On September 9, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported five-year results from the final pre-specified overall survival (OS) analysis of the Phase 3 EMPOWER-Lung 1 trial, which evaluated Libtayo (cemiplimab) monotherapy versus chemotherapy as a first-line treatment for adults with advanced non-small cell lung cancer (NSCLC) with ≥50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations (Press release, Regeneron, SEP 9, 2024, View Source [SID1234646440]). The late-breaking results will be presented in an oral session at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer.

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"The five-year results from EMPOWER-Lung 1 showcase the durable survival benefit and impressive efficacy of first-line Libtayo monotherapy compared to chemotherapy in patients with PD-L1 high, advanced NSCLC, including a direct correlation between survival benefits and PD-L1 expression level," says Ana Baramidze, MD, PhD, Head of Clinical Research Department at Todua Clinic, Tbilisi, Georgia. "Furthermore, EMPOWER-Lung 1 continues to offer important new data to help doctors increase their understanding of investigational treatment strategies for patients who progress on PD-1 inhibitor monotherapy. For instance, EMPOWER-Lung 1 was one of the few trials to evaluate survival when adding chemotherapy to a PD-1 inhibitor following progression."

At the five-year follow-up, Libtayo remained superior to chemotherapy in the population of patients confirmed to have ≥50% PD-L1 expression (using an FDA approved assay), demonstrating continued and clinically meaningful benefits consistent with the prior 1-year analysis in this study population (as previously published in The Lancet and also as previously provided in the approved label for the FDA-approved assay):

1-year Analysis 5-year Analysis
Libtayo
(n=283) Chemotherapy
(n=280) Libtayo
(n=284) Chemotherapy
(n=281)
Overall survival (OS)
Mediana not reached 14 months 26 months 13 months
Hazard ratio (HR)
(95% confidence
interval [CI]; p-value)b 0.57
(0.42 to 0.77; p=0.0002) 0.59
(0.48 to 0.72; p<0.0001)
Progression-free survival (PFS)
Mediana 8 months 6 months 8 months 5 months
HR (95% CI; p-value)b 0.54
(0.43 to 0.68; p<0.0001) 0.50
(0.41 to 0.61; p<0.0001)
Objective response
rate (ORR) 39% 20% 46.5% 21%
Median duration of
response (DoR) 17 months 6 months 24 months 6 months
NOTE: The analysis was conducted in a subset of the randomized population that excluded 147 patients whose tumors could not be retested or were later found to have <50% PD-L1 expression.
a Based on Kaplan-Meier method
b Based on stratified proportional hazards model

Continued and clinically meaningful benefits were also observed at this five-year follow-up of the overall trial population (in which not all patients were confirmed to have ≥50% PD-L1 expression), as compared to the prior 1-year analysis in this population.

1-year Analysis 5-year Analysis
Libtayo
(n=356) Chemotherapy
(n=354) Libtayo
(n=357) Chemotherapy
(n=355)
OS
Mediana 22 months 14 months 23 months 14 months
HR (95% CI; p-value)b 0.68
(0.53 to 0.87; p=0.0022) 0.64
(0.54 to 0.77; p<0.0001)
PFS
Mediana 6 months 6 months 6 months 5 months
HR (95% CI; p-value)b 0.59
(0.49 to 0.72; p<0.0001) 0.55
(0.46 to 0.66; p<0.0001)
ORR 37% 21% 42% 21%
Median DoR 21 months 6 months 24 months 6 months
a Based on Kaplan-Meier method
b Based on stratified proportional hazards model

Importantly, EMPOWER-Lung 1 allowed patients who experienced disease progression to change their therapy, with those assigned to Libtayo having the option to add four cycles of chemotherapy. Among these patients (n=75), the addition of chemotherapy was associated with a 15-month median OS (95% CI: 11 to 18 months), 7-month median PFS (95% CI: 6 to 8 months) and 28% ORR (95% CI: 18% to 40%).

The exploratory subgroup analysis of EMPOWER-Lung 1 also showed direct correlations between survival and disease progression benefits and PD-L1 expression level among Libtayo patients, supporting the direct correlation between tumor response and PD-L1 expression level previously observed. At five years, those with tumor PD-L1 expression of ≥90% (n=99) derived the greatest benefit with a median OS of 39 months (95% CI: 23 months to not evaluable) and a 15-month median PFS (95% CI: 10 to 21 months). These correlations with PD-L1 expression level were not observed with chemotherapy.

No new safety signals were observed at five years among evaluable patients (Libtayo=356; chemotherapy=343), following a median duration of exposure of 36 weeks to Libtayo and 18 weeks to chemotherapy. Adverse events (AEs) of any grade occurred in 93% of Libtayo patients (46% ≥Grade 3) and 96% of chemotherapy patients (52% ≥Grade 3). The most common AEs occurring in at least 10% of Libtayo patients included anemia (20%), decreased appetite (14%), fatigue (14%), pneumonia (12%), arthralgia (12%), back pain (12%), dyspnea (11%), cough (10%) and pruritus (10%). Among Libtayo patients, AEs were serious in 36% and led to permanent discontinuation in 9% and death in 10%, compared to 29%, 5% and 10% in the chemotherapy arm, respectively.

Among the 75 Libtayo patients who received additive chemotherapy after disease progression, AEs of any grade occurred in 89% (36% ≥Grade 3), following a median duration of exposure of 27 weeks to Libtayo. The most common AEs included anemia (35%), alopecia (24%), diarrhea (21%), nausea (20%), neutropenia (15%) and asthenia (11%). AEs were serious in 27% of patients and led to discontinuation of treatment in 5% of patients and death in 4% of patients.

Additional presentations on data from Regeneron’s oncology portfolio and pipeline are being shared at WCLC.

The potential use of adding chemotherapy to Libtayo following disease progression as described above is investigational, and the safety and efficacy of this regimen have not been fully evaluated by any regulatory authority.