SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT04248829

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib Versus Gefitinib as the First-line Treatment in Patients With Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This Phase III study will be conducted to evaluate the efficacy and safety of YH25448 as first-line treatment in locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) patients with EGFR mutations

NCT04248829 Non-Small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

4 Interventions

Name: Lazertinib 240 mg/160 mg

Description: The initial dose of lazertinib 240 mg (3 tablets of 80 mg lazertinib) once daily can be reduced to 160 mg once daily (2 tablets of 80 mg lazertinib) under specific circumstances
Type: Drug
Group Labels: 1

Lazertinib + Gefitinib-matching placebo

Name: Gefitinib 250 mg

Description: The initial dose for Gefitinib (250 mg once daily) cannot be reduced to a lower dose
Type: Drug
Group Labels: 1

Gefitinib + Lazertinib-matching placebo

Name: Lazertinib-matching placebo 240 mg/160 mg

Description: The initial dose of lazertinib-matching placebo 240 mg (3 tablets of 80 mg lazertinib-matching placebo) once daily can be reduced to 160 mg once daily (2 tablets of 80 mg lazertinib-matching placebo) under specific circumstances
Type: Drug
Group Labels: 1

Gefitinib + Lazertinib-matching placebo

Name: Gefitinib-matching placebo 250 mg

Description: The initial dose for Gefitinib-matching placebo (250 mg once daily) cannot be reduced to a lower dose
Type: Drug
Group Labels: 1

Lazertinib + Gefitinib-matching placebo


Primary Outcomes

Description: To assess the efficacy of lazertinib compared with gefitinib as measured by PFS

Measure: Progression-Free Survival (PFS) according to RECIST v1.1 by Investigator assessment

Time: The primary analysis of PFS based on investigator assessment will occur when PFS maturity is observed at approximately 27 months after the first patient is randomized

Secondary Outcomes

Description: To further assess the efficacy of lazertinib compared with gefitinib

Measure: Objective Response Rate (ORR) according to RECIST v1.1 by Investigator assessments

Time: ORR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To further assess the efficacy of lazertinib compared with gefitinib

Measure: Duration of Response (DoR) according to RECIST v1.1 by Investigator assessments

Time: DoR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To further assess the efficacy of lazertinib compared with gefitinib

Measure: Disease Control Rate (DCR) according to RECIST v1.1 by Investigator assessments

Time: DCR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To further assess the efficacy of lazertinib compared with gefitinib

Measure: Depth of Response according to RECIST v1.1 by Investigator assessments

Time: Depth of Response analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To further assess the efficacy of lazertinib compared with gefitinib

Measure: Time to Response according to RECIST v1.1 by Investigator assessments

Time: Time to Response analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To assess OS of lazertinib compared with gefitinib

Measure: Overall survival (OS)

Time: OS will be analyzed at 2 time points: when PFS maturity is observed at approximately 27 months after the first patient is randomized, and when OS maturity is observed at approximately 45 months after the first patient is randomized

Description: To characterize the pharmacokinetics (PK) of lazertinib

Measure: Plasma concentrations of lazertinib

Time: Plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To characterize the PK of lazertinib metabolite YH26334

Measure: Plasma concentrations of Metabolite YH26334

Time: Plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To characterize the PK of lazertinib and YH26334

Measure: Ratio of YH26334 to lazertinib plasma concentration

Time: Ratio of YH26334 to lazertinib plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To characterize the PK of lazertinib

Measure: Cerebrospinal fluid (CSF) concentrations of lazertinib

Time: CSF concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To characterize the PK of lazertinib metabolite YH26334

Measure: CSF concentrations of Metabolite YH26334

Time: CSF concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To characterize the PK of lazertinib and YH26334

