Lung Cancer, Non-small Cell Lung Cancer, NSCLC
Conditions
Keywords
anti-CTLA-4, anti-PD-L1, immunotherapy, IMTC
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).
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.
Interventions
DRUGMEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb).
DRUGTremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
DRUGtremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
Sponsors
MedImmune LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 101 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers | During treatment through study completion, about 2 years | To evaluate biomarkers that may correlate with clinical activity of MEDI4736 in combination with tremelimumab |
Countries
Australia, Belgium, France, Italy, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed