A Study of Ramucirumab Plus Pembrolizumab in Participants With Gastric or GEJ Adenocarcinoma, NSCLC, Transitional Cell Carcinoma of the Urothelium, or Biliary Tract Cancer

August 17, 2022 updated by: Eli Lilly and Company

An Open-Label, Multicenter, Phase 1 Study of Ramucirumab Plus Pembrolizumab in Patients With Locally Advanced and Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer, Transitional Cell Carcinoma of the Urothelium, or Biliary Tract Cancer

The main purpose of this study is to evaluate the safety and preliminary efficacy of the combination of the study drug known as ramucirumab plus pembrolizumab in participants with locally advanced and unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, non-small cell lung cancer (NSCLC), transitional cell carcinoma of the urothelium, or biliary tract cancer (BTC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

298

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
      • Dijon Cedex, France, 21034
        • 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.
      • Lille Cedex, France, 59020
        • 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.
      • Lyon Cedex 08, France, 69373
        • 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.
      • Paris CEDEX 05, France, 75248
        • 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
      • Dresden, Germany, 01307
        • 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.
      • Heidelberg, Germany, 69126
        • 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.
      • Tübingen, Germany, 72076
        • 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.
  • Japan
      • Kochi-Shi, Japan, 780-0051
        • 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.
      • Yamanashi, Japan, 400-0124
        • 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
      • Barcelona, Spain, 08035
        • 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.
      • Madrid, Spain, 28050
        • 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.
      • Pamplona, Spain, 31008
        • 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 Kingdom
      • London, United Kingdom, W1G 6AD
        • 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.
      • Manchester, United Kingdom, M20 4BX
        • 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.
      • Sutton, United Kingdom, SM2 5PT
        • 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
    • Connecticut
      • New Haven, Connecticut, United States, 06520-8020
        • Yale University School of Medicine
    • Florida
      • Fort Myers, Florida, United States, 33916
        • Florida Cancer Specialists
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists and Research Institute
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology PLLC
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology PLLC
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute SCRI
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance

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:

  • Metastatic disease or locally advanced, unresectable disease.

    • Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 0-2 prior lines of systemic therapy
    • Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 0-3 prior lines of systemic therapy
    • Has histopathologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis) with documented disease progression after 1-3 prior lines of systemic therapy
    • Has histologically confirmed biliary tract adenocarcinoma with documented progression after 1-2 prior lines of systemic therapy
  • Availability of tumor tissue for biomarker analysis from a newly obtained core or excisional biopsy or willing to undergo a tumor biopsy. For first line NSCLC participants only, PD-L1 expression should be 1% or higher.
  • Have an Eastern Cooperative Oncology Group Performance Status of 0 or 1.
  • Has adequate organ function.
  • Have an anticipated life expectancy of ≥3 months.

Exclusion Criteria:

  • Have known brain metastases.
  • Has received ≥3 lines of prior systemic therapy for gastric or GEJ adenocarcinoma and BTC or ≥4 lines for NSCLC or urothelial cancer.
  • Has active autoimmune disease.
  • Known human immunodeficiency virus (HIV) infection.
  • Known active hepatitis B or hepatitis C infection.
  • Has received any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or VEGF receptor, or programmed death (PD) 1 or PD-ligand 1/2 signaling pathways.
  • Have received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines that do not contain live virus are permitted.
  • Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment.
  • Have an elective or a planned major surgery during the course of the trial or has undergone major surgery within 28 days prior to enrollment.

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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ramucirumab + Pembrolizumab (Phase 1a Schedule 1)
Gastric-GEJ, BTC: Ramucirumab given intravenously (IV) on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza
EXPERIMENTAL: Ramucirumab + Pembrolizumab (Phase 1a Schedule 2)
Gastric, NSCLC, Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza
EXPERIMENTAL: Ramucirumab + Pembrolizumab (Phase 1b Cohort A)
Gastric-GEJ: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza
EXPERIMENTAL: Ramucirumab + Pembrolizumab (Phase 1b Cohort A1)
BTC: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza
EXPERIMENTAL: Ramucirumab + Pembrolizumab (Phase 1b Cohort A2)
Gastric-GEJ (first line only): Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza
EXPERIMENTAL: Ramucirumab + Pembrolizumab (Phase 1b Cohort B)
Gastric-GEJ: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza
EXPERIMENTAL: Ramucirumab + Pembrolizumab (Phase 1b Cohort C)
NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza
EXPERIMENTAL: Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort D)
Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza
EXPERIMENTAL: Ramucirumab + Pembrolizumab (Phase 1b Cohort E)
NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.
Drug: Pembrolizumab
Administered IV
Other Names:
  • MK3475
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time Frame: Baseline to Measured Progressive Disease (Estimated up to 24 Months)
Baseline to Measured Progressive Disease (Estimated up to 24 Months)

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of Participants Who Achieve Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Time Frame: Baseline to Measured Progressive Disease (Estimated up 24 Months)
Baseline to Measured Progressive Disease (Estimated up 24 Months)
Proportion of Participants who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]
Time Frame: Baseline to Measured Progressive Disease (Estimated up 24 Months)
Baseline to Measured Progressive Disease (Estimated up 24 Months)
Duration of Response (DoR)
Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up 24 Months)
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up 24 Months)
Time to First Response (TTR)
Time Frame: Baseline to Date of CR or PR (Estimated up 24 Months)
Baseline to Date of CR or PR (Estimated up 24 Months)
Progression Free Survival (PFS)
Time Frame: Baseline to Progressive Disease or Death of Any Cause (Estimated up 24 Months)
Baseline to Progressive Disease or Death of Any Cause (Estimated up 24 Months)
Overall Survival (OS)
Time Frame: Baseline to Death from Any Cause (Estimated up 24 Months)
Baseline to Death from Any Cause (Estimated up 24 Months)
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Time Frame: Predose Day 1 Cycle 1 through Cycle 9 Day 1 (21 Day Cycles)
Predose Day 1 Cycle 1 through Cycle 9 Day 1 (21 Day Cycles)

Collaborators and Investigators

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

Sponsor

Eli Lilly and Company

Collaborators

Merck Sharp & Dohme LLC

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.

General Publications

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)

July 29, 2015

Primary Completion (ACTUAL)

August 31, 2018

Study Completion (ACTUAL)

April 12, 2022

Study Registration Dates

First Submitted

May 11, 2015

First Submitted That Met QC Criteria

May 11, 2015

First Posted (ESTIMATE)

May 13, 2015

Study Record Updates

Last Update Posted (ACTUAL)

August 18, 2022

Last Update Submitted That Met QC Criteria

August 17, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15787
  • I4T-MC-JVDF (OTHER: Eli Lilly and Company)
  • 2015-001473-40 (EUDRACT_NUMBER)
  • KEYNOTE -098 (OTHER: Merck)

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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