This is a single arm open-label multi-center phase II study, investigating disease control rate after 3 months of treatment with trastuzumab-emtansine/osimertinib combination therapy in patients with advanced EGFR mutation positive non-small cell lung cancer (NSCLC) with HER2 bypass track resistance.
Name: Trastuzumab emtansine
Description: Safety as indicated by intensity and incidence of adverse events, graded according to NCI CTCAE Version 4.03Measure: Safety (intensity and incidence of adverse events) Time: Up to 30 days after last study drug intake
Description: Complete response and partial response after 3 months of treatmentMeasure: Objective response rate according to RECIST v1.1 after 3 months of treatment Time: From date of registration until 3 months.
Description: PFS, defined as the time from first administration of the study drug combination to disease progression by RECIST v1.1. or lost to follow up or death, whichever comes firstMeasure: Progression-free survival Time: From date of registration until the date of first documented progression up to 100 months
Description: DCR, defined as the percentage of patients with stable disease (SD), partial response (PR) or complete response (CR)Measure: Disease control rate, after 3 months of treatment Time: From date of registration until 3 months.
Description: OS, defined as the time from first administration of the study drug combination to lost to follow up or death, whichever comes firstMeasure: Overall survival Time: From date of registration until the date of death from any cause, assessed up to 100 months.
Description: cfDNA samples will be collected to assess predictors of response and resistanceMeasure: Genetic profiling to assess predictors of response and resistance - circulating free (cf)DNA Time: At baseline, every 6 weeks and at treatment discontinuation (expected 6 months after start)
Single Group Assignment
There is one SNP
3. A rebiopsy after having acquired resistance to a first, second or third generation TKI-treatment must have been performed and be: 1. Negative for T790M in case of treatment with a first or second generation EGFR TKI. --- T790M ---
After progression on a third generation EGFR TKI patients may either be positive or negative for T790M. --- T790M ---