Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial.
Summary
In an interim analysis of a phase 3 RCT (n=413), sacituzumab tirumotecan plus pembrolizumab significantly prolonged PFS versus pembrolizumab alone (NR vs 5.7 months; HR 0.35), with benefit across PD-L1 subgroups. Grade ≥3 AEs were more frequent with the combination (55% vs 31%).
Key Findings
- Median PFS was not reached with sacituzumab tirumotecan plus pembrolizumab vs 5.7 months with pembrolizumab alone (HR 0.35; p<0.0001).
- Consistent PFS benefit across PD-L1 TPS 1–49% (HR 0.28) and ≥50% (HR 0.47) subgroups.
- Grade ≥3 treatment-emergent adverse events occurred in 55% vs 31% with combination vs monotherapy.
Clinical Implications
For driver-negative, PD-L1 TPS ≥1% advanced NSCLC, ADC–IO may become a frontline option pending mature OS, safety, and quality-of-life data; clinicians should prepare for toxicity monitoring and management of higher-grade adverse events.
Why It Matters
This trial provides compelling phase 3 evidence that an ADC–IO combination can redefine first-line therapy for PD-L1–positive advanced NSCLC without targetable alterations.
Limitations
- Open-label design may introduce performance or detection biases despite BICR.
- Interim analysis with immature OS and limited long-term safety/QoL data.
Future Directions
Await mature overall survival, durability of response, and patient-reported outcomes; explore biomarkers for ADC–IO synergy and optimize toxicity mitigation strategies.
Study Information
- Study Type
- RCT
- Research Domain
- Treatment
- Evidence Level
- I - Phase 3 randomized controlled trial with blinded central review of PFS.
- Study Design
- OTHER