Sacituzumab govitecan plus pembrolizumab fails to improve progression‑free survival in PD‑L1‑high metastatic NSCLC

The phase 3 EVOKE‑03/KEYNOTE‑D46 trial, presented at the International Association for the Study of Lung Cancer 2026 World Conference on Lung Cancer, found that adding sacituzumab govitecan (SG) to pembrolizumab did not produce a statistically significant improvement in progression‑free survival compared with pembrolizumab alone when used as first‑line therapy for patients with metastatic non‑small cell lung cancer (NSCLC) whose tumors express a PD‑L1 tumor proportion score of 50 % or higher. The study enrolled participants with advanced NSCLC and evaluated progression‑free survival as the primary endpoint, concluding that the combination therapy failed to meet the prespecified threshold for benefit over pembrolizumab monotherapy.

Sacituzumab govitecan, an antibody‑drug conjugate targeting Trop‑2, has shown activity in several solid tumors, while pembrolizumab is an established PD‑1 inhibitor used in frontline NSCLC treatment. The EVOKE‑03/KEYNOTE‑D46 results suggest that, despite the mechanistic rationale for combining a Trop‑2‑directed agent with immune checkpoint inhibition, this regimen does not enhance early disease control in the defined high‑PD‑L1 population. Researchers will likely focus on alternative combinations or patient subsets in future studies to determine the optimal use of SG in lung cancer therapy.