May 12, 2021: “Positive results from the Phase 3 trial investigating Sanofi and Regeneron’s PD-1 inhibitor Libtayo® (cemiplimab) in patients with recurrent or metastatic cervical cancer who had previously progressed on chemotherapy were shared today as part of a European Society for Medical Oncology (ESMO) Virtual Plenary.
Results add to previously reported data showing an improvement in overall survival (OS) with Libtayo compared to chemotherapy, and will form the basis of regulatory submissions in 2021.
“In this Phase 3 trial, Libtayo demonstrated a significant improvement in overall survival in women with advanced cervical cancer after progression on chemotherapy, reducing the risk of death by 31% compared to chemotherapy in the overall population,” said Krishnansu S. Tewari, M.D., Professor and Director of the Division of Gynecologic Oncology at the University of California, Irvine and a trial investigator.
“Improvements in progression-free survival and objective response rate were also demonstrated in the overall population compared to chemotherapy.
Taken together, this landmark trial – which enrolled patients regardless of PD-L1 expression status – helps support the use of Libtayo as a potential new second-line treatment for women with advanced cervical cancer who face a poor prognosis and limited treatment options.”
In the overall population, those treated with Libtayo (n=304) experienced significant improvements in OS, progression-free survival (PFS) and objective response rate (ORR), compared to chemotherapy (n=304), including a:
- 31% reduction in the risk of death (hazard ratio HR: 0.69; 95% confidence interval CI: 0.56-0.84; one-sided p=0.00011).
- 25% reduction in the risk of disease progression (HR: 0.75; 95% CI: 0.63-0.89; one-sided p=0.00048).
- 16% ORR (50 patients; 95% CI: 13-21%; one-sided p=0.00004), compared to 6% with chemotherapy (19 patients). Median duration of response was 16 months with Libtayo (95% CI: 12 months to not yet evaluable) and 7 months with chemotherapy (95% CI: 5-8 months), per Kaplan-Meier estimates.
In the trial, 78% of patients had advanced cervical cancer that was classified as squamous cell carcinoma (SCC).
In this patient subgroup, significant improvements were also seen with Libtayo (n=239), compared to chemotherapy (n=238), including a:
- 27% reduction in the risk of death (HR: 0.73; 95% CI: 0.58-0.91; one-sided p=0.00306).
- 29% reduction in the risk of disease progression (HR: 0.71; 95% CI: 0.58-0.86; one-sided p=0.00026).
- 18% ORR (42 patients; 95% CI: 13-23%), compared to 7% with chemotherapy (16 patients; 95% CI: 4-11%).
While assessment of the adenocarcinoma was not a pre-specified endpoint, a post-hoc analysis demonstrated the following outcomes for Libtayo-treated patients (n=65) compared to chemotherapy (n=66), including a:
- 44% reduction in the risk of death (HR: 0.56; 95% CI: 0.36-0.85; nominal one-sided p<0.005).
- 9% reduction in the risk of disease progression (HR: 0.91; 95% CI: 0.62-1.34).
- 12% ORR (8 patients; 95% CI: 6-23%), compared to 5% with chemotherapy (3 patients; 95% CI: 1-13%).
Additionally, the Phase 3 trial found Libtayo-treated patients were able to generally improve or maintain their baseline Global Health Status/Quality of Life (GHS/QOL) over time, while those treated with chemotherapy experienced a deterioration that became clinically meaningful starting at cycle 8, per the EORTC QLQ-C30 (overall estimated mean change 95% CI: improvement of 1.01 -2.033, 4.047 for Libtayo, worsening of -6.81 -10.977, -2.637 for chemotherapy; difference: 7.81; one-sided nominal p=0.00040).
No new Libtayo safety signals were observed.
Safety was assessed in patients who received at least 1 dose of study treatment: 300 patients in the Libtayo group (median duration of exposure: 15 weeks; range: 1-101 weeks) and 290 patients in the chemotherapy group (median duration of exposure: 10 weeks; range: 1-82 weeks).
Adverse events (AEs) were observed in 88% of Libtayo patients and 91% of chemotherapy patients, with those occurring in 15% or more Libtayo patients being anemia (25% Libtayo, 45% chemotherapy), nausea (18% Libtayo, 33% chemotherapy), fatigue (17% Libtayo, 16% chemotherapy), vomiting (16% Libtayo, 23% chemotherapy), decreased appetite (15% Libtayo, 16% chemotherapy) and constipation (15% Libtayo, 20% chemotherapy).
Grade 3 or higher AEs occurred in 45% of Libtayo patients and 53% of chemotherapy patients.
Among AEs in 15% or more patients, Grade 3 or higher AEs that occurred more often in the Libtayo group included asthenia (2% Libtayo, 1% chemotherapy) and pyrexia (less than 1% Libtayo, 0% chemotherapy).
Immune-related AEs were observed in 16% of Libtayo patients and less than 1% of chemotherapy patients, with 6% and less than 1% being Grade 3 or higher, respectively.
Discontinuations due to AEs occurred in 8% of Libtayo patients and 5% of chemotherapy patients.
The use of Libtayo in advanced cervical cancer is investigational and has not been fully reviewed by any regulatory authority.”
https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-12-19-35-00-2228565
