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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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02443324
Collaborator
Merck Sharp & Dohme LLC (Industry)
298
Enrollment
22
Locations
9
Arms
80.5
Actual Duration (Months)
13.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

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).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
298 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 29, 2015
Actual Primary Completion Date :
Aug 31, 2018
Actual Study Completion Date :
Apr 12, 2022

Arms and Interventions

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: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•
    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: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•
    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: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•
    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: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•
    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: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•
    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: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•
    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: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•
    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: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•
    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: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Pembrolizumab
    Administered IV
    Other Names:
  • MK3475

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [Baseline to Measured Progressive Disease (Estimated up to 24 Months)]

    Secondary Outcome Measures

    1. Proportion of Participants Who Achieve Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] [Baseline to Measured Progressive Disease (Estimated up 24 Months)]

    2. Proportion of Participants who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)] [Baseline to Measured Progressive Disease (Estimated up 24 Months)]

    3. Duration of Response (DoR) [Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up 24 Months)]

    4. Time to First Response (TTR) [Baseline to Date of CR or PR (Estimated up 24 Months)]

    5. Progression Free Survival (PFS) [Baseline to Progressive Disease or Death of Any Cause (Estimated up 24 Months)]

    6. Overall Survival (OS) [Baseline to Death from Any Cause (Estimated up 24 Months)]

    7. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab [Predose Day 1 Cycle 1 through Cycle 9 Day 1 (21 Day Cycles)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Yale University School of Medicine New Haven Connecticut United States 06520-8020
    2 Florida Cancer Specialists Fort Myers Florida United States 33916
    3 Florida Cancer Specialists and Research Institute Saint Petersburg Florida United States 33705
    4 Tennessee Oncology PLLC Chattanooga Tennessee United States 37404
    5 Sarah Cannon Research Institute SCRI Nashville Tennessee United States 37203
    6 Tennessee Oncology PLLC Nashville Tennessee United States 37203
    7 Seattle Cancer Care Alliance Seattle Washington United States 98109
    8 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 Cedex France 21034
    9 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
    10 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
    11 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
    12 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 01307
    13 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
    14 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
    15 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-Shi Japan 780-0051
    16 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
    17 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 08035
    18 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
    19 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
    20 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 W1G 6AD
    21 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
    22 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

    Sponsors and Collaborators

    • Eli Lilly and Company
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: 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), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02443324
    Other Study ID Numbers:
    • 15787
    • I4T-MC-JVDF
    • 2015-001473-40
    • KEYNOTE -098
    First Posted:
    May 13, 2015
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Keywords provided by Eli Lilly and Company
    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
    Additional relevant MeSH terms:
    Carcinoma
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Adenocarcinoma
    Biliary Tract Neoplasms
    Carcinoma, Transitional Cell
    Pembrolizumab
    Ramucirumab

    Study Results

    No Results Posted as of Aug 18, 2022