The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
776
Lazertinib will be administered orally.
Amivantamab will be administered as an IV infusion.
Pemetrexed will be administered as an IV infusion.
Carboplatin will be administered as an IV infusion.
Southern Cancer Center, PC
Mobile, Alabama, United States
Arizona Oncology Associates
Tucson, Arizona, United States
City of Hope
Duarte, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
University of California Irvine
Orange, California, United States
Main Study: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
PFS is defined as the time from randomization until the date of objective disease progression or death, whichever came first, as assessed by BICR according to RECIST version 1.1. Progressed disease: Sum of diameters increased by greater than or equal to (\>=)20 percent (%) and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum).
Time frame: From randomization to either disease progression or death, whichever occurred first (up to 1 year 7 months)
Main Study + Extension Cohort: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Follow-up for the extension cohort is still ongoing and thus results from the analysis that includes the extension cohort will be reported up on study completion.
Time frame: up to 4 years 10 months
Main Study + Extension Cohort: Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Objective Response Rate as Assessed by Blinded Independent Central Review
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Overall Survival
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Duration of Response as Assessed by Blinded Independent Central Review
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Time to Subsequent Therapy
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Progression-free Survival (PFS) After First Subsequent Therapy (PFS2)
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Time to Symptomatic Progression
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Intracranial Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review
Time frame: Up to 4 years 10 months
Main Study: Number of Participants With Adverse Events (AEs)
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Number of Participants With Adverse Events (AEs) by Severity
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Number of Participants With Clinical Laboratory Abnormalities
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Serum Concentration of Amivantamab
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Plasma Concentration of Lazertinib
Time frame: Up to 4 years 10 months
Main Study + Extension Cohort: Number of Participants With Serum Anti-amivantamab Antibodies
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Change From Baseline With Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Change From Baseline With European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Time frame: Up to 4 years 10 months
Main Study+ Extension Cohort: Change From Baseline With Patient-Reported Outcomes Measurement Information System -Physical Function (PROMIS-PF)
Time frame: Up to 4 years 10 months
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Rocky Mountain Cancer Centers
Colorado Springs, Colorado, United States
Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center
Fort Lauderdale, Florida, United States
University Cancer And Blood Center LLC
Athens, Georgia, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Nebraska Cancer Specialists
Grand Island, Nebraska, United States
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