Sacituzumab Tirumotecan plus Pembrolizumab in PD-L1-Negative Advanced NSCLC.

Sacituzumab tirumotecan plus pembrolizumab significantly improved progression-free survival in PD-L1–negative advanced nonsquamous NSCLC, extending median to 15.0 vs 5.7 months.

• Why it matters: Outcomes remain suboptimal for patients with PD-L1 tumor proportion score less than 1% receiving standard first-line pembrolizumab plus chemotherapy, creating a need for better regimens.
• What they did: In a phase 3, open-label, randomized trial, 455 previously untreated patients without targetable genomic alterations were assigned 1:1 to sacituzumab tirumotecan plus pembrolizumab or chemotherapy plus pembrolizumab; progression-free survival was assessed by blinded independent central review.
• The result: After median follow-up of 9.7 months, progression-free survival was longer with sacituzumab tirumotecan plus pembrolizumab (hazard ratio 0.49; 95% CI, 0.36 to 0.65; P<0.001), with grade 3+ adverse events in 47.6% vs 60.6%.