The purpose of this study is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions [Exon 19del] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-small cell lung cancer (NSCLC).
Name: Amivantamab
Name: Osimertinib
Name: Lazertinib
Name: Placebo
Description: PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occured first, based on BICR using response evaluation criteria in solid tumors (RECIST) v1.1.
Measure: Progression-Free Survival (PFS) According to RECIST v1.1 by Blinded Independent Central Review (BICR) Time: Up to approximately 42 monthsDescription: Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.
Measure: Overall Survival (OS) Time: Up to approximately 60 months (time from the date of randomization until the date of death due to any cause)Description: ORR is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as defined by BICR using RECIST v1.1 criteria.
Measure: Objective Response Rate (ORR) Time: Up to approximately 42 monthsDescription: DOR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST v1.1 criteria.
Measure: Duration of Response (DOR) Time: Up to approximately 42 monthsDescription: The PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.
Measure: Progression-Free Survival After First Subsequent Therapy (PFS2) Time: Up to approximately 42 monthsDescription: TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms.
Measure: Time to Symptomatic Progression (TTSP) Time: Up to approximately 42 monthsDescription: Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1.
Measure: Intracranial PFS Time: Up to approximately 42 monthsDescription: Incidence and severity of treatment emergent adverse events (TEAEs) will be reported. Any adverse event occurring at or after the initial administration of study treatment through the day of last dose plus 30 days, or until the start of subsequent anticancer therapy (if earlier), is considered to be treatment emergent.
Measure: Incidence and Severity of Adverse Events (AEs) Time: Up to approximately 60 monthsDescription: Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urine samples) will be reported.
Measure: Number of Participants with Clinical Laboratory Abnormalities Time: Up to approximately 60 monthsDescription: Number of participants with vital signs abnormalities (temperature, heart rate, respiratory rate, oxygen saturation, blood pressure) will be reported.
Measure: Number of Participants with Vital Signs Abnormalities Time: Up to approximately 60 monthsDescription: Number of participants with physical examination abnormalities will be reported.
Measure: Number of Participants with Physical Examination Abnormalities Time: Up to approximately 60 monthsDescription: Serum samples will be analyzed to determine concentrations of amivantamab.
Measure: Serum Concentration of Amivantamab Time: Up to approximately 42 monthsDescription: Plasma samples will be analyzed to determine concentrations of lazertinib.
Measure: Plasma Concentration of Lazertinib Time: Up to approximately 42 monthsDescription: Number of participants with antibodies to amivantamab will be reported.
Measure: Number of Participants with Anti-Amivantamab Antibodies Time: Up to approximately 42 monthsDescription: The NSCLC-SAQ contains 7 items that assess cough, pain, dyspnea, fatigue, and poor appetite over a 7-day recall period. Each multi-item scale and individual item will be summarized using count and percent by visit.
Measure: Change from Baseline in Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NCSLC-SAQ) Time: Baseline Up to approximately 42 monthsDescription: EORTC-QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies.
Measure: Change from Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Time: Baseline Up to approximately 42 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer The purpose of this study is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions [Exon 19del] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-small cell lung cancer (NSCLC). --- L858R ---
EORTC-QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies.. Inclusion Criteria: - Participant must have histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC) not amenable to curative therapy - Participant must have a tumor that was previously determined to have exon 19 deletions (Exon 19del) or Exon 21 L858R substitution, as detected by an food and drug administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United states [US]) or an accredited local laboratory (sites outside of the US) in accordance with site standard of care. --- L858R ---
A participant with asymptomatic or previously treated and stable brain metastases may participate in this study Inclusion Criteria: - Participant must have histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC) not amenable to curative therapy - Participant must have a tumor that was previously determined to have exon 19 deletions (Exon 19del) or Exon 21 L858R substitution, as detected by an food and drug administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United states [US]) or an accredited local laboratory (sites outside of the US) in accordance with site standard of care. --- L858R ---
Lazertinib inhibits primary activating Exon 19dell and Exon 21 L858R substitution EGFR mutations, and the EGFR T790M+ resistance mutation. --- L858R ---