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A Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer (D4190C00006)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02000947
Recruitment Status : Completed
First Posted : December 4, 2013
Last Update Posted : October 31, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
The purpose of this study is to determine if MEDI4736 will be adequately tolerated in combination with tremelimumab in subjects with advanced non-small cell lung cancer (NSCLC).

Condition or disease Intervention/treatment Phase
NSCLC Non-small Cell Lung Cancer Lung Cancer Drug: MEDI4736 Drug: Tremelimumab Drug: tremelimumab Phase 1

Detailed Description:
This is a multicenter, open-label, dose-escalation, and dose expansion study of MEDI4736 in combination with tremelimumab to evaluate the safety, tolerability, pharmacokinetic (PK), immunogenicity, and antitumor activity of MEDI4736 in combination with tremelimumab in adult subjects with advanced NSCLC.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 459 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer
Actual Study Start Date : October 25, 2013
Actual Primary Completion Date : September 17, 2019
Actual Study Completion Date : September 17, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Dose Escalation
MEDI4736 and tremelimumab received by intravenous infusion.
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).

Drug: Tremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).

Experimental: Arm A
Medi4736 and tremelimumab received by intravenous infusion
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).

Drug: Tremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).

Experimental: Arm B
MEDI4736 and tremelimumab received by intravenous infusion
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).

Drug: tremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).

Experimental: Arm C
MEDI4736 and tremelimumab received by intravenous infursion
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).

Drug: tremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).




Primary Outcome Measures :
  1. Number of subjects reporting adverse events [ Time Frame: Screening through 90 days after the last dose of study medication ]
    The number of subjects reporting adverse events (AEs) and number (percentage) of subjects reporting serious adverse events (SAEs) as graded by CTCAE Version 4.03

  2. Objective response [ Time Frame: At least 24 weeks as compared to baseline ]
    Best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as defined as the best response among all overall responses recorded from the start of treatment until progression, or the last evaluable disease assessment in the absence of progressive disease (PD) prior to the initiation of subsequent anti-cancer therapy, or discontinuation from the study, whichever occurs first.

  3. Number of subjects experiencing dose-limiting toxicities (DLTs) [ Time Frame: Depending upon the cohort, the DLT evaluation period is from the 1st dose of study medication until (1) the 3rd dose of MEDI4736 and tremelimumab (2) the 2nd dose of MEDI4736 and tremelimumab or (3) the 3rd dose of MEDI4736 and 2nd dose of tremelimumab ]
    The maximum tolerated dose (MTD), which is the highest dose within a cohort where no more than 1 out of 6 subjects experience DLTs or the highest protocol-defined dose for each agent in the absence of exceeding the MTD, will be evaluated using the following safety assessments: adverse events, serious advents, laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results. Measurements will be aggregated to determine whether a subject has experienced a DLT as assessed by the investigator.


Secondary Outcome Measures :
  1. Immunogenicity of tremelimumab in combination with MEDI4736 [ Time Frame: During treatment through study completion, about 2 years ]
    Immunogenicity of MEDI4736 and tremelimumab will include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).

  2. Antitumor activity of tremelimumab in combination with MEDI4736 [ Time Frame: During treatment through study completion, about 2 years ]
    Antitumor activity will include objective response (OR) and disease control (DC) based on RECIST Version 1.1, duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

  3. Pharmacokinetic parameters [ Time Frame: During treatment through study completion, about 2 years ]
    Assessment of PK of MEDI4736 and tremelimumab will include individual MEDI4736 and tremelimumab concentrations in serum, and PK parameters including peak concentration (Cmax), area under the concentration-time curve (AUC), clearance (CL), and half-life (t½).

