The objective of this study is to investigate the safety, tolerability and antitumor activity of novel combination therapies administered in subjects with advanced EGFRm NSCLC
Name: MEDI9447
Name: Osimertinib
Name: AZD4635
Description: The primary endpoint is safety as assessed by the presence of adverse events and serious adverse events
Measure: Incidence of Adverse Events as a measure of safety Time: Screening through 90 days after last dose of investigational productDescription: The primary endpoint in dose expansion phase includes efficacy assessed by objective response
Measure: Objective response rate as a measure of anti tumor activity in dose expansion phase Time: During treatment through study completion, about 2 years after the last subject dosedDescription: The duration from the first documentation of objective response (OR) to the first documented disease progression or death due to any cause, whichever occurs first
Measure: Duration of Response (DoR) Time: During treatment through study completion, about 2 years after the last subject dosedDescription: Defined as complete response (CR), partial response (PR) or stable disease (SD)
Measure: Disease Control (DC) Time: During treatment through study completion, about 2 years after the last subject dosedDescription: From the start of treatment with investigational product until the first documentation of disease progression or death due to any cause, whichever occurs first.
Measure: Progression Free Survival (PFS) Time: During treatment through study completion, about 2 years after the last subject dosedDescription: From the start of treatment with investigational product until death due to any cause
Measure: Overall Survival (OS) Time: During treatment through study completion, about 2 years after the last subject dosedDescription: Defined as best overall response of confirmed CR or confirmed PR according to RECIST version 1.1
Measure: Objective Response by T790M status Time: During treatment through study completion, about 2 years after the last subject dosedDescription: Defined as CR, PR or SD
Measure: Disease Control by T790M status Time: During treatment through study completion, about 2 years after the last subject dosedDescription: Pharmacokinetic
Measure: Serum MEDI9447 concentration levels Time: During treatment through 90 days after last dose of investigational productDescription: Pharmacokinetic
Measure: Serum Osimertinib concentration levels Time: During treatment through 90 days after last dose of investigational productDescription: Pharmacokinetic
Measure: Serum AZD4635 concentration levels Time: During treatment through 90 days after last dose of investigational productDescription: Immunogenicity
Measure: Development of detectable anti-drug antibody(ADA) to MEDI9447 Time: During treatment through 90 days after last dose of investigational productAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Objective Response by T790M status. --- T790M ---
Disease Control by T790M status. --- T790M ---
Inclusion Criteria: 1. Age ≥ 18 2. ECOG Performance Status of 0 or 1 3. Weight ≥ 35 kg 4. Diagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFR mutation - For Arm A: must have received 1 prior line of therapy with an EGFR TKI and confirmed T790M negative - For Arm B: must have received at least 2 but not more than 4 prior lines of therapy. --- T790M ---
Additional Exclusion Criteria for Arm B 1. Herbal preparations/medications are not allowed throughout the study 2. History of seizures excluding those that occurred due to previously untreated CNS metastasis Inclusion Criteria: 1. Age ≥ 18 2. ECOG Performance Status of 0 or 1 3. Weight ≥ 35 kg 4. Diagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFR mutation - For Arm A: must have received 1 prior line of therapy with an EGFR TKI and confirmed T790M negative - For Arm B: must have received at least 2 but not more than 4 prior lines of therapy. --- T790M ---