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

NCT ID: NCT02443324

Last Updated: 2024-07-31

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

175 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-29

Study Completion Date

2022-04-12

Brief Summary

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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).

Detailed Description

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Conditions

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Gastric Adenocarcinoma Adenocarcinoma of the Gastroesophageal Junction Non-small Cell Lung Cancer Carcinoma, Transitional Cell Biliary Tract Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A

Participants with gastroesophageal junction (GEJ) cancer \[Second-Third Line (L)\] received 8 milligrams per kilogram (mg/kg) ramucirumab given intravenously (IV) on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 for every 3 weeks (Q3W) of a 21-day cycle.

Group Type EXPERIMENTAL

Ramucirumab

Intervention Type DRUG

Administered IV

Pembrolizumab

Intervention Type DRUG

Administered IV

Cohort A1

Participants with BTC cancer (Second-Third L) received 8 mg/kg ramucirumab given IV on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Group Type EXPERIMENTAL

Ramucirumab

Intervention Type DRUG

Administered IV

Cohort A2

Participants with Gastric-GEJ cancer (First L) received 8 mg/kg ramucirumab given IV on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Group Type EXPERIMENTAL

Ramucirumab

Intervention Type DRUG

Administered IV

Pembrolizumab

Intervention Type DRUG

Administered IV

Cohort B

Participants with Gastric-GEJ cancer (Second-Third L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Group Type EXPERIMENTAL

Ramucirumab

Intervention Type DRUG

Administered IV

Pembrolizumab

Intervention Type DRUG

Administered IV

Cohort C

Participants with NSCLC (Second-Fourth L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Group Type EXPERIMENTAL

Ramucirumab

Intervention Type DRUG

Administered IV

Pembrolizumab

Intervention Type DRUG

Administered IV

Cohort D

Participants with Urothelial cancer (Second-Fourth L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Group Type EXPERIMENTAL

Ramucirumab

Intervention Type DRUG

Administered IV

Pembrolizumab

Intervention Type DRUG

Administered IV

Cohort E

Participants with NSCLC cancer (First L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.

Group Type EXPERIMENTAL

Ramucirumab

Intervention Type DRUG

Administered IV

Pembrolizumab

Intervention Type DRUG

Administered IV

Interventions

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Ramucirumab

Administered IV

Intervention Type DRUG

Pembrolizumab

Administered IV

Intervention Type DRUG

Other Intervention Names

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LY3009806 IMC-1121B Cyramza MK3475

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists and Research Institute

St. Petersburg, Florida, United States

Site Status

Tennessee Oncology PLLC

Chattanooga, Tennessee, United States

Site Status

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, United States

Site Status

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

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.

Dijon, , France

Site Status

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, , France

Site Status

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, , France

Site Status

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, , France

Site Status

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.

Dresden, , Germany

Site Status

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

Site Status

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

Site Status

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.

Kochi, , Japan

Site Status

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

Site Status

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.

Barcelona, , Spain

Site Status

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

Site Status

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

Site Status

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.

London, , United Kingdom

Site Status

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

Site Status

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

Site Status

Countries

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United States France Germany Japan Spain United Kingdom

References

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Herbst RS, Arkenau HT, Bendell J, Arrowsmith E, Wermke M, Soriano A, Penel N, Santana-Davila R, Bischoff H, Chau I, Mi G, Wang H, Rasmussen E, Ferry D, Chao BH, Paz-Ares L. Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. J Thorac Oncol. 2021 Feb;16(2):289-298. doi: 10.1016/j.jtho.2020.10.004. Epub 2020 Oct 15.

Reference Type DERIVED
PMID: 33068794 (View on PubMed)

Herbst RS, Arkenau HT, Santana-Davila R, Calvo E, Paz-Ares L, Cassier PA, Bendell J, Penel N, Krebs MG, Martin-Liberal J, Isambert N, Soriano A, Wermke M, Cultrera J, Gao L, Widau RC, Mi G, Jin J, Ferry D, Fuchs CS, Petrylak DP, Chau I. Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. Lancet Oncol. 2019 Aug;20(8):1109-1123. doi: 10.1016/S1470-2045(19)30458-9. Epub 2019 Jul 10.

Reference Type DERIVED
PMID: 31301962 (View on PubMed)

Arkenau HT, Martin-Liberal J, Calvo E, Penel N, Krebs MG, Herbst RS, Walgren RA, Widau RC, Mi G, Jin J, Ferry D, Chau I. Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open-Label, Phase I Trial (JVDF). Oncologist. 2018 Dec;23(12):1407-e136. doi: 10.1634/theoncologist.2018-0044. Epub 2018 May 31.

Reference Type DERIVED
PMID: 29853658 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://trials.lilly.com/en-US/trial/98852

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

Other Identifiers

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I4T-MC-JVDF

Identifier Type: OTHER

Identifier Source: secondary_id

2015-001473-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KEYNOTE -098

Identifier Type: OTHER

Identifier Source: secondary_id

15787

Identifier Type: -

Identifier Source: org_study_id

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