Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The first treatment is usually chemotherapy, given with another treatment that targets specific proteins on cancer cells. If the cancer gets worse, the next main treatment is usually a medicine called docetaxel. This treatment doesn't stop most people's cancer from getting worse for very long. Other treatments are needed to improve outcomes in people with NSCLC.
Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Many people with NSCLC have a faulty KRAS gene in their tumor. One such change in the KRAS gene is called a G12D mutation. Researchers are looking for ways to stop the actions of abnormal proteins made from the KRAS G12D mutation.
Setidegrasib (ASP3082) is thought to remove some of the abnormal proteins made from the faulty KRAS gene. Before setidegrasib can become available as a treatment, studies need to be done.
This study is for people with NSCLC with a faulty KRAS gene in their tumor. In this study, some people will be given setidegrasib and some people will be given docetaxel. The main aims are to learn how long people who are given setidegrasib live with cancer without it getting worse, compared to people who are given docetaxel, and if they live for longer. Other aims are to check tumor response, symptoms, how the body processes setidegrasib, and its safety, compared with docetaxel.
The main aims of study are to learn how long people who are given setidegrasib live with cancer without it getting worse, compared to people who are given docetaxel and if people who are given setidegrasib live for longer compared to people who are given docetaxel.
People in this study will be adults with locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC) with the G12D mutation in their KRAS gene. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. They have had no more than 2 previous treatments for their cancer. The key reasons people cannot take part are if they have different faulty genes in their tumor which can be targeted with other treatments, have symptomatic or untreated cancers that have spread from the lung into the brain or nervous system, their cancer has spread to the thin tissue that covers the brain and spinal cord (leptomeningeal disease), or they have recently had other active cancers that required treatment.
In this study, people will either receive setidegrasib or docetaxel. Whether people receive setidegrasib or docetaxel is decided by chance, not by the study doctor. Both study treatments are given slowly through a tube into a vein (infusion). People will continue to receive study treatment until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly, they pass away. Some people on docetaxel may be able to switch to setidegrasib during the study if their cancer becomes worse. There will be safety checks at each visit, and the doctors will continue to check for medical problems and people's wellbeing throughout the study. People will continue to have scans of their tumor every 6 weeks for the first year, then every 9 weeks until their cancer becomes worse. After people's cancer becomes worse, clinic staff will telephone people every 12 weeks to check on their cancer.
Participant has histologically confirmed locally advanced (unresectable) or metastatic non-small cell lung cancer (NSCLC) with documented Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutation result status, based on local or central testing.
The participant's positive KRAS G12D mutation result (either in tumor tissue or plasma ctDNA) must be available prior to randomization.
If the participant is enrolling based on a local testing result, the result may have been based on tissue or liquid (blood) testing. If the participant is enrolling via central testing, the eligibility sample must be from tissue.
Participant must have progressed or experienced disease recurrence on or after platinum based chemotherapy (which includes but is not limited to platinum combinations with pemetrexed, paclitaxel, etoposide or gemcitabine) in combination with anti-PD-1/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1 antibody (in either order) sequentially in the locally advanced (unresectable) or metastatic setting (participant who received anti PD-1/anti-PD-L1 antibody or platinum-based chemotherapy as first-line therapy in the locally advanced [unresectable] or metastatic setting may have received the combination of platinum-based chemotherapy and anti PD1/anti PD L1 antibody in the second line locally advanced [unresectable] or metastatic setting).
Participant has known untreated or symptomatic central nervous system (CNS) metastases. Participant with previously treated brain metastases may be eligible if they have stable CNS disease for ≥ 2 weeks prior to randomization, all neurologic symptoms have returned to baseline, there is no evidence of new or enlarging brain metastases on brain imaging performed within 28 days prior to randomization and they are receiving ≤ 10 mg/day of prednisone or equivalent. Participants with untreated CNS metastases, even if asymptomatic, are not eligible.
Participant has mixed small-cell lung cancer and NSCLC histology.
Participant has leptomeningeal disease as a manifestation of the current malignancy.
Participant has another prior malignancy active (i.e., requiring treatment, including hormonal therapies, or intervention) within the previous 2 years different from the primary malignancy for this study, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed.