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

Primary Purpose

Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Ramucirumab

MEDI4736

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring metastatic, advanced, immuno-oncology, vascular endothelial growth factor (VEGF), angiogenesis, PD-1, PD-L1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

UCLA Medical Center
Johns Hopkins University
Washington University Medical Center
Carolinas Medical Center
The Miriam Hospital
Vanderbilt University Medical Center
University of Texas MD Anderson Cancer Center
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.
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.
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.
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.
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.
Hadassah Medical Center - Ein Karem
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.
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.
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.
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.
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
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
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
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.
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.
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.
Hospital Virgen del Rocío
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.
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.
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
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Ramucirumab + MEDI4736 (NSCLC)

Ramucirumab + MEDI4736 (Gastric/GEJ)

Ramucirumab + MEDI4736 (HCC)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants with Dose Limiting Toxicities (DLTs)

Secondary Outcome Measures

Percentage of Participants with a Best Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Proportion of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)

Duration of Response (DoR)

Time to First Response (TTR)

Progression Free Survival (PFS)

Overall Survival (OS)

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab and MEDI4736

PK: Minimum Concentration (Cmin) of Ramucirumab and MEDI4736

Number of Participants with Treatment Emergent Anti Ramucirumab Antibodies

Number of Participants with Treatment Emergent Anti MEDI4736 Antibodies

Full Information

NCT ID

NCT02572687

First Posted

October 7, 2015

Last Updated

January 18, 2021

Sponsor

Eli Lilly and Company

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT02572687

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

February 19, 2016 (Actual)

Primary Completion Date

March 27, 2018 (Actual)

Study Completion Date

January 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

85 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ramucirumab + MEDI4736 (NSCLC)

Arm Type

Experimental

Arm Description

Arm Title

Ramucirumab + MEDI4736 (Gastric/GEJ)

Arm Type

Experimental

Arm Description

Arm Title

Ramucirumab + MEDI4736 (HCC)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ramucirumab

Other Intervention Name(s)

LY3009806, IMC-11121B, Cyramza

Intervention Description

Administered IV

Intervention Type

Drug

Intervention Name(s)

MEDI4736

Intervention Description

Administered IV

Primary Outcome Measure Information:

Title

Number of Participants with Dose Limiting Toxicities (DLTs)

Time Frame

Cycle 1 (up to 28 days)

Secondary Outcome Measure Information:

Title

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)

Title

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)

Title

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)

Title

Time to First Response (TTR)

Time Frame

Baseline to Date of CR or PR (Approximately 22 Months)

Title

Progression Free Survival (PFS)

Time Frame

Baseline to Progressive Disease or Death from Any Cause (Approximately 22 Months)

Title

Overall Survival (OS)

Time Frame

Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months)

Title

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab and MEDI4736

Time Frame

Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)

Title

PK: Minimum Concentration (Cmin) of Ramucirumab and MEDI4736

Time Frame

Predose Cycle 1 Day 1 through Follow up (Approximately 22 Months)

Title

Number of Participants with Treatment Emergent Anti Ramucirumab Antibodies

Time Frame

Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)

Title

Number of Participants with Treatment Emergent Anti MEDI4736 Antibodies

Time Frame

Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

UCLA Medical Center

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Johns Hopkins University

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231

Country

United States

Facility Name

Washington University Medical Center

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Carolinas Medical Center

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

The Miriam Hospital

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

02906

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-6307

Country

United States

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

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.

City

Besancon Cedex

ZIP/Postal Code

25030

Country

France

Facility Name

City

Marseille Cedex 5

ZIP/Postal Code

13385

Country

France

Facility Name

City

Montpellier Cedex 5

ZIP/Postal Code

34298

Country

France

Facility Name

City

Saint Etienne Cedex 2

ZIP/Postal Code

42055

Country

France

Facility Name

City

Großhansdorf

ZIP/Postal Code

22927

Country

Germany

Facility Name

Hadassah Medical Center - Ein Karem

City

Jerusalem

ZIP/Postal Code

9112001

Country

Israel

Facility Name

City

Ramat Gan

ZIP/Postal Code

5266202

Country

Israel

Facility Name

City

Tel Aviv

ZIP/Postal Code

6423906

Country

Israel

Facility Name

City

Milano

ZIP/Postal Code

20133

Country

Italy

Facility Name

City

Rozzano

ZIP/Postal Code

20089

Country

Italy

Facility Name

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Facility Name

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

City

Malaga

ZIP/Postal Code

29010

Country

Spain

Facility Name

Hospital Virgen del Rocío

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

Facility Name

City

Tainan

ZIP/Postal Code

70403

Country

Taiwan

Facility Name

City

Tainan

ZIP/Postal Code

704

Country

Taiwan

Facility Name

City

Tainan

ZIP/Postal Code

73657

Country

Taiwan

Facility Name

City

Taipei

ZIP/Postal Code

10048

Country

Taiwan

12. IPD Sharing Statement

Links:

URL

https://trials.lillytrialguide.com/en-US/trial/1MGivPlaAo26qYOuKOGOAe?conditionId=6BrOA7cZt6ESK8AScGGEao

Description

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

Learn more about this trial

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

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