Libtayo (Cemiplimab): First Immune Therapy Demonstrating Significant Improvement in Overall Survival for Recurrent or Metastatic Cervical Cancer

May 13, 2021 /BioValleyBIOON/ -- Sanofi and its partner Regeneron recently in EuropeTumorVirtual Plenary Session of the Society of Internal MedicineConference(ESMO Virtual Plenary) presented the Phase 3 trial of anti-PD-1 therapy Libtayo (cemiplimab) for cervical cancerClinical Trialpositive results. The trial was conducted in patients with recurrent or metastatic cervical cancer who had previously received chemotherapy, regardless of PD-L1 expression status. The results presented at this conference supplement previously reported data, demonstrating that Libtayo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared with chemotherapy. Furthermore, Libtayo showed a statistically significant advantage over chemotherapy in patient-reported outcomes (PROs). These data will form the basis for the regulatory submission in 2021.

It is worth noting that,Libtayo is the first immunotherapy demonstrated to significantly improve OS, PFS, and ORR in patients with cervical cancer: Compared with chemotherapy, the31% Reduction in Mortality Risk(HR=0.69, one-sided p=0.00011), will25% Reduction in the Risk of Disease Progression(HR = 0.75, one-sided p = 0.00048), andSignificant Improvement in ORR(16% vs 6%; one-sided p=0.00004). To date, Libtayo has yielded positive pivotal data in four cancer types. Previously, Libtayo also achieved first-in-class pivotal results in the treatment of advanced basal cell carcinoma (BCC) and advanced cutaneous squamous cell carcinoma (CSCC).

Recurrent or metastatic cervical cancer is notoriously difficult to treat, and there is no approved standard-of-care regimen after first-line chemotherapy. In this trial, enrolled patients, regardless ofTumorPD-L1 Status. Results confirmed that Libtayo demonstrated significant efficacy compared with chemotherapy.

The investigator of the trial, a gynecologist at the University of CaliforniaTumorProfessor and Department Chair Krishnansu S. Tewari stated, “In this Phase 3Clinical TrialIn the treatment of patients with recurrent or metastatic cervical cancer who had previously received platinum-based chemotherapy, Libtayo reduced the risk of death by 31% compared with chemotherapy in the overall study population. Furthermore, Libtayo demonstrated significant improvements in progression-free survival (PFS) and objective response rate (ORR) compared with chemotherapy in the overall study population. This landmark clinical achievement supports the use of Libtayo as a new second-line treatment for women with advanced cervical cancer who have a poor prognosis and limited treatment options.”

This is the largest phase 3 randomized trial conducted in the treatment of advanced cervical cancerClinical Trial, a total of female patients from 14 countries worldwide were enrolled (median age: 51 years). These patients were randomized to receive either Libtayo monotherapy (350 mg every 3 weeks) or investigator-selected standard chemotherapy regimens (pemetrexed, vinorelbine, topotecan, irinotecan, or gemcitabine). Compared with the chemotherapy group, patients in the Libtayo group experienced:

—In the entire study population:（1）The risk of death was reduced by 31%., the median overall survival was 12.0 months in the Libtayo group (n=304) versus 8.5 months in the chemotherapy group (n=305), with a statistically significant difference (HR=0.69; 95% CI: 0.56–0.84; one-sided p=0.00011). (2) The risk of disease progression was reduced by 25% (HR=0.75; 95% CI: 0.63–0.89; one-sided p=0.00048). (3) The objective response rate (ORR) was significantly higher (16% vs. 6%; p=0.00004), and the median duration of response (DOR) was significantly longer (16 months vs. 7 months).

—In the squamous cell carcinoma population:（1）27% Reduction in Mortality Risk, the median overall survival was 11.1 months in the Libtayo group (n=239) versus 8.8 months in the chemotherapy group (n=238), with a statistically significant difference (HR=0.73; 95% CI: 0.58–0.91; one-sided p=0.00306). (2) The risk of disease progression was reduced by 29% (HR=0.71; 95% CI: 0.58–0.86; one-sided p=0.00026). (3) The objective response rate (ORR) was improved (18% vs. 7%).

