SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03969823

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Whole Genomic Landscape of EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Treated With First-Line Osimertinib (WARRIOR)

This is a phase 2 single-arm, non-randomized multicentre and tissue acquisition study to evaluate acquired resistance mechanisms, efficacy, and safety in advanced, EGFR tyrosine kinase inhibitor-naïve NSCLC patients with EGFR-activating mutations who receive a first-line osimertinib orally at a dose of 80mg once daily.

NCT03969823 Locally Advanced or Metastatic NSCLC

1 Interventions

Name: Tagrisso

Description: Osimertinib 80mg once daily until disease progression

Type: Drug

Osimertinib


Primary Outcomes

Description: Disease progression as defined by investigator assessments according to RECIST1.1

Measure: Proportion of acquired resistance mechanisms to osimertinib at disease progression

Time: Through study completion, an average of 2 years

Secondary Outcomes

Description: AEs/SAEs as defined by NCI CTCAE version 5.0

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: Through study completion, an average of 2 years

Description: PFS as defined as the time from the date of initiation until the date of first documented progression

Measure: Progression-Free Survival (PFS)

Time: Through study completion, an average of 2 years

Description: OS as defined as the time from the date of first dose until death due to any cause

Measure: Overall Survival (OS)

Time: Through study completion, an average of 2 years

Description: ORR using investigator assessments according RECIST1.1

Measure: Objective Response Rate (ORR)

Time: Through study completion, an average of 2 years

Purpose: Other

Single Group Assignment


There are 3 SNPs

SNPs


1 C797S

Acquired resistance to first-line osimertinib is mediated by heterogeneous mechanisms including MET amplification (15%), secondary EGFR mutation including C797S or S768I (7%), PIK3CA mutation (7%), CDK4/6 amplification (5%), KRAS mutation (3%), BRAF mutation (3%), CCND1-3 amplification (3%), CCNE1 amplification (2%), HER2 amplification (2%), and SPTBN1-ALK fusion (1%) using plasma genotyping of FLAURA study (N=91). --- C797S ---


2 L858R

Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedures 2. Male or female must be > 19 years of age 3. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: - Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments - Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution - Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 4. Male subjects should be willing to use barrier contraception (see Restrictions, Section 3.8) 5. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy with local confirmation of the presence of EGFR TKI-sensitizing mutation (EGFR exon 19 deletion or L858R mutation), either alone or in combination with other EGFR mutations excluding EGFR exon 20 insertion mutation 6. Mandatory provision of fresh tumor sample before osimertinib via a biopsy or surgical resection 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 8. Patients must have a life expectancy ≥ 12 weeks. --- L858R ---

Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedures 2. Male or female must be > 19 years of age 3. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: - Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments - Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution - Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 4. Male subjects should be willing to use barrier contraception (see Restrictions, Section 3.8) 5. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy with local confirmation of the presence of EGFR TKI-sensitizing mutation (EGFR exon 19 deletion or L858R mutation), either alone or in combination with other EGFR mutations excluding EGFR exon 20 insertion mutation 6. Mandatory provision of fresh tumor sample before osimertinib via a biopsy or surgical resection 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 8. Patients must have a life expectancy ≥ 12 weeks. --- L858R ---


3 S768I

Acquired resistance to first-line osimertinib is mediated by heterogeneous mechanisms including MET amplification (15%), secondary EGFR mutation including C797S or S768I (7%), PIK3CA mutation (7%), CDK4/6 amplification (5%), KRAS mutation (3%), BRAF mutation (3%), CCND1-3 amplification (3%), CCNE1 amplification (2%), HER2 amplification (2%), and SPTBN1-ALK fusion (1%) using plasma genotyping of FLAURA study (N=91). --- C797S --- --- S768I ---



HPO Nodes