  4. Number of subjects reporting adverse events [ Time Frame: Screening through 90 days after the last dose of study medication ]
    The number of subjects reporting adverse events (AEs) and number (percentage) of subjects reporting serious adverse events (SAEs) as graded by CTCAE Version 4.03


Other Outcome Measures:
  1. Biomarkers [ Time Frame: During treatment through study completion, about 2 years ]
    To evaluate biomarkers that may correlate with clinical activity of MEDI4736 in combination with tremelimumab



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 101 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Advanced non-small cell lung cancer
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  4. Adequate organ and marrow function

Exclusion Criteria:

  1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
  2. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs
  3. Active or prior documented autoimmune disease within the last 2 years.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02000947


Locations
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United States, Alabama
Research Site
Birmingham, Alabama, United States, 35294-3300
United States, Arizona
Research Site
Tucson, Arizona, United States, 85715
United States, California
Research Site
Los Angeles, California, United States, 90025
Research Site
Los Angeles, California, United States, 90095
Research Site
San Francisco, California, United States, 94158
United States, Colorado
Research Site
Aurora, Colorado, United States, 80045
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06510
United States, Delaware
Research Site
Newark, Delaware, United States, 19713
United States, Florida
Research Site
Tampa, Florida, United States, 33612
United States, Indiana
Research Site
Indianapolis, Indiana, United States, 46202
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02114
Research Site
Boston, Massachusetts, United States, 02215
United States, Michigan
Research Site
Ann Arbor, Michigan, United States, 48109
Research Site
Detroit, Michigan, United States, 48201
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63110
United States, New Hampshire
Research Site
Lebanon, New Hampshire, United States, 03756
United States, New York
Research Site
New York, New York, United States, 10032
Research Site
New York, New York, United States, 10065
United States, North Carolina
Research Site
Huntersville, North Carolina, United States, 28078
United States, Ohio
Research Site
Columbus, Ohio, United States, 43210
United States, Oregon
Research Site
Portland, Oregon, United States, 97213
United States, Texas
Research Site
Fort Worth, Texas, United States, 76104
Research Site
Houston, Texas, United States, 77521
Research Site
Tyler, Texas, United States, 75702
United States, Virginia
Research Site
Fairfax, Virginia, United States, 22031
United States, Washington
Research Site
Seattle, Washington, United States, 98109
United States, West Virginia
Research Site
Morgantown, West Virginia, United States, 26506
Australia
Research Site
Darlinghurst, Australia, 2010
Research Site
Gosford, Australia, 2250
Research Site
Kogarah, Australia, 2217
Belgium
Research Site
Bruxelles, Belgium, 1000
Research Site
Gent, Belgium, 9000
Research Site
Liege, Belgium, 4000
France
Research Site
Bordeaux Cedex, France, 33076
Research Site
Dijon, France, 21079
Research Site
La Tronche, France, 38043
Research Site
Lille, France, 59000
Research Site
Lyon, France, 69008
Research Site
Marseille, France, 13385
Research Site
Montpellier Cedex 5, France, 34298
Research Site
Saint Herblain, France, 44805
Italy
Research Site
Bologna, Italy, 40138
Research Site
Milano, Italy, 20141
Research Site
Rozzano, Italy, 20089
Research Site
Saronno, Italy, 21047
Research Site
Siena, Italy, 53100
Research Site
Sondrio, Italy, 23100
Korea, Republic of
Research Site
Cheongju-si, Korea, Republic of, 28644
Research Site
Incheon, Korea, Republic of, 405-760
Research Site
Seongnam-si, Korea, Republic of, 13620
Research Site
Seoul, Korea, Republic of, 02841
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 05368
Research Site
Seoul, Korea, Republic of, 06351
Research Site
Seoul, Korea, Republic of, 120-752
Research Site
Seoul, Korea, Republic of, 138-736
Spain
Research Site
Barcelona, Spain, 08028
Research Site
Barcelona, Spain, 08035
Research Site
Jaen, Spain, 23007
Research Site
Madrid, Spain, 28034
Research Site
Madrid, Spain, 28041
Research Site
Malaga, Spain, 29730
Research Site
Sevilla, Spain, 41013
Research Site
Valencia, Spain, 46015
Taiwan
Research Site
Tainan, Taiwan, 704
Research Site
Taipei, Taiwan, 10048
United Kingdom
Research Site
London, United Kingdom, W1G 6AD
Research Site
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
MedImmune LLC
Investigators
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Study Director: MedImmune LLC MedImmune LLC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02000947    
Other Study ID Numbers: D4190C00006
2015-003715-38 ( EudraCT Number )
First Posted: December 4, 2013    Key Record Dates
Last Update Posted: October 31, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
anti-CTLA-4
anti-PD-L1
immunotherapy
IMTC
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs