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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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NSCLC, Non-small Cell Lung Cancer, Lung Cancer

Intervention / Treatment
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* Drug: MEDI4736
* Drug: Tremelimumab
* Drug: tremelimumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 101 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>MEDI4736 and tremelimumab received by intravenous infusion. | Drug: MEDI4736<br>* MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).<br>Drug: Tremelimumab<br>* Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).<br>|
| Experimental: Arm A<br>Medi4736 and tremelimumab received by intravenous infusion | Drug: MEDI4736<br>* MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).<br>Drug: Tremelimumab<br>* Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).<br>|
| Experimental: Arm B<br>MEDI4736 and tremelimumab received by intravenous infusion | Drug: MEDI4736<br>* MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).<br>Drug: tremelimumab<br>* Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).<br>|
| Experimental: Arm C<br>MEDI4736 and tremelimumab received by intravenous infursion | Drug: MEDI4736<br>* MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).<br>Drug: tremelimumab<br>* Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-CTLA-4, anti-PD-L1, immunotherapy, IMTC