We are doing this study to find the most effective, safe dose of an experimental drug called amivantamab (the study drug) when it is given in combination with lazertinib and chemotherapy. We want to know if this study drug regimen is effective for people with non-small cell lung cancer (NSCLC) who have a specific mutation in the EGFR (epidermal growth factor receptor) gene.

Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with EGFR Mutations

Adults ages 18+ who:

• Are diagnosed with advanced or metastatic NSCLC)
• Have a documented EGFR mutation (specifically, an Ex19del or Ex21 L858R substitution)
• Do not have an adequate response to standard curative therapy
• Do not have interstitial lung disease or any form of chronic liver disease

For more information, contact the study team at annemarie.peters@duke.edu.

This study consists of 2 cohorts, Cohort 1 and Cohort 2.

Cohort 1
If you choose to join this study and take part in Cohort 1, you will:

• Get the study drug as an injection (shot under the skin)
• Take lazertinib tablets once each day
• Take an an oral or injectable medication during the first 4 months of study drug to prevent or reduce the likelihood and severity of blood clots
• Take medications to prevent the known possible side effects of the study drug and lazertinib (e.g., skin and/or nail rash)

Cohort 2
If you choose to join this study and take part in Cohort 2, you will:

• Get the study drug as an injection (shot under the skin)
• Get chemotherapy (carboplatin and pemetrexed)
• Take medications to prevent the known possible side effects of the study drug (e.g., skin and/or nail rash)

During the study visits the following procedures may occur: physical exam, vital signs, electrocardiograms, tumor imaging (CT/MRI), questionnaires, blood draws, and tumor biopsy. The duration of your involvement in the study will vary depending on how you and your disease respond to the study drug. Participation might last as long as 3 years. During the first year, you can expect to visit the study site around 20 times. Afterward, visits will occur every 3 weeks until you stop the study regimen. Following that, visits will be scheduled every 12 weeks until the study concludes.