This is a multi-center, single-arm, open-label, Phase 2 clinical study of Dacomitinib for EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases.
Name: Dacomitinib
Description: Progression Free Survival (PFS)is defined as the time from start of treatment to the date of disease progression as defined by RECIST v1.1 per investigator review or death due to any cause, whichever occurred first.
Measure: Progression Free Survival (PFS) Time: 20 monthsDescription: Intracranial Objective Response Rate is defined as the proportion of subjects with a BOR of either CR or PR of intracranial disease, where BOR is the best response recorded from the start of treatment until disease progression or start of other anticancer therapy. As per RECIST v1.1 guidelines, PR and CR do not need to be confirmed following initial response documentation.
Measure: Intracranial Objective Response Rate Time: 20 monthsDescription: Objective Response Rate is defined as the proportion of subjects with a BOR of either CR or PR, where BOR is the best response recorded from the start of treatment until disease progression or start of other anticancer therapy. As per RECIST v1.1 guidelines, PR and CR do not need to be confirmed following initial response documentation.
Measure: Objective Response Rate Time: 20 monthsDescription: Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria.
Measure: Disease control rate Time: 20 monthsDescription: Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria
Measure: Duration of response Time: 20 monthsDescription: Intracranial Progression Free Survival is defined as confirmed by investigator with morphologically proven intracranial PD [presence of at least one key symptom in combination with radiologic evidence including CT or MRI of PD in the brain on follow-up or death due to any cause, whichever occurred first.
Measure: Intracranial Progression Free Survival Time: 20 monthsDescription: Overall Survival is defined as the time from start of treatment to the date of death for any cause. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive.
Measure: Overall Survival Time: 48 monthsAllocation: N/A
Single Group Assignment
There are 2 SNPs
In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive.. Inclusion Criteria: - Provision of a voluntarily given, personally signed and dated, written informed consent document; - Age≥18 years, male or female; - The presence of an EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) in tumor specimen determined by the local laboratory. --- L858R ---
It is acceptable for subjects with the presence of the exon 20 T790M mutation together with either EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) to be included in this study; - Evidence of newly diagnosed stage IIIB/IV (based on Union for International Cancer Control (UICC) staging system version 7) or recurrent (minimum of 12 months disease free interval between completion of systemic therapy and recurrence of NSCLC required) NSCLC of adenocarcinoma histo- and/or cytopathology or its pathologically accepted variants using tumor specimen (assessed according to accepted standards by a local laboratory). --- T790M --- --- L858R ---
Variations of adenocarcinoma are allowed, however no squamous element can be present; - Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation. --- L858R ---
Both mutations (exon 19 deletion and L858R mutation in exon 21) within a tumor sample; - Symptomatic brain or leptomeningeal metastases, who are neurologically unstable or require increasing doses of steroids to manage CNS symptoms within two weeks prior to starting dacomitinib; - Any previous anti-cancer systemic treatment of locally advanced, or metastatic NSCLC including but not limited to chemotherapy, targeted therapies, small molecules, EGFR-TKIs and other TKIs, monoclonal antibodies, anti-cancer vaccines, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, i.e., non-target lesions). --- L858R ---
Inclusion Criteria: - Provision of a voluntarily given, personally signed and dated, written informed consent document; - Age≥18 years, male or female; - The presence of an EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) in tumor specimen determined by the local laboratory. --- L858R ---
It is acceptable for subjects with the presence of the exon 20 T790M mutation together with either EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) to be included in this study; - Evidence of newly diagnosed stage IIIB/IV (based on Union for International Cancer Control (UICC) staging system version 7) or recurrent (minimum of 12 months disease free interval between completion of systemic therapy and recurrence of NSCLC required) NSCLC of adenocarcinoma histo- and/or cytopathology or its pathologically accepted variants using tumor specimen (assessed according to accepted standards by a local laboratory). --- T790M ---
Variations of adenocarcinoma are allowed, however no squamous element can be present; - Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation. --- L858R --- --- T790M ---