Measure: Ratio of CSF to plasma concentration of lazertinib and YH26334

Time: Ratio of CSF to plasma concentration analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: The EORTC QLQ-C30 consists of 30 items and measures cancer patients' functioning (health related quality of life (HRQoL)) and symptoms for all cancer types. Questions can be grouped into 5 multi item functional scales (physical, role, emotional, cognitive, and social); 3 multi item symptom scales (fatigue, pain, nausea/vomiting); a 2 item global HRQoL scale; 5 single items assessing additional symptoms commonly reported by cancer patients (dyspnea, loss of appetite, insomnia, constipation, diarrhea) and 1 item on the financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. a high score for a functional scale represents a high / healthy level of functioning a high score for the global health status / QoL represents a high QoL but a high score for a symptom scale / item represents a high level of symptomatology / problems

Measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 items (QLQ-C30)

Time: EORTC-QLQ-C30 analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Description: The EORTC QLQ-LC13 includes questions assessing cough, hemoptysis, dyspnea, site specific pain (symptoms), sore mouth, dysphagia, peripheral neuropathy, and alopecia (treatment related side effects), and pain medication. The items on both measures were scaled and scored using the recommended EORTC procedures. Raw scores were transformed to a linear scale ranging from 0 to 100, with a higher score representing a higher level of functioning or higher level of symptoms. Provided at least half of the items in the scale were completed, the scale score was calculated using only those items for which values existed.

Measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13 items (EORTC QLQ-LC13)

Time: EORTC QLQ-LC13 analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Description: The EQ-5D comprises the following two questionnaires: The EQ-5D comprises 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension comprises five levels (no problems, slight problems, moderate problem, severe problem, unable/extreme problems). The EQ VAS records the patients self-rated health status on a vertical graduated (0-100) visual analogue scale. The patient's self-rated health is assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS.

Measure: Change From Baseline in Euro-Quality of Life-5 Dimension-5 level (EQ-5D-5L)

Time: EQ-5D-5L analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Other Outcomes

Description: To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with brain metastases (BM) at baseline

Measure: Intracranial PFS according to RECIST v1.1 by Investigator assessment and blinded independent central review (BICR)

Time: Intracranial PFS based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

Measure: Intracranial ORR according to RECIST v1.1 by Investigator assessments and BICR

Time: Intracranial ORR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

Measure: Intracranial DoR according to RECIST v1.1 by Investigator assessment and BICR

Time: Intracranial DoR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

Measure: Intracranial DCR according to RECIST v1.1 by Investigator assessment and BICR

Time: Intracranial DCR based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

Measure: Depth of intracranial response according to RECIST v1.1 by Investigator assessment and BICR

Time: Depth of intracranial response based on Investigator assessment and BICR analysis will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To assess the intracranial efficacy of lazertinib compared with gefitinib in only patients with BM at baseline

Measure: Time to intracranial response according to RECIST v1.1 by Investigator assessment and BICR

Time: Time to intracranial response analysis based on Investigator assessment and BICR will occur when PFS maturity is observed at approximately 27 months from the first patient being randomized

Description: To assess the efficacy of lazertinib in the cross-over arm

Measure: PFS according to RECIST v1.1 by Investigator assessment

Time: PFS analysis will occur when OS maturity is observed at approximately 45 months from the first dosing date of lazertinib

Description: To assess the efficacy of lazertinib in the cross-over arm

Measure: ORR according to RECIST v1.1 by Investigator assessments

Time: ORR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Description: To assess the efficacy of lazertinib in the cross-over arm

Measure: DoR according to RECIST v1.1 by Investigator assessments

Time: DoR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Description: To assess the efficacy of lazertinib in the cross-over arm

Measure: DCR according to RECIST v1.1 by Investigator assessments

Time: DCR analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Description: To assess the efficacy of lazertinib in the cross-over arm

Measure: Depth of Response according to RECIST v1.1 by Investigator assessments

Time: Depth of Response analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Description: To assess the efficacy of lazertinib in the cross-over arm

Measure: Time to Response according to RECIST v1.1 by Investigator assessments

Time: Time to Response analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Description: To compare plasma-derived cfDNA EGFR mutation status at baseline and at progression

Measure: Change from baseline for EGFR mutation status in plasma samples

Time: EGFR mutation status in plasma samples analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Description: To compare the tumor sample EGFR mutation status at baseline and from an optional tumor sample taken at progression

