This study involves people with a type of lung cancer called Non-Small-Cell Lung Cancer that has spread to other parts of the body or has grown in a way that cannot be removed by surgery or treated with radiation therapy alone. The cancer has specific uncommon changes in a protein called Epidermal Growth Factor Receptor, known as PACC mutations, which affect how cancer cells grow. The study will test a medicine called firmonertinib, which is also known by other names including alflutinib, and compare it with one of two other medicines that doctors already use to treat this type of lung cancer. These comparison medicines are osimertinib and afatinib, and the doctor treating each person will choose which one to use. All of these medicines are taken by mouth as tablets.

The purpose of the study is to find out if firmonertinib works better than the doctor’s choice of osimertinib or afatinib in stopping the cancer from getting worse, and to see how many people respond to the treatment. The study will also look at how safe these medicines are and what side effects they may cause. People taking part will receive one of these medicines as their first treatment for cancer that has spread or grown too much to be cured by surgery or radiation.

During the study, people will be divided into groups by chance, similar to flipping a coin, and will receive either firmonertinib or the doctor’s choice of osimertinib or afatinib. Treatment can continue for up to 18 months or longer if the medicine is helping to control the cancer. Throughout the study, doctors will monitor how well the treatment is working and check for any side effects. Both the people in the study and their doctors will know which medicine is being given, as this is not a blinded study.