Clinical Trials /

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

NCT02572687

Description:

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).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Hepatocellular Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Ramucirumab (LY3009806) Plus MEDI4736 in Participants With Advanced Gastrointestinal or Thoracic Malignancies
  • Official Title: An Open-Label, Multicenter, Phase 1 Study of Ramucirumab Plus MEDI4736 in Patients With Locally Advanced and Unresectable or Metastatic Gastrointestinal or Thoracic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 16116
  • SECONDARY ID: I4T-MC-JVDJ
  • SECONDARY ID: 2015-003013-14
  • NCT ID: NCT02572687

Conditions

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

Interventions

DrugSynonymsArms
RamucirumabLY3009806, IMC-11121B, CyramzaRamucirumab + MEDI4736 (NSCLC)
MEDI4736Ramucirumab + MEDI4736 (NSCLC)

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Ramucirumab + MEDI4736 (NSCLC)ExperimentalIn 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.
  • Ramucirumab
  • MEDI4736
Ramucirumab + MEDI4736 (Gastric/GEJ)ExperimentalIn 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.
  • Ramucirumab
  • MEDI4736
Ramucirumab + MEDI4736 (HCC)ExperimentalIn 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.
  • Ramucirumab
  • MEDI4736

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame:Cycle 1 (up to 28 days)
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • metastatic
  • advanced
  • immuno-oncology
  • vascular endothelial growth factor (VEGF)
  • angiogenesis
  • PD-1
  • PD-L1

Last Updated

August 18, 2017