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

Lung Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02000947
• Other study ID #: D4190C00006
• Secondary ID: 2015-003715-38
• Status: Completed
• Phase: Phase 1
• Start date: October 25, 2013
• Est. completion date: September 17, 2019

Study information

• Verified date: October 2019
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 459
• Est. completion date: September 17, 2019
• Est. primary completion date: September 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non-small Cell Lung Cancer
• NSCLC

Intervention

Drug:
• MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).
• Tremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
• tremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).

Locations

Country	Name	City	State
Australia	Research Site	Darlinghurst
Australia	Research Site	Gosford
Australia	Research Site	Kogarah
Belgium	Research Site	Bruxelles
Belgium	Research Site	Gent
Belgium	Research Site	Liege
France	Research Site	Bordeaux Cedex
France	Research Site	Dijon
France	Research Site	La Tronche
France	Research Site	Lille
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Montpellier Cedex 5
France	Research Site	Saint Herblain
Italy	Research Site	Bologna
Italy	Research Site	Milano
Italy	Research Site	Rozzano
Italy	Research Site	Saronno
Italy	Research Site	Siena
Italy	Research Site	Sondrio
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Jaen
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Aurora	Colorado
United States	Research Site	Baltimore	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Columbus	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Worth	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntersville	North Carolina
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Morgantown	West Virginia
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Newark	Delaware
United States	Research Site	Portland	Oregon
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Francisco	California
United States	Research Site	Seattle	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Tucson	Arizona
United States	Research Site	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Italy,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarkers	To evaluate biomarkers that may correlate with clinical activity of MEDI4736 in combination with tremelimumab	During treatment through study completion, about 2 years
Primary	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	Screening through 90 days after the last dose of study medication
Primary	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.	At least 24 weeks as compared to baseline
Primary	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.	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	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).	During treatment through study completion, about 2 years
Secondary	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).	During treatment through study completion, about 2 years
Secondary	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).	During treatment through study completion, about 2 years
Secondary	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	Screening through 90 days after the last dose of study medication