Regeneron UK Limited has reported five-year follow-up results from the Phase 3 Empower-lung 3 trial, evaluating cemiplimab plus platinum-based chemotherapy versus chemotherapy alone as first-line treatment for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) without EGFR, ALK or ROS1 aberrations.

The primary endpoint was overall survival, with secondary endpoints including progression-free survival, objective response rate and duration of response. Data were presented in a mini-oral session at the IASLC 2025 World Conference on Lung Cancer (WCLC).

After a median follow-up of 60.9 months, cemiplimab plus chemotherapy (n=312) showed a median overall survival of 21.1 months versus 12.9 months for chemotherapy alone (n=154; hazard ratio 0.66; 95% confidence interval 0.53–0.83). The five-year overall survival probability was 19.4% for the combination versus 8.8% for chemotherapy. Median progression-free survival was 8.2 months versus 5.5 months (hazard ratio 0.58; 95% CI 0.47–0.72), and the objective response rate was 43.6% versus 22.1%, including complete responses of 6.4% versus 0%. Duration of response was 16.4 months versus 7.3 months.

Exploratory subgroup analyses demonstrated consistent benefits across histologies and PD-L1 expression:

• Patients with squamous histology: median OS 22.3 months versus 13.8 months (HR 0.68; 95% CI 0.49–0.94)

• Patients with non-squamous histology: median OS 19.4 months versus 12.4 months (HR 0.62; 95% CI 0.46–0.82)

• Patients with PD-L1 ≥1%: median OS 24.0 months versus 12.1 months (HR 0.54; 95% CI 0.41–0.70)

The safety profile at five years remained consistent with previous reports. Median exposure was 38.8 weeks for cemiplimab plus chemotherapy and 21.3 weeks for chemotherapy alone. Adverse events of any grade occurred in 96.5% of cemiplimab patients (49.4% Grade ≥3) and 94.8% of chemotherapy patients (32.7% Grade ≥3). Treatment-related Grade ≥3 events occurred in 30.1% of cemiplimab patients, leading to permanent discontinuation in 4.5% and death in 1.3%, compared with 18.3%, 1.3% and 0.7% in the chemotherapy group.

The Empower-lung 3 trial enrolled 466 patients with locally advanced or metastatic NSCLC across squamous and non-squamous histologies and all PD-L1 expression levels, excluding those with ALK, EGFR or ROS1 aberrations. Patients were randomised 2:1 to receive cemiplimab 350 mg every three weeks plus platinum-doublet chemotherapy for four cycles, or chemotherapy alone. Notably, the trial included patients considered difficult to treat: 43% had squamous histology, 67% had PD-L1 <50%, 15% had inoperable locally advanced disease not eligible for definitive chemoradiation, 7% had pretreated brain metastases, and 84% had ECOG performance status of 1.