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

Sponsor

MedImmune LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT02000947

Collaborator

(none)

459

Enrollment

Locations

Arms

70.7

Actual Duration (Months)

6.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

459 participants

Allocation:

N/A

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 :

Oct 25, 2013

Actual Primary Completion Date :

Sep 17, 2019

Actual Study Completion Date :

Sep 17, 2019

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

Number of subjects reporting adverse events [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
Objective response [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.
Number of subjects experiencing dose-limiting toxicities (DLTs) [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

Immunogenicity of tremelimumab in combination with MEDI4736 [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).
Antitumor activity of tremelimumab in combination with MEDI4736 [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).
Pharmacokinetic parameters [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).
Number of subjects reporting adverse events [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

Biomarkers [During treatment through study completion, about 2 years]
To evaluate biomarkers that may correlate with clinical activity of MEDI4736 in combination with tremelimumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 101 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35294-3300
2	Research Site	Tucson	Arizona	United States	85715
3	Research Site	Los Angeles	California	United States	90025
4	Research Site	Los Angeles	California	United States	90095
5	Research Site	San Francisco	California	United States	94158
6	Research Site	Aurora	Colorado	United States	80045
7	Research Site	New Haven	Connecticut	United States	06510
8	Research Site	Newark	Delaware	United States	19713
9	Research Site	Tampa	Florida	United States	33612
10	Research Site	Indianapolis	Indiana	United States	46202
11	Research Site	Baltimore	Maryland	United States	21287
12	Research Site	Boston	Massachusetts	United States	02114
13	Research Site	Boston	Massachusetts	United States	02215
14	Research Site	Ann Arbor	Michigan	United States	48109
15	Research Site	Detroit	Michigan	United States	48201
16	Research Site	Saint Louis	Missouri	United States	63110
17	Research Site	Lebanon	New Hampshire	United States	03756
18	Research Site	New York	New York	United States	10032
19	Research Site	New York	New York	United States	10065
20	Research Site	Huntersville	North Carolina	United States	28078
21	Research Site	Columbus	Ohio	United States	43210
22	Research Site	Portland	Oregon	United States	97213
23	Research Site	Fort Worth	Texas	United States	76104
24	Research Site	Houston	Texas	United States	77521
25	Research Site	Tyler	Texas	United States	75702
26	Research Site	Fairfax	Virginia	United States	22031
27	Research Site	Seattle	Washington	United States	98109
28	Research Site	Morgantown	West Virginia	United States	26506
29	Research Site	Darlinghurst		Australia	2010
30	Research Site	Gosford		Australia	2250
31	Research Site	Kogarah		Australia	2217
32	Research Site	Bruxelles		Belgium	1000
33	Research Site	Gent		Belgium	9000
34	Research Site	Liege		Belgium	4000
35	Research Site	Bordeaux Cedex		France	33076
36	Research Site	Dijon		France	21079
37	Research Site	La Tronche		France	38043
38	Research Site	Lille		France	59000
39	Research Site	Lyon		France	69008
40	Research Site	Marseille		France	13385
41	Research Site	Montpellier Cedex 5		France	34298
42	Research Site	Saint Herblain		France	44805
43	Research Site	Bologna		Italy	40138
44	Research Site	Milano		Italy	20141
45	Research Site	Rozzano		Italy	20089
46	Research Site	Saronno		Italy	21047
47	Research Site	Siena		Italy	53100
48	Research Site	Sondrio		Italy	23100
49	Research Site	Cheongju-si		Korea, Republic of	28644
50	Research Site	Incheon		Korea, Republic of	405-760
51	Research Site	Seongnam-si		Korea, Republic of	13620
52	Research Site	Seoul		Korea, Republic of	02841
53	Research Site	Seoul		Korea, Republic of	03080
54	Research Site	Seoul		Korea, Republic of	05368
55	Research Site	Seoul		Korea, Republic of	06351
56	Research Site	Seoul		Korea, Republic of	120-752
57	Research Site	Seoul		Korea, Republic of	138-736
58	Research Site	Barcelona		Spain	08028
59	Research Site	Barcelona		Spain	08035
60	Research Site	Jaen		Spain	23007
61	Research Site	Madrid		Spain	28034
62	Research Site	Madrid		Spain	28041
63	Research Site	Malaga		Spain	29730
64	Research Site	Sevilla		Spain	41013
65	Research Site	Valencia		Spain	46015
66	Research Site	Tainan		Taiwan	704
67	Research Site	Taipei		Taiwan	10048
68	Research Site	London		United Kingdom	W1G 6AD
69	Research Site	Manchester		United Kingdom	M20 4BX