This phase occurs before surgery. Treatment will be administered through intravenous infusion, which means medication will be delivered directly into a vein.

The treatment consists of pembrolizumab combined with platinum-based doublet chemotherapy. Platinum-based chemotherapy may include medications such as carboplatin or cisplatin, combined with another chemotherapy drug such as gemcitabine, paclitaxel, or pemetrexed.

Supportive medications may be provided to manage side effects, including paracetamol for pain relief and h2-receptor antagonists to protect the stomach.

After completing the neoadjuvant treatment, surgical removal of the lung cancer will be performed.

The surgeon will remove the tumor and surrounding tissue. Tissue samples from the surgery will be sent to a laboratory to determine if all cancer cells have been eliminated and to test for specific markers called PD-L1 and TROP2.

If the pathology results show that not all cancer cells were eliminated (meaning pathological complete response was not achieved), eligibility for the next phase of the trial will be confirmed.

After surgery, a period of recovery will occur before starting the next treatment phase.

Within 28 days before starting adjuvant treatment, imaging scans will be performed. These will include a CT scan (computed tomography) or MRI (magnetic resonance imaging) of the chest, abdomen, and pelvis with contrast. These scans will confirm that no disease is detectable after surgery.

Any side effects from previous treatments must have improved to a mild level or returned to baseline before proceeding, except for certain hormone-related side effects that are being managed with hormone replacement therapy.

Once eligibility is confirmed, assignment to one of two treatment groups will occur through a process called randomization, which is similar to a coin flip.

One group will receive pembrolizumab alone, administered through intravenous infusion.

The other group will receive pembrolizumab combined with MK-2870 (also known as sacituzumab tirumotecan), both administered through intravenous infusion.

This is an open-label trial, meaning both the treating physician and the patient will know which treatment is being received.

The assigned treatment will be administered through intravenous infusion on a regular schedule. Specific dosage, frequency, and duration will be determined according to the trial protocol.

Supportive medications may continue to be provided to manage potential side effects.

Regular monitoring will occur throughout this period to assess how the treatment is being tolerated and to check for any side effects.

Regular assessments will be conducted to monitor for any signs of cancer returning. The primary measure being evaluated is disease-free survival, which means the length of time remaining free of cancer after treatment.

These assessments will be performed by both the treating physician and by independent reviewers who do not know which treatment was received (called blinded independent central review).

Additional monitoring will include assessments of overall survival, whether cancer has spread to distant parts of the body, and lung cancer-specific survival.

Quality of life will be evaluated through questionnaires that ask about physical functioning, ability to perform daily activities, breathing difficulties, coughing, and chest pain.

Any adverse events or side effects will be recorded, and any changes to treatment due to side effects will be documented.

The trial is expected to continue until October 2034, though individual participation duration may vary.