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

Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Arms in Part 1 received treatment in parallel. Part 1 and Part 2 were sequential assignment.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1: Arm A: DEN (Dose A) and NIVO 		Participants will receive DEN Dose A as an IV infusion in combination with NIVO as an IV infusion.
  • Drug: Denikitug
    Administered Intravenously
    Other names:
    • GS-1811
  • Drug: Nivolumab
    Administered Intravenously
Experimental
Part 1: Arm B: DEN (Dose B) and NIVO 		Participants will receive DEN Dose B as an IV infusion in combination with NIVO as an IV infusion.
  • Drug: Denikitug
    Administered Intravenously
    Other names:
    • GS-1811
  • Drug: Nivolumab
    Administered Intravenously
Experimental
Part 1: Arm C: DEN (Dose B) 		Participants will receive DEN Dose B as an IV infusion.
  • Drug: Denikitug
    Administered Intravenously
    Other names:
    • GS-1811
Experimental
Part 2: Arm D: Safety Run-in (SRI) Cohort 		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.
  • Drug: Denikitug
    Administered Intravenously
    Other names:
    • GS-1811
  • Drug: Ramucirumab
    Administered Intravenously
  • Drug: Paclitaxel
    Administered Intravenously
Experimental
Part 2: Arm D: Expansion Cohort 		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.
  • Drug: Denikitug
    Administered Intravenously
    Other names:
    • GS-1811
  • Drug: Ramucirumab
    Administered Intravenously
  • Drug: Paclitaxel
    Administered Intravenously

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Gilead Sciences

Study Contact

Gilead Clinical Study Information Center
1-833-445-3230 (GILEAD-0)
GileadClinicalTrials@gilead.com