Comparison of Two Immunotherapies as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer with High PD-L1 Expression

In stage 4 non-small-cell lung cancer, the tumor has already spread beyond the lung and, as a rule, can no longer be completely cured. The protein PD-L1 plays a role in this. It is found on the surface of some tumor cells and acts as what is known as an immune checkpoint. Through PD-L1, tumor cells can inhibit the immune system’s defense cells (T cells), causing them to attack the tumor less vigorously. This is precisely where so-called immunotherapies come into play. Pembrolizumab is an already approved antibody that binds to the PD-1 receptor, thereby blocking the PD-1/PD-L1 signaling pathway. This signaling pathway normally acts as a brake on the immune system, and blocking it allows the body’s own immune cells to better recognize and fight cancer cells again. Rilvegostomig is a bispecific antibody that has not yet been approved; it binds simultaneously to the immune checkpoint receptors PD-1 and TIGIT on T cells and is thus intended to strengthen the body’s own defense against tumor cells.

The goal of this Phase 3 study is to compare two immunotherapies, rilvegostomig and pembrolizumab, as first-line monotherapies for metastatic non-small cell lung cancer with high PD-L1 expression. Patients will be randomly assigned to two treatment groups and will receive either rilvegostomig (study arm) or pembrolizumab (control arm) every three weeks as an intravenous infusion. The study is double-blind, which means that neither the patients nor the study physicians know who is receiving which of the two drugs. The main objectives (primary endpoints) of the study are overall survival and progression-free survival (time without disease progression) for up to five years.

Eligible participants include women and men aged 18 and older with metastatic non-small cell lung cancer (Stage 4) that is no longer curable and has a high PD-L1 expression. Participants must not have any sensitizing mutations in the EGFR gene, any rearrangements of the ALK and ROS1 genes, or any other treatable genetic driver mutations for which approved targeted first-line treatments already exist. The disease must not have been previously treated with any therapy for advanced lung cancer.