Metastatic Lung Cancer Trial Misses Survival Endpoint with ADC Combo
In a large randomized trial, adding sacituzumab govitecan to pembrolizumab did not significantly improve progression-free survival or overall survival in patients with metastatic non-small cell lung cancer selected for PD-L1 positivity. The combination showed a numerical improvement in progression-free survival but failed to meet statistical significance, and overall survival was slightly worse in the combination arm. Safety analysis showed more adverse events with the combination.
The EVOKE-03 trial enrolled patients with untreated metastatic non-small cell lung cancer whose tumors expressed PD-L1 at a total positive score of 50% or higher, a population already known to respond well to pembrolizumab alone. The phase II predecessor, EVOKE-02, had reported a 66.7% objective response rate in just 30 patients, but the larger phase III study saw that figure drop to 55.6% — a 12% absolute improvement over monotherapy, roughly matching what chemotherapy typically adds.
The discussant noted that pembrolizumab's established 44.8% response rate from the KEYNOTE-024 trial set a high benchmark, and the small phase II sample may have led to overestimating the ADC's potential benefit. Median duration of response was similar between arms, suggesting the ADC's effect resembles chemotherapy — converting non-responders into short-term responders without producing a durable survival advantage.
For patients with PD-L1-high metastatic NSCLC, this trial reinforces that pembrolizumab monotherapy remains a valid standard, while also tempering enthusiasm for combining ADCs with immunotherapy in this setting. The modest PFS gain without survival benefit, plus added toxicity, could influence treatment decisions and insurance coverage considerations. Future research may shift toward better biomarker selection and overall survival as the primary measure, potentially reshaping how drug combinations are evaluated and which patients are offered experimental regimens.