This clinical trial is studying Non-Small Cell Lung Cancer with a KRAS G12C change, including cancer that has been removed by surgery and cancer that cannot be removed. The treatment being tested is olomorasib, also called LY3537982, taken by mouth, given together with standard cancer immunotherapy medicines. In one part of the study, pembrolizumab is used, and in another part, durvalumab is used; some participants receive placebo with these medicines instead of olomorasib.
The purpose of the study is to see whether olomorasib, when added to standard immunotherapy, works better and is safe for people with this type of lung cancer. The study is done in different parts. After treatment begins, participants are followed over time while taking the study medicine or placebo together with the immunotherapy medicine, and health checks are done throughout the study to watch for side effects and any changes in the cancer.
1study treatment assignment
After joining the study, you are assigned to one of the study treatment groups. The study is double-blind, which means that neither you nor the study team knows whether you receive the study drug or the placebo, unless there is a medical reason to know.
In part a, you receive either olomorasib (ly3537982) by mouth in capsule form or a placebo that matches olomorasib, together with pembrolizumab by intravenous use (given through a vein).
In part b, you receive either olomorasib (ly3537982) by mouth in capsule form or a placebo that matches olomorasib, together with durvalumab by intravenous use (given through a vein).
The source data lists the study products and routes of administration, but it does not specify the dose, frequency, or duration of each medicine.
2treatment period
During the trial, you continue receiving the assigned combination of medicines for your study part: either olomorasib or placebo by mouth, plus either pembrolizumab or durvalumab through a vein.
The study compares olomorasib plus pembrolizumab with placebo plus pembrolizumab in part a, and olomorasib plus durvalumab with placebo plus durvalumab in part b.
The source data does not give a specific calendar schedule for how often the medicines are taken or infused, and it does not state how long the treatment is continued.
3assessment of the study outcome
Your progress in the study is measured during treatment. In part a, the main outcome is disease-free survival, which means the length of time after treatment when no signs of cancer are found. This is checked by the investigator, meaning the study doctor or study clinician reviewing your results.
In part b, the main outcome is pfs, which stands for progression-free survival. This means the length of time during which the cancer does not get worse. This is checked by bicr, which stands for blinded independent central review; this means a review by specialists who do not know which treatment you received.
The source data does not provide additional stage-by-stage visit details beyond these study measurements.
4study completion
The trial is planned to continue until the study ends. The estimated study dates in the source data run from 2025-05-12 to 2032-02-28.
The source data does not describe any further steps after the treatment and outcome assessments.
Who Can Join the Study?
Have a confirmed diagnosis of non-small cell lung cancer (NSCLC) based on tissue or cell testing. This means the cancer must have been proven by looking at a sample under a microscope.
Have cancer with a confirmed KRAS G12C mutation, which is a specific change in the cancer cells’ genes.
Have a known PD-L1 level. PD-L1 is a protein found on some cancer cells that helps doctors decide on treatment.
Have an ECOG performance status of 0 or 1. This means the person must be fully active or only mildly limited in daily activities.
Be able to swallow oral medication, meaning medicine taken by mouth.
Have adequate laboratory parameters, meaning blood tests and other lab results must be within the required safe range for the study.
For Part A, have Stage II to IIIB (N2) disease that was treated with presurgical chemoimmunotherapy, meaning chemotherapy and immunotherapy were given before surgery, and there is still tumor left at the time of surgery.
For Part A, people with a pathologic complete response are not eligible. This means the surgery sample must still show cancer, because a complete disappearance of cancer cells in the tissue sample does not qualify.
For Part A, have Stage II to IIIB (N2) disease that was treated with initial upfront resection, meaning the tumor was removed by surgery first.
For Part B, have Stage III, unresectable non-small cell lung cancer. Unresectable means the cancer cannot be removed by surgery.
For Part B, have had concurrent platinum-based chemoradiotherapy without the disease getting worse. This means chemotherapy with a platinum medicine and radiation were given at the same time, and the cancer did not progress.
Follow contraception rules required by local study regulations. Contraception means methods used to prevent pregnancy.
If the person is a woman who can become pregnant, she must have a negative pregnancy test.
If the person is a woman who can become pregnant, she must not be breastfeeding during treatment.
Who Cannot Join the Study?
Known changes in the EGFR or ALK genes. These are specific gene changes that can affect how cancer behaves and how treatments work.
Another type of cancer that is getting worse or needed active treatment within the past 3 years before the screening visit. Active treatment means treatment that is currently being given, such as surgery, chemotherapy, radiation, or other cancer therapy.
An active autoimmune disease that needed systemic treatment in the past 2 years. An autoimmune disease is a condition where the immune system attacks the body. Systemic treatment means treatment that affects the whole body, such as pills or injections that lower immune system activity. Endocrine replacement therapy is allowed; this means hormone replacement treatment for gland-related hormone problems.
Any past immune-related side effect or allergic reaction of Grade 3 or higher from a previous immunotherapy medicine. Grade 3 or higher means a severe reaction. Immunotherapy is a cancer treatment that helps the immune system fight cancer.
Any immune-related side effect worse than Grade 1 that has not gone away. Grade 1 means a mild effect; anything worse than that is more than mild. This does not apply to people with hormone-related diseases who are now stable on hormone replacement treatment.
LY3537982 is the study medicine being tested in this trial. It is taken by mouth as a capsule and is being studied to see if it helps treat KRAS G12C mutant non-small cell lung cancer when given together with standard immunotherapy. It is the main medicine whose benefits and safety are being compared in the trial.
Pembrolizumab is an immunotherapy medicine given through a vein. It helps the body’s immune system recognize and attack cancer cells. In this trial, it is given with the study medicine to see whether the combination works better than treatment without the study medicine.
Durvalumab is another immunotherapy medicine given through a vein. It also helps the immune system fight cancer. In this trial, it is used with the study medicine in a second part of the study to compare this combination against treatment without the study medicine.
Resected or Unresectable KRAS G12C-Mutant Non-Small Cell Lung Cancer – This is a type of non-small cell lung cancer that contains a specific change in the KRAS gene called G12C. It may be found either after surgical removal of the tumor or in a form that cannot be removed by surgery. The disease usually begins in the cells lining the airways or air sacs of the lung. It can grow within the lung and spread to nearby lymph nodes or other parts of the body over time. In some people, it may remain localized for a period, while in others it progresses more quickly.
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