SAKK 18/24 Treatment of patients with advanced lung cancer (metastatic non-small cell lung cancer) with a dose-reduced chemotherapy plus Cemiplimab or with Cemiplimab alone; treatment is given to individuals who have not yet received therapy for lung cancer, who are older and frail, and whose lung cancer has certain characteristics (PD-L1 less than 50%).

Metastatic non-small cell lung cancer is often treated with a combination of chemotherapy and immunotherapy. Among patients over 70 years old, some are already health-compromised and frail, requiring assistance in daily life. Older and/or frail individuals often do not tolerate standard-dose chemotherapy well, and the risk of side effects is greater for them than for younger individuals.

Therefore, the SAKK 18/24 study investigates how effective and safe chemotherapy is for patients over 70 years old when the chemotherapy drugs are administered at lower doses than usual. The aim of the study is to find a potentially effective and simultaneously well-tolerated therapy for older people with metastatic non-small cell lung cancer.

Disease under investigation

Non-small cell lung cancer that has already formed metastases (secondary tumors in other organs) in individuals who are at least 70 years old.

Intervention under investigation

Participants in the study will be randomly assigned to one of two groups.

• Group 1 (Intervention group): Treatment with dose-reduced chemotherapy (two active substances) and the active substance Cemiplimab (immunotherapy) for 12 weeks. The medications will be administered as an infusion. The frequency of administration depends on the characteristics of the tumor tissue. After the completion of the 12 weeks of combination treatment with chemotherapy, an infusion of Cemiplimab will be given every three weeks for a maximum of two years from the start of therapy.
• Group 2 (Control group): Treatment with the active substance Cemiplimab alone, with the addition of dose-reduced chemotherapy only if the immunotherapy alone is not sufficiently effective. The infusion of Cemiplimab will be given every three weeks for a maximum of two years.

The results obtained in both groups will be compared.

Criteria for participation in trial
Individuals participating in the study must meet various criteria. The most important include:

• Age: at least 70 years.
• The participating individual cannot undergo chemotherapy with the usual dosage, for example, due to age or health condition.
• Tests have shown that less than half of the tumor cells in the participating individual's tumor tissue produce a protein called 'PD-L1'. This protein prevents the body's immune system from attacking and destroying the tumor cells.

Exclusion criteria
Not all individuals with metastatic non-small cell lung cancer can participate in the study. The main criteria that may lead to someone being excluded from the study include:

• The metastatic lung cancer has already been treated with medications.
• Tests have shown that certain genetic changes are present in the tumor cells. Tumors with such changes can be treated with other substances than the study medications.
• The tumor is so large or has spread in the body so much that there is a risk of rapid disease progression.