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Report for Clinical Trial NCT03529084

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Randomized, Open-label, Phase III Study of Single Agent Nazartinib Versus Investigator's Choice (Erlotinib or Gefitinib) as First-Line Treatment in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Activating Mutations

This is a phase III, open label, randomized controlled multi-center global study designed to evaluate the safety and efficacy of single agent nazartinib (EGF816) compared with investigator's choice (erlotinib or gefitinib) in patients with locally advanced or metastatic NSCLC who are treatment naïve and whose tumors harbor EGFR activating mutations (L858R or ex19del).

NCT03529084 Carcinoma, Non-small Cell Lung
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

2 Interventions

Name: EFG816

Description: It will be administered orally daily.
Type: Drug
Group Labels: 1

EGF816

Name: erlotinib or gefitinib

Description: Investigator's choice between erlotinib or gefitinib. These will be locally sourced. Erlotinib will be administered orally daily. Gefitinib will be administered orally daily.
Type: Drug
Group Labels: 1

Investigator's Choice


Primary Outcomes

Description: PFS using central BIRC assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by BIRC per RECIST 1.1) or death due to any cause, whichever occurs first.

Measure: Progression Free Survival (PFS) by Blinded independent review committee (BIRC)

Time: Approximately 3 years

Secondary Outcomes

Description: Overall survival is defined as the time from date of randomization to date of death due to any cause.

Measure: Overall Survival

Time: Approximately 6 years

Description: PFS by Investigator assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by Investigator per RECIST 1.1) or death due to any cause, whichever occurs first.

Measure: PFS by investigator

Time: Approximately 3 years

Description: PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1 is defined as time from date of randomization to the first documented disease progression (clinical or radiologic) as per investigator assessment on next-line therapy or death from any cause, whichever occurs first.

Measure: PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1

Time: Approximately 4 years

Description: Time to progression in CNS, defined as time from date of randomization to the date of first documented progression of brain metastases as assessed by central neuro-radiologist BIRC per modified RECIST 1.1 for patients with at least one non-measurable and/or measurable lesion in the brain at baseline.

Measure: Time to progression in Central Nervous System (CNS) per central neuro-radiologist BIRC

Time: Approximately 3 years

Description: ORR in accordance with RECIST 1.1. ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR)

Measure: Overall response rate (ORR) by central BIRC

Time: Approximately 3 years

Description: DOR is defined as the time from date of first documented response (CR and PR) to the date of the first documented progression or death due to underlying cancer, whichever occurs first.

Measure: Duration of response (DOR) by central BIRC

Time: Approximately 3 years

Description: DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD).

Measure: Disease control rate (DCR) by central BIRC

Time: Approximately 3 years

Description: TTR is defined as the time from the date of randomization to the first documented response CR or PR.

Measure: Time to response (TTR) by central BIRC

Time: Approximately 3 years

Description: CNS ORR in patients with brain metastases who have measurable disease in the brain at baseline review per modified RECIST 1.1

Measure: CNS ORR per central neuro-radiologist BIRC

Time: Approximately 3 years

Description: CNS DoR in patients with brain metastases who have measurable disease in the brain at baseline per modified RECIST 1.1

Measure: CNS DoR per central neuro-radiologist BIRC

Time: Approximately 3 years

Description: Peak plasma concentration (Cmax) of EGF816 and its metabolite (LMI258)

Measure: Charactise Plasma PK (Cmax) of EGF816

Time: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)

Description: Area under the plasma concentration versus time curve (AUC) of EGF816 and its metabolite (LMI258)

Measure: Charactise Plasma PK (AUC) of EGF816

Time: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)

Description: Elimination half life (t1/2) of EGF816 and its metabolite (LMI258)

Measure: Charactise Plasma PK (t1/2) of EGF816

Time: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)

Description: HRQoL as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life score

Measure: Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-C30 Questionnaire

Time: Approximately 4 years

Description: HRQoL as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 quality of life score

Measure: Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-LC13 Questionnaire

Time: Approximately 4 years

Description: Global health status/quality of life score of the EQ-5D-5L

Measure: Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by EuroQoL-5 Dimension-5 (EQ-5D-5L) Questionnaire

Time: Approximately 4 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 L858R

Phase III Study of Nazartinib (EGF816) Versus Erlotinib/Gefitinib in First-line Locally Advanced / Metastatic NSCLC With EGFR Activating Mutations This is a phase III, open label, randomized controlled multi-center global study designed to evaluate the safety and efficacy of single agent nazartinib (EGF816) compared with investigator's choice (erlotinib or gefitinib) in patients with locally advanced or metastatic NSCLC who are treatment naïve and whose tumors harbor EGFR activating mutations (L858R or ex19del). --- L858R ---

- Histologically documented locally advanced or metastatic, stage IIIB/ IIIC or stage IV NSCLC with documented EGFR activating mutation (L858R or ex19del) - Provision of a tumor tissue sample to allow for retrospective analysis of EGFR mutation status - No prior treatment with any systemic antineoplastic therapy in the advanced setting - Recovered from all toxicities related to prior treatment - Presence of at least one measurable lesion according to RECIST 1.1 - Eastern Cooperative Oncology Group (ECOG) performance ≤1 - Meet the following laboratory values at the screening visit: - Absolute Neutrophil Count ≥1.5 x 109/L - Platelets ≥75 x 109/L - Hemoglobin (Hgb) ≥9 g/dL - Creatinine Clearance ≥ 45 mL/min using Cockcroft-Gault formula - Total bilirubin ≤1.5 x ULN - Aspartate transaminase (AST) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST ≤5.0 x ULN - Alanine transaminase (ALT) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if ALT ≤5.0 x ULN Exclusion Criteria: - Prior treatment with EGFR-TKI. --- L858R ---

Any other known EGFR activating mutations other than L858R or ex19del. --- L858R ---

Patients whose tumors harbor other EGFR mutations concurrent with L858R or ex19del EGFR mutations are eligible. --- L858R ---


2 T790M

- Known T790M positive mutation. --- T790M ---



HPO Nodes


HPO: