Your diagnosis of pleural mesothelioma (a cancer affecting the lining of the lungs) will be confirmed through tissue samples obtained during a thoracoscopy biopsy (a procedure where samples are taken from the chest). At least 10 slides from your biopsy sample must be available for analysis.

Your disease will be evaluated to confirm it cannot be removed by surgery. This evaluation will be performed by a specialized team including a thoracic surgeon.

Imaging tests, specifically a CT scan with contrast (a detailed x-ray using a special dye), will be performed to measure your disease according to specific criteria. The disease must be measurable, either as thickening of the pleural lining of at least 7 millimeters in multiple locations, or as enlarged lymph nodes or other affected areas.

Your overall health status will be assessed using the ECOG performance status scale, which measures your ability to perform daily activities. You must have a score of 0 or 1, meaning you are fully active or have some restrictions but can perform light work.

Blood tests will be performed to check your organ function, including kidney function (creatinine clearance must be at least 45 milliliters per minute), blood cell counts (white blood cells, platelets, and hemoglobin levels), and liver function tests.

If you are a woman of childbearing potential, a pregnancy test will be performed and must be negative.

If you had a procedure to drain fluid from your chest (thoracocentesis) or a thoracoscopy within 2 months before joining the trial, you should receive radiation therapy to the procedure sites. This involves 3 sessions of 7 Gray each. There should be no more than 42 days between the removal of any drains and the start of radiation. A 7-day waiting period is required between the end of radiation therapy and the start of trial treatment.

You will be assigned to one of two treatment groups. This is a non-comparative trial, meaning the groups are not being directly compared against each other but are being evaluated separately.

One group receives fianlimab plus cemiplimab plus chemotherapy (pemetrexed and platinum-based drug).

The other group receives cemiplimab plus chemotherapy (pemetrexed and platinum-based drug).

All medications in this trial are given through intravenous infusion, meaning they are administered directly into a vein.

Fianlimab is provided as a solution for injection and will be given intravenously if you are assigned to the group receiving this medication.

Cemiplimab (also known as LIBTAYO) is provided as a 350 milligram concentrate that is prepared as a solution for infusion and will be given intravenously.

The chemotherapy consists of pemetrexed and a platinum-based drug, both given intravenously.

The specific dosage amounts, frequency of administration, and total duration of treatment are determined by the trial protocol and will be explained to you by your medical team.

Throughout the trial, you will have regular visits for monitoring and assessments.

Imaging scans will be performed at scheduled intervals to evaluate how your disease is responding to treatment. These assessments will use RECIST 1.1 criteria modified for mesothelioma, which is a standardized method for measuring tumor response.

Your scans will be reviewed by both your treating physician and an Independent Review Committee, which is a separate group of specialists who evaluate the images independently.

At 6 months, your disease status will be assessed to determine the Disease Control Rate, which measures whether your disease has responded to treatment, remained stable, or progressed.

Blood tests and physical examinations will be conducted regularly to monitor your health and check for any side effects.

Any side effects or adverse events you experience will be recorded and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0, which is a standard system for classifying the severity of side effects.

Quality of life questionnaires will be completed at various time points to assess changes in your symptoms and daily functioning. These include the EQ-5D-5L and LCSS-meso questionnaires.

If you are a woman of childbearing potential, you must use effective contraception during the entire trial and for 6 months after receiving the last dose of treatment.

If you are a male participant with a female partner of childbearing potential, you must use condoms during the trial and for 6 months after the last dose of treatment, unless you have had a vasectomy.

Women must agree not to donate eggs during the trial and for 6 months after the last treatment.

Men must agree not to donate sperm during the trial and for 6 months after receiving the last dose.

After completing treatment, you will continue to be followed to assess long-term outcomes.

Progression-Free Survival will be measured, which is the length of time you live without your disease getting worse.

Overall Survival will be tracked, which is the length of time you live from the start of treatment.

The response of your disease will be categorized according to your specific histological subtype (epithelioid or non-epithelioid), which refers to the type of cells in your mesothelioma.

Any instances of Hyper-Progressive Disease (unusually rapid disease progression) will be documented.