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

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ClinicalTrials.gov Identifier: NCT02000947
Recruitment Status : Active, not recruiting
First Posted : December 4, 2013
Last Update Posted : April 12, 2018
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

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 Phase 2

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  (Clinical Trial)
Actual Enrollment : 459 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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 : October 25, 2013
Estimated Primary Completion Date : November 21, 2018
Estimated Study Completion Date : November 21, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Durvalumab
U.S. FDA Resources

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).



Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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).

  4. 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


Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02000947


  Show 69 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: MedImmune LLC MedImmune LLC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02000947     History of Changes
Other Study ID Numbers: D4190C00006
2015-003715-38 ( EudraCT Number )
First Posted: December 4, 2013    Key Record Dates
Last Update Posted: April 12, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MedImmune LLC:
anti-CTLA-4
anti-PD-L1
immunotherapy
IMTC

Additional relevant MeSH terms:
Tremelimumab
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents