September 19, 2021: “Positive Phase 3 results for Sanofi and Regeneron Pharmaceuticals, Inc.’s Libtayo® (cemiplimab) combination treatment were presented during a late-breaking session at the European Society for Medical Oncology Virtual Congress 2021.
The trial, which met its primary overall survival (OS) endpoint and all key secondary endpoints, assessed the investigational use of PD-1 inhibitor Libtayo in combination with a physician’s choice of platinum-doublet chemotherapy (Libtayo combination) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) irrespective of histology and across all PD-L1 expression levels, compared to chemotherapy alone.
These results were also achieved in a patient population with varied baseline characteristics and will form the basis of regulatory submissions, including in the U.S. and European Union (EU).
“Libtayo added to chemotherapy significantly improved patient outcomes, extending median overall survival to 22 months and median progression-free survival to 8 months,” said Miranda Gogishvili, M.D., an oncologist at the High Technology Medical Center University Clinic, in Tbilisi, Georgia and a trial investigator.
“Exploratory analyses showed that survival improvements were seen across squamous and non-squamous histologies and in patients with reduced daily functioning, with 43% of patients having squamous disease and 84% having an ECOG 1 performance status.
Furthermore, in another exploratory analysis, the Libtayo combination helped delay deterioration in patient-reported quality of life and pain symptoms.”
In the overall population, patients treated with the Libtayo combination (n=312) experienced significant improvements compared to those receiving chemotherapy alone (n=154), including a:
- 22-month median OS compared to 13 months for chemotherapy, representing a 29% relative reduction in the risk of death (hazard ratio HR: 0.71; 95% confidence interval CI: 0.53 to 0.93; p=0.014). The 12-month probability of survival was 66% for the Libtayo combination and 56% for chemotherapy.
- 8-month median progression-free survival (PFS) compared to 5 months for chemotherapy, representing a 46% relative reduction in the risk of disease progression (HR: 0.56; 95% CI: 0.44 to 0.70; p<0.0001). The 12-month probability of PFS was 38% for the Libtayo combination and 16% for chemotherapy.
- 43% objective response rate (ORR) compared to 23% for chemotherapy.
- 16-month median duration of response (DOR) compared to 7 months for chemotherapy.
Favorable patient-reported outcomes were also observed. Specifically, the Libtayo combination delayed deterioration in pain symptoms (HR: 0.39; 95% CI: 0.26 to 0.60; nominal p<0.0001) and showed a trend towards delayed deterioration in global health status/quality of life (HR: 0.78; 95% CI: 0.51 to 1.19; nominal p=0.248), compared to chemotherapy. The Libtayo combination also improved pain symptoms, compared to chemotherapy (-4.98 difference in baseline changes between treatment groups; 95% CI: -8.36 to -1.60; nominal p=0.004).
No new Libtayo safety signals were identified. The median duration of exposure was 38 weeks for the Libtayo combination (n=312) and 21 weeks for chemotherapy (n=153). Adverse events (AEs) of any grade occurred in 96% of patients receiving the Libtayo combination and 94% of patients receiving chemotherapy alone, with 19% and 0% being immune-mediated, respectively.
For the Libtayo combination and chemotherapy groups, the most common AEs were anemia (44%, 40%), alopecia (37%, 43%) and nausea (25%, 16%); grade ≥3 AEs occurring in ≥5% of patients were anemia (10%, 7%) and neutropenia (both 6%).
Treatment discontinuation due to AEs occurred in 5% of patients receiving the Libtayo combination and 3% receiving chemotherapy.
“These data add to the growing body of evidence supporting the use of Libtayo in patients with advanced non-small cell lung cancer,” said Peter C. Adamson, M.D., Global Development Head, Oncology and Pediatric Innovation at Sanofi.
“With additional trials underway investigating Libtayo as the backbone in combinations with conventional and novel therapeutic approaches, we are encouraged by the potential to further improve outcomes for patients with difficult-to-treat cancers.”
Lung cancer is the leading cause of cancer death worldwide.
In 2020, an estimated 2.2 million and 225,000 new cases were diagnosed globally and in the U.S., respectively. Approximately 84% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages. While PD-1 inhibitor monotherapy has primarily advanced the treatment of NSCLC with ≥50% PD-L1 expression, approximately 70% of all NSCLC cases will have <50% PD-L1 expression, making it the most common treatment setting.
“This Phase 3 trial was stopped early because Libtayo significantly improved overall survival compared to chemotherapy, a milestone also achieved by our Phase 3 trial for Libtayo monotherapy as a first-line treatment for advanced non-small cell lung cancer with high PD-L1 expression,” said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron.
“Both trials were designed to reflect everyday clinical practice by allowing for the enrollment of patients with difficult-to-treat disease characteristics.
And this is the second Libtayo trial to demonstrate significant improvement in its primary and key secondary endpoints for these patient populations, compared to chemotherapy.”
The use of Libtayo in combination with chemotherapy for advanced NSCLC is investigational, and its safety and efficacy have not been fully evaluated by any regulatory authority.”
https://www.sanofi.com/en/media-room/press-releases/2021/2021-09-19-17-30-00-2299392
