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

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: Completed
• Conditions: NSCLC; Lung Cancer; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: MEDI4736; Drug: Tremelimumab; Drug: tremelimumab

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: Interventional
• Enrollment (Actual): 459
• Phase: Phase 1

Contacts and Locations

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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	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

• Sponsor: MedImmune LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2013
• Primary Completion (Actual): September 17, 2019
• Study Completion (Actual): September 17, 2019

Study Registration Dates

• First Submitted: November 27, 2013
• First Submitted That Met QC Criteria: November 27, 2013
• First Posted (Estimate): December 4, 2013

Study Record Updates

• Last Update Posted (Actual): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: immunotherapy; anti-PD-L1; anti-CTLA-4; IMTC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab; Antibodies, Monoclonal
• Other Study ID 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