HER2-negativePhase 2NCT07546812
Study of Denikitug (GS-1811) Given Alone or With Nivolumab or Chemotherapy in Adults With Metastatic Gastric, Gastroesophageal Junction (GEJ), and Esophageal Adenocarcinomas
A Phase 2 study testing Denikitug, Nivolumab and Ramucirumab in people with HER2-negative and Gastroesophageal Junction, run by Gilead Sciences at 15 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-negative, Gastroesophageal Junction, Esophageal Adenocarcinoma
- What is being tested?
- Denikitug, Nivolumab and Ramucirumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 7 Aug 2026to Jan 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
15 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
Gilead Clinical Study Information Center contact
15 sites in 5 countries
Australia5 sites, 5 recruiting
- Recruiting
Flinders Medical Centre
Bedford Park, South Australia, 5042
- Recruiting
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
- Recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
- Recruiting
Hollywood Private Hospital
Nedlands, Western Australia, 6009
- Recruiting
Royal North Shore Hospital
St Leonards, New South Wales, 2065
United States4 sites, 3 recruiting
- Recruiting
New York Oncology Hematology
Albany, New York, 12206
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Active, not recruiting
Dana Farber Cancer Institute (DFCI)
Boston, Massachusetts, 02215
- Recruiting
Weill Cornell Medicine - New York Presbyterian Hospital
New York, New York, 10021
Spain3 sites, 3 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 8035
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
- Recruiting
Hospital Clinico Universitario de Valencia
Valencia, 46010
France2 sites, 2 recruiting
- Recruiting
Centre Leon Berard, department of medical oncology
Lyon, 69008
- Recruiting
Institut Paoli-Calmettes, department of medical oncology
Marseille, 13009
South Korea1 site, 1 recruiting
- Recruiting
Seoul National University Hospital
Seoul, 03830
About this study
Official 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
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
- Being tested
- Denikitug, Nivolumab, Ramucirumab, Paclitaxel
- Medical subject headings
- Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenikitugDrug
Also called GS-1811
Administered Intravenously
NivolumabDrug
Administered Intravenously
RamucirumabDrug
Administered Intravenously
PaclitaxelDrug
Administered Intravenously
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Denikitug; Drug: Nivolumab |
| Part 1: Arm C: DEN (Dose B) | Experimental | Participants will receive DEN Dose B as an IV infusion. Receives: 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. Receives: 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. Receives: Drug: Denikitug; Drug: Ramucirumab; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 4 years
Secondary outcomes (9)
Duration of Response (DOR)
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.
Measured: Up to 4 years
Progression-Free Survival (PFS)
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.
Measured: Up to 4 years
Overall Survival (OS)
OS is defined as the length of time from first dose until the date of death from any cause.
Measured: 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
Measured: 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
Measured: First dose date up to 120 days post last dose, up to 4 years.
Pharmacokinetic (PK) Parameter: Serum concentration of DEN
Measured: Up to 4 years
PK Parameter: Cmax for Denikitug
Cmax is defined as the maximum observed concentration.
Measured: Up to 4 years
PK Parameter: AUCall for Denikitug
AUCall is defined as the cumulative areas under the curve for all time points.
Measured: Up to 4 years
Percentage of Participants who Developed Treatment-Emergent Antidrug Antibody (ADA) Against Denikitug
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2026
- Study start7 Aug 2026
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-negativeStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Arms in Part 1 received treatment in parallel. Part 1 and Part 2 were sequential assignment.
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07546812
- Sponsor's protocol ID
- GS-US-742-7757
- Other IDs
- 2025-524095-27, CTR20263204, 2025
- Status last verified
- Sep 2026
- First submitted
- 17 Apr 2026
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT07546812
- Acronym / sponsor ID
- GS-US-742-7757
- Conditions
- HER2-negative, Gastroesophageal Junction, Esophageal Adenocarcinoma, Gastric Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2026 (actual)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 23 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Arms in Part 1 received treatment in parallel. Part 1 and Part 2 were sequential assignment.
| Arm | Type | Receives |
|---|---|---|
| Part 1: Arm A: DEN (Dose A) and NIVO | Experimental | Drug: Denikitug, Drug: NivolumabParticipants will receive DEN Dose A as an IV infusion in combination with NIVO as an IV infusion. |
| Part 1: Arm B: DEN (Dose B) and NIVO | Experimental | Drug: Denikitug, Drug: NivolumabParticipants will receive DEN Dose B as an IV infusion in combination with NIVO as an IV infusion. |
| Part 1: Arm C: DEN (Dose B) | Experimental | Drug: DenikitugParticipants will receive DEN Dose B as an IV infusion. |
| Part 2: Arm D: Safety Run-in (SRI) Cohort | Experimental | Drug: Denikitug, Drug: Ramucirumab, Drug: PaclitaxelParticipants 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. |
| Part 2: Arm D: Expansion Cohort | Experimental | Drug: Denikitug, Drug: Ramucirumab, Drug: PaclitaxelIf 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
- Have adequate organ function.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenikitugAlso: GS-1811Administered Intravenously | Drug | 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 |
| NivolumabAdministered Intravenously | Drug | Part 1: Arm A: DEN (Dose A) and NIVO, Part 1: Arm B: DEN (Dose B) and NIVO |
| RamucirumabAdministered Intravenously | Drug | Part 2: Arm D: Expansion Cohort, Part 2: Arm D: Safety Run-in (SRI) Cohort |
| PaclitaxelAdministered Intravenously | Drug | Part 2: Arm D: Expansion Cohort, Part 2: Arm D: Safety Run-in (SRI) Cohort |
Primary outcome
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.
9 secondary outcomes
Duration of Response (DOR)
Time frame: Up to 4 years
Progression-Free Survival (PFS)
Time frame: Up to 4 years
Overall Survival (OS)
Time frame: 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
Time frame: 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
Time frame: First dose date up to 120 days post last dose, up to 4 years.
Pharmacokinetic (PK) Parameter: Serum concentration of DEN
Time frame: Up to 4 years
PK Parameter: Cmax for Denikitug
Time frame: Up to 4 years
PK Parameter: AUCall for Denikitug
Time frame: Up to 4 years
Percentage of Participants who Developed Treatment-Emergent Antidrug Antibody (ADA) Against Denikitug
Time frame: Up to 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Gilead Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Gilead Clinical Study Information Center contact
Gilead Study Director study director
Gilead Sciences
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denikitug, Nivolumab and Ramucirumab in people with HER2-negative and Gastroesophageal Junction, run by Gilead Sciences at 15 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Australia, United States, Spain, France, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gilead Clinical Study Information Center (1-833-445-3230 (GILEAD-0), GileadClinicalTrials@gilead.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.