——In the adenocarcinoma population:（1）44% Reduction in Mortality Risk, the median overall survival was 13.3 months in the Libtayo group (n=65) versus 7.0 months in the chemotherapy group (n=66), with a statistically significant difference (HR=0.56; 95% CI: 0.36-0.85; nominal one-sided p<0.005). (2) The risk of disease progression was reduced by 9% (HR=0.91; 95% CI: 0.62-1.34). (3) The ORR was improved (12% vs 5%).

——Health Status/Quality of Life:Patients Treated with LibtayoOver time, overall global health status/quality of life (GHS/QOL) can be improved or maintained at baseline levels., whereas patients receiving chemotherapy experienced a clinically meaningful deterioration starting from Cycle 8, based on the EORTC QLQ-C30 (overall estimated mean change 95% CI: Libtayo improvement 1.01 [-2.033, 4.047], chemotherapy deterioration -6.81 [-10.977, -2.637]; difference = 7.81; one-sided nominal p = 0.00040).

—No new safety signals for Libtayo were observed in this trial. Adverse events occurred in 88% of patients in the Libtayo treatment group and 91% of patients in the chemotherapy group, with serious adverse events reported in 30% and 27% of patients, respectively.

Cervical cancer is the fourth leading cause of cancer-related deaths among women worldwide, with women aged 35–44 years being most frequently diagnosed. Nearly all cases are caused by human papillomavirus (HPV) infection; approximately 80% are classified as squamous cell carcinomas (originating from cells at the base of the cervix), while the majority of the remaining cases are adenocarcinomas (originating from glandular cells in the upper part of the cervix). Cervical cancer is often curable when detected early and treated effectively, but treatment options for advanced-stage disease are more limited. It is estimated that approximately 570,000 women worldwide areDiagnosisCervical Cancer. In the United States, there are 14,500 new diagnoses annually, with approximately 4,000 deaths each year.

Libtayo is an anti-PD-(L)1 inhibitor, a class of cancer immunotherapies that has garnered significant attention. It aims to harness the body’s own immune system to combat cancer by blocking the PD-1/PD-L1 signaling pathway, thereby inducing cancer cell death, and is effective in treating various typesTumorpotential. Libtayo is a fully human monoclonal antibody that targets the immune checkpoint receptor PD-1 on T cells. By binding to PD-1, Libtayo has been shown to prevent cancer cells from inhibiting T cell activation via the PD-1 pathway.

Previously, Libtayo had been approved for the treatment of patients with advanced stages of the two most common types of skin cancer: (1) Libtayo was the first drug approved for the treatment of advanced cutaneous squamous cell carcinoma (CSCC), indicated for patients with metastatic CSCC and those with locally advanced CSCC who are not candidates for curative surgery or curative radiation therapy; (2) Libtayo was the first immunotherapy approved for the treatment of advanced basal cell carcinoma (BCC), indicated for patients with advanced BCC who have previously been treated with a hedgehog pathway inhibitor (HHI) or who are not suitable candidates for such therapy.

In February 2021, Libtayo received U.S.FDAApproval of the third indication: for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors highly express PD-L1 (Tumor Proportion Score [TPS] ≥50%), specifically: tumors with high PD-L1 expression (TPS ≥50%), metastatic or locally advanced disease, and not suitable for surgical resection or curative chemoradiotherapy.TumorNSCLC patients without EGFR, ALK, or ROS1 alterations.

Libtayo was created and optimized using Regeneron’s proprietary VelocImmune technology platform and is currently being co-developed under the global collaboration agreement between Regeneron and Sanofi for the treatment of various types of cancer. Libtayo’s extensive clinical program focuses on refractory cancers, including skin cancer, cervical cancer, solid tumors, and hematologic malignancies. (Bioon.com)

Original Source: Positive Phase 3 Libtayo® (cemiplimab) Results in Advanced Cervical Cancer Presented at ESMO Virtual Plenary