A Phase 1/2 Study of Ramucirumab Plus Nivolumab in Participants With Gastric or GEJ Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and efficacy of the combination therapy of ramucirumab and nivolumab in participants with advanced or recurrent unresectable gastric or GEJ cancer.

Official Title
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A Multicenter, Phase 1/2 Study of Ramucirumab Plus Nivolumab as Second-line Therapy in Participants With Gastric or GEJ Cancer

Conditions
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Gastric Cancer, Gastroesophageal Junction Region (GEJ) Cancer

Intervention / Treatment
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* Biological: Ramucirumab
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced or recurrent unresectable gastric or GEJ cancer Histologically confirmed adenocarcinoma (papillary adenocarcinoma, tubular adenocarcinoma or poorly differentiated adenocarcinoma), signet-ring cell carcinoma, mucinous adenocarcinoma or hepatoid adnocarcinoma Patients with normal oral intake Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Patients who have measurable target lesion Patients has a refractory or intolerant pretreatment by pyrimidine fluoride anticancer agent and platinum-based anticancer agent Patients with adequate organ function Patients with no pretreatment history including ramucirumab, nivolumab or other therapies targeting control of T cells Patients with written informed consent Exclusion Criteria: Patients have double cancer Patients have infection required systemic therapy Known central vervous system (CNS) metastasis Patients with history of pneumonitis or pulmonary fibrosis Patients with history of serious anaphylaxis induced by antibody preparation Patients who have known active autoimmune disease or history of chronic recurrent autoimmune disease Female who is pregnant, lactating or suspected pregnancy Patients with psychosis or dementia to interfere to obtain informed consent appropriately

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1<br>Ramucirumab: 8 mg/kg, every two week Nivolumab: 3.0 mg/kg or 1.0 mg/kg (optional), every two weeks | Biological: Ramucirumab<br>* Ramucirumab (8 mg/kg) is administered.<br>* Other names: LY3009806;Biological: Nivolumab<br>* Nivolumab (3.0 mg/kg or 1.0 mg/kg) is administered.<br>* Other names: ONO-4538;|
| Experimental: Phase 2<br>Ramucirumab: 8 mg/kg, every two week Nivolumab: recommended dose established in the phase 1, every two weeks | Biological: Ramucirumab<br>* Ramucirumab (8 mg/kg) is administered.<br>* Other names: LY3009806;Biological: Nivolumab<br>* Nivolumab (3.0 mg/kg or 1.0 mg/kg) is administered.<br>* Other names: ONO-4538;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities (DLTs) | Number of participants with dose limiting toxicities (DLTs) | Phase 1, course 1 (up to 28 days) | 
| Progression free survival rate after 6 months | Progression free survival rate after 6 months | from baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Number of participants with adverse events | from baseline to date of treatment cessation, approximately 24 months | 
| Objective response rate (ORR) | percentage of participants with with a best response of complete response (CR) or partial response (PR) | from baseline to date of disease progression, approximately 24 months | 
| Disease control rate (DCR) | percentage of participants with with a best response of CR, PR or stable disease (SD) | from baseline to date of disease progression, approximately 24 months | 
| Overall survival (OS) | Overall survival (OS) | from baseline to date of death, approximately 24 months | 
| Progression free survival (PFS) | Progression free survival (PFS) | from baseline to date of disease progression or death, approximately 24 months |