Clincosm LogoSign in Get a demo

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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02572687
Collaborator
AstraZeneca (Industry)
85
Enrollment
28
Locations
3
Arms
58.8
Actual Duration (Months)
3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
85 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 MEDI4736 in Patients With Locally Advanced and Unresectable or Metastatic Gastrointestinal or Thoracic Malignancies
Actual Study Start Date :
Feb 19, 2016
Actual Primary Completion Date :
Mar 27, 2018
Actual Study Completion Date :
Jan 13, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ramucirumab + MEDI4736 (NSCLC)

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.

Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-11121B
  • Cyramza

    • Drug: MEDI4736
    Administered IV
    Experimental: Ramucirumab + MEDI4736 (Gastric/GEJ)

    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.

    Drug: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-11121B
  • Cyramza

    • Drug: MEDI4736
    Administered IV
    Experimental: Ramucirumab + MEDI4736 (HCC)

    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.

    Drug: Ramucirumab
    Administered IV
    Other Names:
  • LY3009806
  • IMC-11121B
  • Cyramza

    • Drug: MEDI4736
    Administered IV

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants with Dose Limiting Toxicities (DLTs) [Cycle 1 (up to 28 days)]

    Secondary Outcome Measures

    1. Percentage of Participants with a Best Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) [Baseline to Disease Progression (Approximately 22 Months)]

    2. Proportion of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) [Baseline to Disease Progression (Approximately 22 Months)]

    3. Duration of Response (DoR) [Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 22 Months)]

    4. Time to First Response (TTR) [Baseline to Date of CR or PR (Approximately 22 Months)]

    5. Progression Free Survival (PFS) [Baseline to Progressive Disease or Death from Any Cause (Approximately 22 Months)]

    6. Overall Survival (OS) [Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months)]

    7. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab and MEDI4736 [Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)]

    8. PK: Minimum Concentration (Cmin) of Ramucirumab and MEDI4736 [Predose Cycle 1 Day 1 through Follow up (Approximately 22 Months)]

    9. Number of Participants with Treatment Emergent Anti Ramucirumab Antibodies [Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)]

    10. Number of Participants with Treatment Emergent Anti MEDI4736 Antibodies [Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months)]

    Eligibility Criteria

    Criteria

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCLA Medical Center Santa Monica California United States 90404
    2 Johns Hopkins University Baltimore Maryland United States 21231
    3 Washington University Medical Center Saint Louis Missouri United States 63110
    4 Carolinas Medical Center Charlotte North Carolina United States 28204
    5 The Miriam Hospital Providence Rhode Island United States 02906
    6 Vanderbilt University Medical Center Nashville Tennessee United States 37232-6307
    7 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    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. Besancon Cedex France 25030
    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. Marseille Cedex 5 France 13385
    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. Montpellier Cedex 5 France 34298
    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. Saint Etienne Cedex 2 France 42055
    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. Großhansdorf Germany 22927
    13 Hadassah Medical Center - Ein Karem Jerusalem Israel 9112001
    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. Ramat Gan Israel 5266202
    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. Tel Aviv Israel 6423906
    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. Milano Italy 20133
    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. Rozzano Italy 20089
    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 Seoul Korea, Republic of 03080
    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 Seoul Korea, Republic of 03722
    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 Seoul Korea, Republic of 05505
    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. Seoul Korea, Republic of 06351
    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. Madrid Spain 28040
    23 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. Malaga Spain 29010
    24 Hospital Virgen del Rocío Sevilla Spain 41013
    25 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. Tainan Taiwan 70403
    26 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. Tainan Taiwan 704
    27 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 Tainan Taiwan 73657
    28 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. Taipei Taiwan 10048

    Sponsors and Collaborators

    • Eli Lilly and Company
    • AstraZeneca

    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:
    NCT02572687
    Other Study ID Numbers:
    • 16116
    • I4T-MC-JVDJ
    • 2015-003013-14
    First Posted:
    Oct 9, 2015
    Last Update Posted:
    Jan 20, 2021
    Last Verified:
    Jan 1, 2021
    Keywords provided by Eli Lilly and Company
    metastatic
    advanced
    immuno-oncology
    vascular endothelial growth factor (VEGF)
    angiogenesis
    PD-1
    PD-L1
    Additional relevant MeSH terms:
    Adenocarcinoma
    Carcinoma, Hepatocellular
    Durvalumab
    Ramucirumab

    Study Results

    No Results Posted as of Jan 20, 2021