Regeneron and Sanofi announced that the Phase 3 trial of Libtayo (cemiplimab) monotherapy in patients with recurrent or metastatic cervical cancer was stopped early due to positive overall survival (OS) results. The trial demonstrated a statistically significant and clinically meaningful improvement in OS compared to chemotherapy in patients who had previously been treated with chemotherapy. This marks Libtayo as the first immunotherapy to demonstrate improved overall survival in this patient population.
The Phase 3 trial enrolled women with recurrent or metastatic cervical cancer, regardless of their PD-L1 status. Patients were randomized to receive Libtayo monotherapy (350 mg every 3 weeks) or an investigator's choice of commonly used chemotherapy regimens. The primary endpoint of the trial was OS, analyzed first among patients with squamous cell carcinoma and then in the total population.
Significant Survival Improvement
The results showed that Libtayo monotherapy reduced the risk of death by 31% compared to chemotherapy in the total population (HR: 0.69; 95% CI: 0.56-0.84; p<0.001). The median overall survival was 12.0 months for patients receiving Libtayo compared to 8.5 months for those receiving chemotherapy. In patients with squamous cell carcinoma, Libtayo reduced the risk of death by 27% (HR: 0.73; 95% CI: 0.58-0.91; p=0.003), with median survival of 11.1 months versus 8.8 months for chemotherapy. Adenocarcinoma patients experienced a 44% reduction in the risk of death (HR: 0.56; 95% CI: 0.36-0.85; p<0.005), with median survival of 13.3 months versus 7.0 months for chemotherapy.
Safety Profile
No new Libtayo safety signals were observed in the trial. Adverse events (AEs) were observed in 88% of Libtayo patients and 91% of chemotherapy patients, with serious AEs occurring in 30% and 27%, respectively. The most common AEs in the Libtayo group included anemia (25%), nausea (18%), and fatigue (17%). Discontinuations due to AEs occurred in 8% of Libtayo patients and 5% of chemotherapy patients.
Clinical Significance
"Libtayo monotherapy is the first medicine to demonstrate an improvement in overall survival in women with recurrent or metastatic cervical cancer following progression on platinum-based chemotherapy in a Phase 3 trial," 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. "This landmark clinical achievement will bring hope to women with advanced cervical cancer who are often younger than patients with other cancers."
Regulatory Plans
Regeneron and Sanofi plan to submit the data from this trial to regulatory authorities in 2021. Libtayo is already approved for certain patients with advanced cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC), and non-small cell lung cancer (NSCLC) in the United States.
About Cervical Cancer
Cervical cancer is the fourth leading cause of cancer death in women worldwide, with approximately 570,000 new cases diagnosed each year. The majority of cases are caused by human papillomavirus (HPV) infection. While cervical cancer is often curable when detected early, treatment options are limited in advanced stages, highlighting the unmet need for effective therapies in this setting.
