PD-L1 vs LAG-3 Expression in Non–Small Cell Lung Cancer

The phase 2 RELATIVITY-104 study (NCT04623775) aimed to evaluate the effectiveness of a combination therapy involving nivolumab and relatlimab (Odualag), and platinum doublet chemotherapy as a first-line treatment for metastatic non–small cell lung cancer (NSCLC).

Relatlimab is a human LAG-3 blocking antibody, and nivolumab is a PD-1 blocking antibody. Previous studies have shown that targeting immune checkpoints like PD-1 and LAG-3 can improve outcomes in certain cancers.

Patients with previously untreated stage IV/recurrent NSCLC were randomized to receive either nivolumab, relatlimab, and chemotherapy or nivolumab and chemotherapy alone. The primary end point was overall response rate (ORR).

The combination therapy of nivolumab, relatlimab, and chemotherapy showed a higher ORR compared to nivolumab and chemotherapy alone, especially in patients with PD-L1 expression ≥ 1% and nonsquamous histology. The median duration of response was also longer with the combination therapy. However, the overall survival data were immature at the time of the analysis. The safety profile of the combination therapy was manageable, with similar rates of adverse events to the control group.

The results of the RELATIVITY-104 study suggest that the combination of nivolumab and relatlimab may be a promising treatment option for patients with metastatic NSCLC, particularly those with PD-L1 expression ≥ 1% and nonsquamous histology. Further studies are needed to confirm these findings and evaluate the long-term benefits of this combination therapy.

Here, Nicolas Girard, MD, PhD, thoracic oncologist at Institut Curie in Paris, France, discusses the targets of PD-L1 and LAG-3.

Transcription:

0:05 | PD-L1 is a strong predictor for the efficacy of anti–PD-1 and anti–PD-L1 agents. And in this study, more than 50% of patients had positive PD-L1expression. So that's very clear. For LAG-3, it is very interesting to see that LAG-3 expression is a coexpression with PD-L1 at the same time on a tumor cell surface. And LAG-3 works with PD-1.

0:35 | So at the end, the inhibition of LAG-3 and PD-1 are working together to improve antitumor responses. This combination is approved in melanoma, in advanced melanoma, nivolumab plus relatlimab. So at the end, the LAG-3 biomarker is probably working with PD-L1 expression, and the driver for the efficacy remains PD-L1.