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

January 18, 2021 updated by: Eli Lilly and Company

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

85

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Besancon Cedex, France, 25030
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Marseille Cedex 5, France, 13385
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Montpellier Cedex 5, France, 34298
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Saint Etienne Cedex 2, France, 42055
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Germany
      • Großhansdorf, Germany, 22927
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Israel
      • Jerusalem, Israel, 9112001
        • Hadassah Medical Center - Ein Karem
      • Ramat Gan, Israel, 5266202
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Tel Aviv, Israel, 6423906
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Italy
      • Milano, Italy, 20133
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Rozzano, Italy, 20089
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Korea, Republic of
      • Seoul, Korea, Republic of, 06351
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Seoul, Korea, Republic of, 03080
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
      • Seoul, Korea, Republic of, 05505
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
      • Seoul, Korea, Republic of, 03722
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
  • Spain
      • Madrid, Spain, 28040
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Malaga, Spain, 29010
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Sevilla, Spain, 41013
        • Hospital Virgen del Rocío
  • Taiwan
      • Tainan, Taiwan, 70403
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Tainan, Taiwan, 704
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
      • Tainan, Taiwan, 73657
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
      • Taipei, Taiwan, 10048
        • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • United States
    • California
      • Santa Monica, California, United States, 90404
        • UCLA Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Johns Hopkins University
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Carolinas Medical Center
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • The Miriam Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6307
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ramucirumab + MEDI4736 (NSCLC)

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
Administered IV
Other Names:
  • LY3009806
  • Cyramza
  • IMC-11121B
Drug: MEDI4736
Administered IV
Experimental: Ramucirumab + MEDI4736 (Gastric/GEJ)

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
Administered IV
Other Names:
  • LY3009806
  • Cyramza
  • IMC-11121B
Drug: MEDI4736
Administered IV
Experimental: Ramucirumab + MEDI4736 (HCC)

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
Administered IV
Other Names:
  • LY3009806
  • Cyramza
  • IMC-11121B
Drug: MEDI4736
Administered IV

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
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)
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)
Time Frame: Baseline to Disease Progression (Approximately 22 Months)
Baseline to Disease Progression (Approximately 22 Months)
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)
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)
Time Frame: Baseline to Date of CR or PR (Approximately 22 Months)
Baseline to Date of CR or PR (Approximately 22 Months)
Progression Free Survival (PFS)
Time Frame: Baseline to Progressive Disease or Death from Any Cause (Approximately 22 Months)
Baseline to Progressive Disease or Death from Any Cause (Approximately 22 Months)
Overall Survival (OS)
Time Frame: Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months)
Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab and MEDI4736
Time Frame: Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)
Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)
PK: Minimum Concentration (Cmin) of Ramucirumab and MEDI4736
Time Frame: Predose Cycle 1 Day 1 through Follow up (Approximately 22 Months)
Predose Cycle 1 Day 1 through Follow up (Approximately 22 Months)
Number of Participants with Treatment Emergent Anti Ramucirumab Antibodies
Time Frame: Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)
Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)
Number of Participants with Treatment Emergent Anti MEDI4736 Antibodies
Time Frame: Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)
Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Collaborators

AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 19, 2016

Primary Completion (Actual)

March 27, 2018

Study Completion (Actual)

January 13, 2021

Study Registration Dates

First Submitted

October 7, 2015

First Submitted That Met QC Criteria

October 8, 2015

First Posted (Estimate)

October 9, 2015

Study Record Updates

Last Update Posted (Actual)

January 20, 2021

Last Update Submitted That Met QC Criteria

January 18, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16116
  • I4T-MC-JVDJ (Other Identifier: Eli Lilly and Company)
  • 2015-003013-14 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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