A Trial of ONO-4578 Versus Placebo in Combination With Nivolumab and Chemotherapy in Participants With Gastric Cancer, Esophagogastric Junction Cancer, or Esophageal Adenocarcinoma

NCT07818070 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: ONO-4578-03-0012026-526792-27-00
• Study Type: interventional
• Target: 600
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of ONO-4578 in combination nivolumab and chemotherapy in participants with advanced or metastatic gastric cancer, esophagogastric junction cancer, or esophageal adenocarcinoma. Participants will:

• Receive either ONO-4578 with nivolumab and chemotherapy or placebo with nivolumab and chemotherapy.
• Make visits to the clinic for checkups and tests.
• Answer questions about their health throughout the trial.

Conditions

Gastric Cancer; Esophagogastric Junction Cancer; Esophageal Adenocarcinoma

Keywords

ONO-4578; Programmed cell death ligand 1 positive; Human epidermal growth factor 2 negative; Nivolumab; HER2-negative; PD-L1-positive; Advanced Gastroesophageal Junction (GEJ); Adenocarcinoma; Advanced Gastric Adenocarcinoma; Advanced Esophageal Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction (GEJ); Metastatic Esophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  Up to approximately 4 years

• Progression-Free Survival (PFS) per Blinded Independent Central Review (BICR)

  Up to approximately 4 years

Secondary Outcomes (6)

• PFS per Investigator Assessment

  Up to approximately 4 years

• Objective Response Rate (ORR) per BICR

  Up to approximately 4 years

• Duration of Response (DOR) per BICR

  Up to approximately 4 years

• Disease Control Rate (DCR) per BICR

  Up to approximately 4 years

• Time to Response (TTR) per BICR

  Up to approximately 4 years

Study Arms (2)

ONO-4578 + Nivolumab + Chemotherapy

EXPERIMENTAL

Participants will receive nivolumab and chemotherapy, which will include some of the listed agents.

Drug: ONO-4578; Drug: Nivolumab; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Tegafur-gimeracil-oteracil potassium (S-1); Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Levoleucovorin

Placebo + Nivolumab + Chemotherapy

ACTIVE COMPARATOR

Participants will receive placebo and chemotherapy, which will include some of the listed agents.

Other: Placebo; Drug: Nivolumab; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Tegafur-gimeracil-oteracil potassium (S-1); Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Levoleucovorin

Interventions

ONO-4578 DRUG

ONO-4578 will be administered to participants at a specified dose once daily.

ONO-4578 + Nivolumab + Chemotherapy

Placebo OTHER

Matching placebo for ONO-4578 will be administered to participants once daily.

Placebo + Nivolumab + Chemotherapy

Nivolumab DRUG

Nivolumab will be administered to participants at a specified dose on specified days.

ONO-4578 + Nivolumab + Chemotherapy; Placebo + Nivolumab + Chemotherapy

Oxaliplatin DRUG

Oxaliplatin will be administered to participants at a specified dose on specified days.

ONO-4578 + Nivolumab + Chemotherapy; Placebo + Nivolumab + Chemotherapy

Capecitabine DRUG

Capecitabine will be administered to participants at a specified dose on specified days.

ONO-4578 + Nivolumab + Chemotherapy; Placebo + Nivolumab + Chemotherapy

Tegafur-gimeracil-oteracil potassium (S-1) DRUG

S-1 will be administered to participants at a specified dose on specified days.

ONO-4578 + Nivolumab + Chemotherapy; Placebo + Nivolumab + Chemotherapy

Fluorouracil DRUG

Fluorouracil will be administered to participants at a specified dose on specified days.

ONO-4578 + Nivolumab + Chemotherapy; Placebo + Nivolumab + Chemotherapy

Leucovorin Calcium DRUG

Leucovorin Calcium will be administered to participants at a specified dose on specified days.

ONO-4578 + Nivolumab + Chemotherapy; Placebo + Nivolumab + Chemotherapy

Levoleucovorin DRUG

Levoleucovorin will be administered to participants at a specified dose on specified days.

ONO-4578 + Nivolumab + Chemotherapy; Placebo + Nivolumab + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have advanced or metastatic gastric cancer, esophagogastric junction cancer, or esophageal adenocarcinoma that has been histologically confirmed to be predominant adenocarcinoma.
• Have not been treated with systemic anticancer agents for advanced or metastatic gastric cancer, esophagogastric junction cancer, or esophageal adenocarcinoma.
• Participants who have received neoadjuvant or adjuvant therapy may be included if no residual tumors are found after surgery (R0 resection) and if the therapy was completed at least 180 days before the date of recurrence.
• Have measurable or nonmeasurable disease, as defined in Response Evaluation Criteria in Solid Tumors (RECIST) Guideline v1.1, and documented on computed tomography (CT) or magnetic resonance imaging (MRI) images within 42 days before Cycle 1 Day 1 (C1D1).
• Tumor programmed cell death ligand 1 (PD-L1) expression must be confirmed as combined positive score (CPS ≥1) prior to randomization.
• Participant must be able to provide tissues samples for analyses.

You may not qualify if:

• Participants with Human epidermal growth factor 2 (HER2)-positive or indeterminate gastric cancer, esophagogastric junction cancer, or esophageal adenocarcinoma as determined by local testing. Determination for HER2 positivity is made based on the reference in each site. If there is no reference, rough indication for positive is 3+ by immunohistochemistry (IHC), or 2+ by IHC and positive by in situ hybridization.
• Participants whose tumors have known microsatellite instability-high or mismatch repair-deficient status.
• Marked malnutrition requiring continuous enteral nutrition or intravenous hyperalimentation, or continuous infusion therapy with hospitalization.
• Active autoimmune disease, or history of autoimmune disease that might recur, that may affect vital organ function, or that may require immune-suppressive treatment, including systemic corticosteroids.
• Participants with vitiligo, type 1 diabetes mellitus, and Hashimoto thyroiditis on appropriate replacement therapy may be enrolled.

Sponsors & Collaborators

• Ono Pharmaceutical Co., Ltd.: lead
• Deciphera Pharmaceuticals, LLC: collaborator

MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma Of Esophagus; Adenocarcinoma

Interventions

Nivolumab; Oxaliplatin; Capecitabine; S 1 (combination); Fluorouracil; Leucovorin; Levoleucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Clinical Team

  Ono Pharmaceutical Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Clinical Team

CONTACT

888-724-3274; clinicaltrials@deciphera.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2026
• First Posted: September 14, 2026
• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2031
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share