immunotherapy known as a PD‑1 checkpoint inhibitor. It works by releasing the brakes on the immune system, allowing T‑cells to more effectively find and destroy cancer cells. In this trial, Opdivo is used either by itself as a comparison treatment or in combination with GS‑1811 to explore whether the two drugs together provide a stronger anti‑cancer effect.

Cyramza is the brand name for ramucirumab, a medication that blocks a receptor called VEGFR‑2, which tumors use to grow new blood vessels. By stopping this signal, Cyramza can slow or shrink tumor growth. In the study, it is given together with chemotherapy to see if adding GS‑1811 to this regimen improves the response in patients with advanced gastric‑type cancers.

Abraxane contains paclitaxel albumin‑bound, a chemotherapy drug that interferes with cancer cell division, causing the cells to die. The albumin‑bound form helps the drug get into tumors more efficiently. In this trial, Abraxane is combined with Cyramza as a standard chemotherapy regimen, and researchers are testing whether adding GS‑1811 to this combination can increase the chance of tumor shrinkage.

Investigated diseases:

Oesophageal adenocarcinoma

Gastric adenocarcinoma – This is a cancer that starts in the gland‑like cells lining the stomach. When it is HER2‑negative, it does not have a certain protein that can be targeted by some drugs. Tumors that cannot be removed by surgery are called unresectable. The disease may return after initial treatment, which is described as recurrent. It can also spread to other parts of the body, a stage known as metastatic.

Gastroesophageal junction adenocarcinoma – This cancer arises where the stomach meets the esophagus, in the glandular tissue of that area. Being HER2‑negative means the tumor lacks a specific growth‑promoting protein. If the tumor cannot be surgically removed, it is termed unresectable. It may appear again after earlier therapy, described as recurrent. The cancer can extend beyond the junction to distant sites, which is called metastatic.

Esophageal adenocarcinoma – This disease develops from glandular cells in the lower part of the esophagus. HER2‑negative status indicates the absence of a particular cell‑surface receptor. Tumors that cannot be taken out by surgery are classified as unresectable. They may come back after treatment, known as recurrent disease. The cancer can also spread to other organs, a condition referred to as metastatic.

Trial ID:

2025-524095-27-00

Protocol code:

GS-US-742-7757

Trial Phase:

Therapeutic exploratory (Phase II)

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Study of denikitug alone or with drug combination in adults with HER2‑negative metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?