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Report for Clinical Trial NCT03424759

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

An Open Label, Multicenter, Phase II Single-arm Trial of AZD9291 in Non-small Cell Lung Cancer (NSCLC) Patients With Uncommon Epidermal Growth Factor Receptor Mutations

EGFR (ErbB1) mutations define a lung cancer subtype with exquisite sensitivity to EGFR tyrosine kinase inhibitors (TKIs). While in-frame deletion in exon 19 (Del19) and a point mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in NSCLC, approximately 10% of EGFR mutation-positive tumors harbor uncommon mutations. These mutations represent a heterogeneous group of rare molecular alterations (or combinations) within exons 18-21, whose oncogenicity and sensitivity to EGFR TKIs may vary and has not been prospectively studied. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M [11]. In preclinical data, the potency of AZD9291 against uncommon EGFR mutants other than exon 20 insertion mutation was fairly good. Based on the result, in this study, we try to evaluate the efficacy of AZD9291, the potent irreversible inhibitor, in NSCLC patients with harboring uncommon EGFR mutations.

NCT03424759 Non Small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

1 Interventions

Name: AZD9291

Description: Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days).
Type: Drug
Group Labels: 1

AZD9291


Primary Outcomes

Description: 30%

Measure: Objective response rate

Time: through study completion, an average of 2 years

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There are 2 SNPs

SNPs


1 L858R

While in-frame deletion in exon 19 (Del19) and a point mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in NSCLC, approximately 10% of EGFR mutation-positive tumors harbor uncommon mutations. --- L858R ---

Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M [11]. --- L858R ---

Inclusion Criteria: - Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20 - metastatic or recurrent NSCLC - Be 19years of age on day of signing informed consent - ECOG performance status of 0 to 2 - At least one measurable lesion by RECIST 1.1(The part of radiation treatment in the palliative setting is excluded.) --- L858R ---

- Untreated asymptomatic brain metastasis or symptomatic brain metastasis treated with local treatment such as operation, whole brain radiotherapy, or gamma-knife surgery - At least 2 weeks later after whole brain radiotherapy or at least 4 weeks later after palliative thoracic radiotherapy - Adequate organ function as evidenced by the following; Absolute neutrophil count > 1.5 x 109/L; Hb > 9.0g/dL; platelets > 100 x 109/L; total bilirubin ≤1.5 UNL; AST and/or ALT < 2.5 ULN if no demonstrable liver metastases or < 5 UNL in the presence of liver metastases, CCr ≥ 50mL/min - Written informed consent form Exclusion Criteria: - Prior treatment with EGFR TKI - Major surgery undertaken less than 4 weeks before the study - Localized palliative radiotherapy unless completed more than 2 weeks before the study - Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia - Pregnant or nursing women (Women of reproductive potential have to agree to use an adequate contraceptive method) - Uncontrolled symptomatic brain metastasis - Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, or well-treated thyroid cancer - Concomitant use of CYP3A4 inducers/inhibitors - Prolonged QT interval in ECG (QTc >450 msec) - Prior history of interstitial lung disease Inclusion Criteria: - Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20 - metastatic or recurrent NSCLC - Be 19years of age on day of signing informed consent - ECOG performance status of 0 to 2 - At least one measurable lesion by RECIST 1.1(The part of radiation treatment in the palliative setting is excluded.) --- L858R ---

Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M (9). --- L858R ---


2 T790M

Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M [11]. --- L858R --- --- T790M ---

Inclusion Criteria: - Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20 - metastatic or recurrent NSCLC - Be 19years of age on day of signing informed consent - ECOG performance status of 0 to 2 - At least one measurable lesion by RECIST 1.1(The part of radiation treatment in the palliative setting is excluded.) --- L858R --- --- T790M ---

- Untreated asymptomatic brain metastasis or symptomatic brain metastasis treated with local treatment such as operation, whole brain radiotherapy, or gamma-knife surgery - At least 2 weeks later after whole brain radiotherapy or at least 4 weeks later after palliative thoracic radiotherapy - Adequate organ function as evidenced by the following; Absolute neutrophil count > 1.5 x 109/L; Hb > 9.0g/dL; platelets > 100 x 109/L; total bilirubin ≤1.5 UNL; AST and/or ALT < 2.5 ULN if no demonstrable liver metastases or < 5 UNL in the presence of liver metastases, CCr ≥ 50mL/min - Written informed consent form Exclusion Criteria: - Prior treatment with EGFR TKI - Major surgery undertaken less than 4 weeks before the study - Localized palliative radiotherapy unless completed more than 2 weeks before the study - Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia - Pregnant or nursing women (Women of reproductive potential have to agree to use an adequate contraceptive method) - Uncontrolled symptomatic brain metastasis - Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, or well-treated thyroid cancer - Concomitant use of CYP3A4 inducers/inhibitors - Prolonged QT interval in ECG (QTc >450 msec) - Prior history of interstitial lung disease Inclusion Criteria: - Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20 - metastatic or recurrent NSCLC - Be 19years of age on day of signing informed consent - ECOG performance status of 0 to 2 - At least one measurable lesion by RECIST 1.1(The part of radiation treatment in the palliative setting is excluded.) --- L858R --- --- T790M ---

Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M (9). --- L858R --- --- T790M ---



HPO Nodes


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