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

Primary Purpose

Gastric Adenocarcinoma, Adenocarcinoma of the Gastroesophageal Junction, Non-small Cell Lung Cancer

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Ramucirumab

Pembrolizumab

About this trial

This is an interventional treatment trial for Gastric Adenocarcinoma focused on measuring immuno-oncology, Vascular Endothelial Growth Factor (VEGF), angiogenesis, PD-1, carcinoma of the bladder, carcinoma of the urethra, carcinoma of the ureter, carcinoma of the renal pelvis, carcinoma of the biliary tract

Eligibility Criteria

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

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.

Sites / Locations

Yale University School of Medicine
Florida Cancer Specialists
Florida Cancer Specialists and Research Institute
Tennessee Oncology PLLC
Sarah Cannon Research Institute SCRI
Tennessee Oncology PLLC
Seattle Cancer Care Alliance
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Arm Label

Ramucirumab + Pembrolizumab (Phase 1a Schedule 1)

Ramucirumab + Pembrolizumab (Phase 1a Schedule 2)

Ramucirumab + Pembrolizumab (Phase 1b Cohort A)

Ramucirumab + Pembrolizumab (Phase 1b Cohort A1)

Ramucirumab + Pembrolizumab (Phase 1b Cohort A2)

Ramucirumab + Pembrolizumab (Phase 1b Cohort B)

Ramucirumab + Pembrolizumab (Phase 1b Cohort C)

Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort D)

Ramucirumab + Pembrolizumab (Phase 1b Cohort E)

Arm Description

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.

Gastric, NSCLC, Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Gastric-GEJ: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

BTC: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

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.

Gastric-GEJ: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Outcomes

Primary Outcome Measures

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

Secondary Outcome Measures

Proportion of Participants Who Achieve Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

Proportion of Participants who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]

Duration of Response (DoR)

Time to First Response (TTR)

Progression Free Survival (PFS)

Overall Survival (OS)

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Full Information

NCT ID

NCT02443324

First Posted

May 11, 2015

Last Updated

August 17, 2022

Sponsor

Eli Lilly and Company

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02443324

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

July 29, 2015 (Actual)

Primary Completion Date

August 31, 2018 (Actual)

Study Completion Date

April 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

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

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

Keywords

immuno-oncology, Vascular Endothelial Growth Factor (VEGF), angiogenesis, PD-1, carcinoma of the bladder, carcinoma of the urethra, carcinoma of the ureter, carcinoma of the renal pelvis, carcinoma of the biliary tract

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

298 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ramucirumab + Pembrolizumab (Phase 1a Schedule 1)

Arm Type

Experimental

Arm Description

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.

Arm Title

Ramucirumab + Pembrolizumab (Phase 1a Schedule 2)

Arm Type

Experimental

Arm Description

Gastric, NSCLC, Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Arm Title

Ramucirumab + Pembrolizumab (Phase 1b Cohort A)

Arm Type

Experimental

Arm Description

Gastric-GEJ: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Arm Title

Ramucirumab + Pembrolizumab (Phase 1b Cohort A1)

Arm Type

Experimental

Arm Description

BTC: Ramucirumab given IV on day 1 and 8 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Arm Title

Ramucirumab + Pembrolizumab (Phase 1b Cohort A2)

Arm Type

Experimental

Arm Description

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.

Arm Title

Ramucirumab + Pembrolizumab (Phase 1b Cohort B)

Arm Type

Experimental

Arm Description

Gastric-GEJ: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Arm Title

Ramucirumab + Pembrolizumab (Phase 1b Cohort C)

Arm Type

Experimental

Arm Description

NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Arm Title

Experimental: Ramucirumab + Pembrolizumab (Phase 1b Cohort D)

Arm Type

Experimental

Arm Description

Urothelial: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Arm Title

Ramucirumab + Pembrolizumab (Phase 1b Cohort E)

Arm Type

Experimental

Arm Description

NSCLC: Ramucirumab given IV on day 1 in combination with pembrolizumab given IV on day 1 of a 21 day cycle.

Intervention Type

Drug

Intervention Name(s)

Ramucirumab

Other Intervention Name(s)

LY3009806, IMC-1121B, Cyramza

Intervention Description

Administered IV

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

MK3475

Intervention Description

Administered IV

Primary Outcome Measure Information:

Title

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

Time Frame

Baseline to Measured Progressive Disease (Estimated up to 24 Months)

Secondary Outcome Measure Information:

Title

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)

Title

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)

Title

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)

Title

Time to First Response (TTR)

Time Frame

Baseline to Date of CR or PR (Estimated up 24 Months)

Title

Progression Free Survival (PFS)

Time Frame

Baseline to Progressive Disease or Death of Any Cause (Estimated up 24 Months)

Title

Overall Survival (OS)

Time Frame

Baseline to Death from Any Cause (Estimated up 24 Months)

Title

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Time Frame

Predose Day 1 Cycle 1 through Cycle 9 Day 1 (21 Day Cycles)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

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

Yale University School of Medicine

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520-8020

Country

United States

Facility Name

Florida Cancer Specialists

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33916

Country

United States

Facility Name

Florida Cancer Specialists and Research Institute

City

Saint Petersburg

State/Province

Florida

ZIP/Postal Code

33705

Country

United States

Facility Name

Tennessee Oncology PLLC

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37404

Country

United States

Facility Name

Sarah Cannon Research Institute SCRI

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Tennessee Oncology PLLC

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Seattle Cancer Care Alliance

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

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

Dijon Cedex

ZIP/Postal Code

21034

Country

France

Facility Name

City

Lille Cedex

ZIP/Postal Code

59020

Country

France

Facility Name

City

Lyon Cedex 08

ZIP/Postal Code

69373

Country

France

Facility Name

City

Paris CEDEX 05

ZIP/Postal Code

75248

Country

France

Facility Name

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

City

Heidelberg

ZIP/Postal Code

69126

Country

Germany

Facility Name

City

Tübingen

ZIP/Postal Code

72076

Country

Germany

Facility Name

City

Kochi-Shi

ZIP/Postal Code

780-0051

Country

Japan

Facility Name

City

Yamanashi

ZIP/Postal Code

400-0124

Country

Japan

Facility Name

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

City

Madrid

ZIP/Postal Code

28050

Country

Spain

Facility Name

City

Pamplona

ZIP/Postal Code

31008

Country

Spain

Facility Name

City

London

ZIP/Postal Code

W1G 6AD

Country

United Kingdom

Facility Name

City

Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

Facility Name

City

Sutton

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

33068794

Citation

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.

Results Reference

derived

PubMed Identifier

31301962

Citation

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.

Results Reference

derived

PubMed Identifier

29853658

Citation

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.

Results Reference

derived

Links:

URL

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

Description

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

Learn more about this trial

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

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