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

October 29, 2019 updated by: MedImmune LLC

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
459

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Darlinghurst, Australia, 2010
        • Research Site
      • Gosford, Australia, 2250
        • Research Site
      • Kogarah, Australia, 2217
        • Research Site
  • Belgium
      • Bruxelles, Belgium, 1000
        • Research Site
      • Gent, Belgium, 9000
        • Research Site
      • Liege, Belgium, 4000
        • Research Site
  • France
      • 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
        • Research Site
  • Italy
      • 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
        • Research Site
  • Korea, Republic of
      • 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, 03080
        • Research Site
      • Seoul, Korea, Republic of, 02841
        • Research Site
      • Seoul, Korea, Republic of, 06351
        • Research Site
      • Seoul, Korea, Republic of, 120-752
        • Research Site
      • Seoul, Korea, Republic of, 138-736
        • Research Site
      • Seoul, Korea, Republic of, 05368
        • Research Site
  • Spain
      • Barcelona, Spain, 08035
        • Research Site
      • Barcelona, Spain, 08028
        • 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
        • Research Site
  • Taiwan
      • Tainan, Taiwan, 704
        • Research Site
      • Taipei, Taiwan, 10048
        • Research Site
  • United Kingdom
      • London, United Kingdom, W1G 6AD
        • Research Site
      • Manchester, United Kingdom, M20 4BX
        • Research Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-3300
        • Research Site
    • Arizona
      • Tucson, Arizona, United States, 85715
        • Research Site
    • California
      • Los Angeles, California, United States, 90025
        • Research Site
      • Los Angeles, California, United States, 90095
        • Research Site
      • San Francisco, California, United States, 94158
        • Research Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Research Site
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Research Site
    • Delaware
      • Newark, Delaware, United States, 19713
        • Research Site
    • Florida
      • Tampa, Florida, United States, 33612
        • Research Site
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Research Site
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Research Site
      • Boston, Massachusetts, United States, 02215
        • Research Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Research Site
      • Detroit, Michigan, United States, 48201
        • Research Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Research Site
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Research Site
    • New York
      • New York, New York, United States, 10032
        • Research Site
      • New York, New York, United States, 10065
        • Research Site
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97213
        • Research Site
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Research Site
      • Houston, Texas, United States, 77521
        • Research Site
      • Tyler, Texas, United States, 75702
        • Research Site
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Research Site
    • Washington
      • Seattle, Washington, United States, 98109
        • Research Site
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 101 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Screening through 90 days after the last dose of study medication
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.
At least 24 weeks as compared to baseline
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.
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Screening through 90 days after the last dose of study medication
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).
During treatment through study completion, about 2 years
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).
During treatment through study completion, about 2 years
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).
During treatment through study completion, about 2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
During treatment through study completion, about 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
MedImmune LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 25, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 17, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 17, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 27, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 27, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 4, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 31, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 29, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D4190C00006
  • 2015-003715-38 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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