Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Hepatocellular Carcinoma, Non-Small Cell Lung Cancer
Conditions
Keywords
metastatic, advanced, immuno-oncology, vascular endothelial growth factor (VEGF), angiogenesis, PD-1, PD-L1
Brief summary
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).
Interventions
DRUGRamucirumab
Administered IV
DRUGMEDI4736
Administered IV
Sponsors
AstraZeneca
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Dose Limiting Toxicities (DLTs) | Cycle 1 (up to 28 days) |
Secondary
| Measure | Time frame |
|---|---|
| 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) |
| 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) |
| 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) |
| Overall Survival (OS) | Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months) |
Countries
France, Germany, Israel, Italy, South Korea, Spain, Taiwan, United States
Outcome results
None listed