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).
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.
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).
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).
Parallel
Denikitug
DrugAdministered Intravenously
Nivolumab
DrugAdministered Intravenously
Ramucirumab
DrugAdministered Intravenously
Paclitaxel
DrugAdministered Intravenously
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.
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.
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.
Overall Survival (OS)
OS is defined as the length of time from first dose until the date of death from any cause.
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
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