Measure: Change from baseline for EGFR mutation status in tumor samples

Time: EGFR mutation status in tumor samples analysis will occur when OS maturity is observed at approximately 45 months from the first patient being randomized

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 L858R

Inclusion Criteria: - Pathologically confirmed adenocarcinoma of the lung - Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy - At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations - Treatment-naïve for locally advanced or metastatic NSCLC - WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization - At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period Exclusion Criteria: - Symptomatic and unstable brain metastases - Leptomeningeal metastases - Symptomatic spinal cord compression - History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD - Any medical conditions requiring chronic continuous oxygen therapy - History of any malignancy other than the disease under study within 3 years before randomization - Any cardiovascular disease as follows: - History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment - History of myocardial infarction or unstable angina within 24 weeks of randomization Inclusion Criteria: - Pathologically confirmed adenocarcinoma of the lung - Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy - At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations - Treatment-naïve for locally advanced or metastatic NSCLC - WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization - At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period Exclusion Criteria: - Symptomatic and unstable brain metastases - Leptomeningeal metastases - Symptomatic spinal cord compression - History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD - Any medical conditions requiring chronic continuous oxygen therapy - History of any malignancy other than the disease under study within 3 years before randomization - Any cardiovascular disease as follows: - History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment - History of myocardial infarction or unstable angina within 24 weeks of randomization Non-Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung YH25448 is an oral, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) that targets both the T790M mutation and activating EGFR mutations while sparing wild type EGFR. --- L858R ---

Inclusion Criteria: - Pathologically confirmed adenocarcinoma of the lung - Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy - At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations - Treatment-naïve for locally advanced or metastatic NSCLC - WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization - At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period Exclusion Criteria: - Symptomatic and unstable brain metastases - Leptomeningeal metastases - Symptomatic spinal cord compression - History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD - Any medical conditions requiring chronic continuous oxygen therapy - History of any malignancy other than the disease under study within 3 years before randomization - Any cardiovascular disease as follows: - History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment - History of myocardial infarction or unstable angina within 24 weeks of randomization Inclusion Criteria: - Pathologically confirmed adenocarcinoma of the lung - Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy - At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations - Treatment-naïve for locally advanced or metastatic NSCLC - WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization - At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period Exclusion Criteria: - Symptomatic and unstable brain metastases - Leptomeningeal metastases - Symptomatic spinal cord compression - History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD - Any medical conditions requiring chronic continuous oxygen therapy - History of any malignancy other than the disease under study within 3 years before randomization - Any cardiovascular disease as follows: - History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment - History of myocardial infarction or unstable angina within 24 weeks of randomization Non-Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung YH25448 is an oral, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) that targets both the T790M mutation and activating EGFR mutations while sparing wild type EGFR. --- L858R --- --- L858R ---


2 T790M

Inclusion Criteria: - Pathologically confirmed adenocarcinoma of the lung - Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy - At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations - Treatment-naïve for locally advanced or metastatic NSCLC - WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization - At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period Exclusion Criteria: - Symptomatic and unstable brain metastases - Leptomeningeal metastases - Symptomatic spinal cord compression - History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD - Any medical conditions requiring chronic continuous oxygen therapy - History of any malignancy other than the disease under study within 3 years before randomization - Any cardiovascular disease as follows: - History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment - History of myocardial infarction or unstable angina within 24 weeks of randomization Inclusion Criteria: - Pathologically confirmed adenocarcinoma of the lung - Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy - At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations - Treatment-naïve for locally advanced or metastatic NSCLC - WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization - At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period Exclusion Criteria: - Symptomatic and unstable brain metastases - Leptomeningeal metastases - Symptomatic spinal cord compression - History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD - Any medical conditions requiring chronic continuous oxygen therapy - History of any malignancy other than the disease under study within 3 years before randomization - Any cardiovascular disease as follows: - History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment - History of myocardial infarction or unstable angina within 24 weeks of randomization Non-Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung YH25448 is an oral, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) that targets both the T790M mutation and activating EGFR mutations while sparing wild type EGFR. --- L858R --- --- L858R --- --- T790M ---



HPO Nodes


HPO: