Phase II trial to evaluate trametinib in patients with locally advanced non-squamous, non-small cell lung cancer (NSCLC) whose tumors harbor a non-synonymous NF-1 mutation, with progressive disease on at least one prior line of therapy.
Name: Trametinib
Description: Trametinib 2mg, once daily, PO, 28-day cyclesType: DrugTrametinib 2.0mg PO daily
Description: For participants receiving at least one dose of study treatment, the ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence as assessed over a 1-year period from the start of treatment. The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined. We will test the hypothesis that the ORR is greater than the null hypothesis of 10% using the Fisher's exact test.
Measure: Objective Response Rate (ORR) Time: Up to 1 yearDescription: The DR for Complete Response (CR) and Partial Response (PR) will be measured from the date that the best response is first recorded until the date that PD is documented. For patients who continue treatment post progression, the date of Disease Progression (PD) documentation will be used for analysis. The DR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).
Measure: Duration of Response (DR) Time: Up to 4 yearsDescription: DCR will be defined as the percentage of patients who have achieved CR, PR, or SD for at least 12 weeks. The DCR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).
Measure: Disease Control Rate (DCR) According to RECIST Version 1.1 Criteria. Time: Up to 4 yearsDescription: PFS will be calculated as 1+ the number of days from the first dose of study drugs to documented radiographic progression or death due to any cause over a period of 1 year. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. The Kaplan-Meier analysis will be used to calculate the median PFS with 95% confidence interval.
Measure: Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria. Time: Up to 1 yearDescription: OS will be calculated as 1+ the number of days from the first dose of study drugs to death due to any cause over a period of 1 year. The Kaplan-Meier analysis will be used to calculate the median OS with 95% confidence interval.
Measure: Overall Survival (OS) Time: Up to 1 yearSingle Group Assignment
There are 7 SNPs
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A ---
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A --- --- S768I --- --- V769L --- --- T790M --- --- L833F ---
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A --- --- S768I --- --- V769L --- --- T790M --- --- L833F --- --- L858R ---
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A --- --- S768I --- --- V769L --- --- T790M --- --- L833F --- --- L858R --- --- L861Q ---
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A --- --- S768I ---
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A --- --- S768I --- --- V769L --- --- T790M ---
Patients whose tumors were found to have an EGFR T790M mutation must also have progressed or been intolerable to treatment with osimertinib. --- T790M ---
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A --- --- S768I --- --- V769L ---