Study Details

OVERVIEW

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

PROTOCOL 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).

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

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

Gender

N/A

Date

May 2026 - January 2030

Study Type

INTERVENTIONAL

Study Phase

PHASE2

Product

Denikitug, Nivolumab, Ramucirumab, Paclitaxel

Eligibility Information

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.

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.

Locations

Locations (1)

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia, 2050

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