Back to resultsA Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer (D4190C00006)
Primary Purpose
NSCLC, Non-small Cell Lung Cancer, Lung Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MEDI4736
Tremelimumab
tremelimumab
Sponsored by
About this trial
This is an interventional treatment trial for NSCLC focused on measuring anti-CTLA-4, anti-PD-L1, immunotherapy, IMTC
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Advanced non-small cell lung cancer
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate organ and marrow function
Exclusion Criteria:
- Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
- Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs
- Active or prior documented autoimmune disease within the last 2 years.
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Dose Escalation
Arm A
Arm B
Arm C
Arm Description
MEDI4736 and tremelimumab received by intravenous infusion.
Medi4736 and tremelimumab received by intravenous infusion
MEDI4736 and tremelimumab received by intravenous infusion
MEDI4736 and tremelimumab received by intravenous infursion
Outcomes
Primary Outcome Measures
Number of subjects reporting adverse events
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
Objective response
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.
Number of subjects experiencing dose-limiting toxicities (DLTs)
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
Immunogenicity of tremelimumab in combination with MEDI4736
Immunogenicity of MEDI4736 and tremelimumab will include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Antitumor activity of tremelimumab in combination with MEDI4736
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).
Pharmacokinetic parameters
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).
Number of subjects reporting adverse events
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02000947
Brief Title
A Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer
Acronym
D4190C00006
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
October 25, 2013 (Actual)
Primary Completion Date
September 17, 2019 (Actual)
Study Completion Date
September 17, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NSCLC, Non-small Cell Lung Cancer, Lung Cancer
Keywords
anti-CTLA-4, anti-PD-L1, immunotherapy, IMTC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
459 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
MEDI4736 and tremelimumab received by intravenous infusion.
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Medi4736 and tremelimumab received by intravenous infusion
Arm Title
Arm B
Arm Type
Experimental
Arm Description
MEDI4736 and tremelimumab received by intravenous infusion
Arm Title
Arm C
Arm Type
Experimental
Arm Description
MEDI4736 and tremelimumab received by intravenous infursion
Intervention Type
Drug
Intervention Name(s)
MEDI4736
Intervention Description
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).
Intervention Type
Drug
Intervention Name(s)
Tremelimumab
Intervention Description
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
Intervention Type
Drug
Intervention Name(s)
tremelimumab
Intervention Description
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
Primary Outcome Measure Information:
Title
Number of subjects reporting adverse events
Description
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
Time Frame
Screening through 90 days after the last dose of study medication
Title
Objective response
Description
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.
Time Frame
At least 24 weeks as compared to baseline
Title
Number of subjects experiencing dose-limiting toxicities (DLTs)
Description
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.
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
Secondary Outcome Measure Information:
Title
Immunogenicity of tremelimumab in combination with MEDI4736
Description
Immunogenicity of MEDI4736 and tremelimumab will include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Time Frame
During treatment through study completion, about 2 years
Title
Antitumor activity of tremelimumab in combination with MEDI4736
Description
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).
Time Frame
During treatment through study completion, about 2 years
Title
Pharmacokinetic parameters
Description
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).
Time Frame
During treatment through study completion, about 2 years
Title
Number of subjects reporting adverse events
Description
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
Time Frame
Screening through 90 days after the last dose of study medication
Other Pre-specified Outcome Measures:
Title
Biomarkers
Description
To evaluate biomarkers that may correlate with clinical activity of MEDI4736 in combination with tremelimumab
Time Frame
During treatment through study completion, about 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
101 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years
Advanced non-small cell lung cancer
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Adequate organ and marrow function
Exclusion Criteria:
Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs
Active or prior documented autoimmune disease within the last 2 years.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MedImmune LLC
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
Research Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Research Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Research Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Research Site
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Research Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Research Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77521
Country
United States
Facility Name
Research Site
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Research Site
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Research Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Research Site
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Research Site
City
Darlinghurst
ZIP/Postal Code
2010
Country
Australia
Facility Name
Research Site
City
Gosford
ZIP/Postal Code
2250
Country
Australia
Facility Name
Research Site
City
Kogarah
ZIP/Postal Code
2217
Country
Australia
Facility Name
Research Site
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Research Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Research Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Research Site
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
Facility Name
Research Site
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Research Site
City
La Tronche
ZIP/Postal Code
38043
Country
France
Facility Name
Research Site
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Research Site
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Research Site
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Research Site
City
Montpellier Cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Research Site
City
Saint Herblain
ZIP/Postal Code
44805
Country
France
Facility Name
Research Site
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20141
Country
Italy
Facility Name
Research Site
City
Rozzano
ZIP/Postal Code
20089
Country
Italy
Facility Name
Research Site
City
Saronno
ZIP/Postal Code
21047
Country
Italy
Facility Name
Research Site
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
Research Site
City
Sondrio
ZIP/Postal Code
23100
Country
Italy
Facility Name
Research Site
City
Cheongju-si
ZIP/Postal Code
28644
Country
Korea, Republic of
Facility Name
Research Site
City
Incheon
ZIP/Postal Code
405-760
Country
Korea, Republic of
Facility Name
Research Site
City
Seongnam-si
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
05368
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08028
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Research Site
City
Jaen
ZIP/Postal Code
23007
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Research Site
City
Malaga
ZIP/Postal Code
29730
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Research Site
City
Valencia
ZIP/Postal Code
46015
Country
Spain
Facility Name
Research Site
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Research Site
City
London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
Facility Name
Research Site
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
26858122
Citation
Antonia S, Goldberg SB, Balmanoukian A, Chaft JE, Sanborn RE, Gupta A, Narwal R, Steele K, Gu Y, Karakunnel JJ, Rizvi NA. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016 Mar;17(3):299-308. doi: 10.1016/S1470-2045(15)00544-6. Epub 2016 Feb 6.
Results Reference
derived
Learn more about this trial
A Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer
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