A Study of Ramucirumab (LY3009806) Plus MEDI4736 in Participants With Advanced Gastrointestinal or Thoracic Malignancies

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety of ramucirumab plus MEDI4736 in participants with locally advanced and unresectable or metastatic gastrointestinal or thoracic malignancies including gastric or gastroesophageal junction (GEJ) adenocarcinoma, non-small cell lung cancer (NSCLC), or hepatocellular carcinoma (HCC).

Official Title
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An Open-Label, Multicenter, Phase 1 Study of Ramucirumab Plus MEDI4736 in Patients With Locally Advanced and Unresectable or Metastatic Gastrointestinal or Thoracic Malignancies

Conditions
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Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Ramucirumab
* Drug: MEDI4736


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Measurable metastatic disease or locally advanced and unresectable disease Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 1-2 prior lines of systemic therapy Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 1-3 prior lines of systemic therapy Has histopathologically or cytologically confirmed HCC, Child-Pugh Class A, with documented disease progression during or after discontinuation of sorafenib therapy, or intolerance of sorafenib therapy, and an α-fetoprotein (AFP) ≥ 1.5x upper limit of normal Availability of tumor tissue for biomarker analysis Has an Eastern Cooperative Oncology Group Performance Status of 0 or 1 Has adequate organ function Exclusion Criteria: Has known brain metastases Has a history of prior cancers not included in this study that were either not treated with curative intent or have been active within the past 5 years History of allogeneic organ transplant Has active or prior documented autoimmune disease within the past 24 months Has human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness, or a history of immunodeficiency Has active hepatitis B or hepatitis C infection, or co-infection with both hepatitis B and C virus For gastric/GEJ and NSCLC participants, has chronic hepatitis B or hepatitis C infection. (For HCC participants, those with chronic hepatitis B virus [HBV] infection with a negative HBV deoxyribonucleic acid [DNA] test and who are on antiviral therapy, and those with chronic hepatitis C virus [HCV] infection are eligible) Has a history of interstitial lung disease, idiopathic pulmonary fibrosis, pneumoconiosis, non-infections pneumonitis, radiation-induced or drug-induced pneumonitis Has received any previous systemic therapy targeting programmed death (PD) 1 or PD-ligand 1/2 signaling pathways, and other immune checkpoint inhibitors Have received previous systemic therapy with ramucirumab

Ages Eligible for Study
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Minimum Age: 18 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: Ramucirumab + MEDI4736 (NSCLC)<br>In phase 1a (DLT phase), ramucirumab plus MEDI4736 given intravenously (IV) every 3 weeks (q3w) of a 21 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met. In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q3w. Participants may continue to receive study treatment until discontinuation criteria are met. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: MEDI4736<br>* Administered IV<br>|
| Experimental: Ramucirumab + MEDI4736 (Gastric/GEJ)<br>In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV every 2 weeks (q2w) of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met. In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: MEDI4736<br>* Administered IV<br>|
| Experimental: Ramucirumab + MEDI4736 (HCC)<br>In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV q2w of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met. In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: MEDI4736<br>* Administered IV<br>|

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) |  | Cycle 1 (up to 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with a Best Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) |  | Baseline to Disease Progression (Approximately 22 Months) | 
| Proportion of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) |  | Baseline to Disease Progression (Approximately 22 Months) | 
| Duration of Response (DoR) |  | Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 22 Months) | 
| Time to First Response (TTR) |  | Baseline to Date of CR or PR (Approximately 22 Months) | 
| Progression Free Survival (PFS) |  | Baseline to Progressive Disease or Death from Any Cause (Approximately 22 Months) | 
| Overall Survival (OS) |  | Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months) | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab and MEDI4736 |  | Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months) | 
| PK: Minimum Concentration (Cmin) of Ramucirumab and MEDI4736 |  | Predose Cycle 1 Day 1 through Follow up (Approximately 22 Months) | 
| Number of Participants with Treatment Emergent Anti Ramucirumab Antibodies |  | Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months) | 
| Number of Participants with Treatment Emergent Anti MEDI4736 Antibodies |  | Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, advanced, immuno-oncology, vascular endothelial growth factor (VEGF), angiogenesis, PD-1, PD-L1