Study of ONO-4538 in Gastric Cancer

Study Overview
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Brief Summary
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The purpose of study is to evaluate the efficacy and safety of ONO-4538 with chemotherapy in unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer) not previously treated with the first-line therapy. Part 1 is intended to evaluate the tolerability, safety, and efficacy of ONO-4538 in combination with SOX therapy (Tegafur / gimeracil / oteracil potassium + Oxaliplatin) or CapeOX therapy (Capecitabine + Oxaliplatin). In part 2, the investigator or the subinvestigator will choose a chemotherapy (SOX or CapeOX therapy), taking into account the condition of each subject. Part 2 is planned to evaluate the efficacy and safety of ONO-4538 + chemotherapy in comparison with placebo + chemotherapy.

Official Title
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ONO-4538 Phase II/III Study A Multicenter, Randomized Study in Patients With Unresectable Advanced or Recurrent Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: ONO-4538
* Drug: Oxaliplatin
* Drug: Tegafur- Gimeracil-Oteracil potassium
* Drug: Capecitabine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer) that has not been treated with the first-line therapy with systemic antitumor agents for advanced or recurrent gastric cancer (including esophagogastric junction cancer) Have measurable lesions as defined in RECIST Guideline Version 1.1 ECOG PS score 0 or 1 Have a life expectancy of at least 3 months Exclusion Criteria: Have multiple cancers Have a current or past history of severe hypersensitivity to any other antibody products Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment Patients with active, known or suspected autoimmune disease

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ONO-4538 + SOX Therapy Cohort (Part 1)<br>ONO-4538 360 mg solution intravenously for 30 min in every 3 weeks. Oxaliplatin 130 mg/m2 (BSA) solution intravenously for 2 hours once-daily, followed by 20 days off. Tegafur-gimeracil-oteracil potassium combination drug 40 - 60 mg bid orally in 14 days, followed by 7 days off Each drug will be continued until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. | Drug: ONO-4538<br> <br> Drug: Oxaliplatin<br> <br> Drug: Tegafur- Gimeracil-Oteracil potassium<br> <br> |
| Experimental: ONO-4538 + CapeOX Therapy Cohort (Part 1)<br>ONO-4538 360 mg solution intravenously for 30 min in every 3 weeks. Oxaliplatin 130 mg/m2 (body surface area) solution intravenously for 2 hours once-daily, followed by 20 days off. Capecitabine 1200 - 2100 mg bid orally in 14 days, followed by 7 days off. Each drug will be continued until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. | Drug: ONO-4538<br> <br> Drug: Oxaliplatin<br> <br> Drug: Capecitabine<br> <br> |
| Experimental: ONO-4538 + chemotherapy group (Part 2)<br>With regard to the ONO-4538 + chemotherapy group, either SOX therapy or CapeOX therapy will be selected as the chemotherapy by the investigator or the subinvestigator, taking into account the condition of each subject. ONO-4538 360 mg solution intravenously for 30 min in every 3 weeks. Oxaliplatin 130 mg/m2 (body surface area) solution intravenously for 2 hours once-daily, followed by 20 days off. Tegafur-gimeracil-oteracil potassium combination drug 40 - 60 mg bid or Capecitabine 1000 mg/ m2 (body surface area) bid orally in 14 days, followed by 7 days off. Each drug will be continued until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. | Drug: ONO-4538<br> <br> Drug: Oxaliplatin<br> <br> Drug: Tegafur- Gimeracil-Oteracil potassium<br> <br> Drug: Capecitabine<br> <br> |
| Placebo Comparator: Placebo + Chemotherapy group (Part 2)<br>With regard to the placebo + chemotherapy group, either SOX therapy or CapeOX therapy will be selected as the chemotherapy by the investigator or the subinvestigator, taking into account the condition of each subject. Placebo solution intravenously for 30 min in every 3 weeks. Oxaliplatin 130 mg/m2 (body surface area) solution intravenously for 2 hours once-daily, followed by 20 days off. Tegafur-gimeracil-oteracil potassium combination drug 40 - 60 mg bid or Capecitabine 1000 mg/ m2 (body surface area) bid orally in 14 days, followed by 7 days off. Each drug will be continued until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. | Drug: Oxaliplatin<br> <br> Drug: Tegafur- Gimeracil-Oteracil potassium<br> <br> Drug: Capecitabine<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (central assessment by IRRC) (only Part 2) |  | Up to study completion (estimated time frame: 48 months) | 
| Overall survival (only Part 2) |  | Up to study completion (estimated time frame: 54 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (only Part 2) |  | Up to study completion (estimated time frame: 54 months) | 
| Progression-free survival (assessment by the site investigator)(only Part 2) |  | Up to study completion (estimated time frame: 54 months) | 
| Duration of response (only Part 2) |  | Up to study completion (estimated time frame: 54 months) | 
| Disease control rate (only Part 2) |  | Up to study completion (estimated time frame: 54 months) | 
| Time to response (only Part 2) |  | Up to study completion (estimated time frame: 54 months) | 
| Best overall response (only Part 2) |  | Up to study completion (estimated time frame: 54 months) | 
| Percent change in the sum of diameters of target lesions (only Part 2) |  | Up to study completion (estimated time frame: 54 months) | 
| Safety will be analyzed through the incidence of adverse events, serious adverse events |  | Up to 28 days from last dose | 
| Safety will be analyzed through the incidence of laboratory abnormalities |  | Up to 28 days from last dose |