Cemiplimab Impresses in a Phase 3 Trial of Cervical Cancer, Regulatory Submission Expected


Promising overall survival results lead to an early stop to a phase 3 trial of cemiplimab versus chemotherapy in relapsed/refractory cervical cancer, according to the drug’s developer.

A phase 3 trial of cemiplimab (Libtayo) versus chemotherapy in patients with previously treated metastatic cervical cancer was stopped early based on positive results demonstrating overall survival (OS) superiority of the experimental regimen, according to Sanofi and Regeneron who are responsible for developing the PD-1 inhibitor.

Treatment with cemiplimab (n = 304) reduce the risk of death by 31% compared with chemotherapy (n = 304), with a median OS of 12.0 months versus 8.5 months, respectively (HR, 0.69; 95% CI, 0.56-0.84; P <.0001).

“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,” Krishnansu S. Tewari, MD, professor and director of the Division of Gynecologic Oncology at the University of California, Irvine and a trial investigator, said in a press release. “This landmark clinical achievement will bring hope to women with advanced cervical cancer who are often younger than patients with other cancers. This is reflected in the trial where the average age was 51.”\

Breaking down the patient population by histology, those with squamous cell carcinoma saw a 27% reduction in the risk of death when treated with cemiplimab, with a median OS of 11.1 months versus 8.8 months with chemotherapy (HR, 0.73; 95% CI, 0.58-0.91; P = .003). In those with adenocarcinoma, the median OS for cemiplimab and chemotherapy were 13.3 months and 7.0 months, respectively, equating to a 44% reduction in the risk of death (HR, 0.56; 95% CI, 0.36-0.85; P <.005).

No new safety signals with cemiplimab were noted. The safety population was comprised of 300 patients receiving cemiplimab and 290 on chemotherapy, with median treatment exposure lasting 15 weeks (range, 1-101) and 10 weeks (range, 1-82), respectively. Adverse events (AEs) were observed in 88% of patients in the cemiplimab group and 91% on chemotherapy; serious AEs were noted in 30% and 27%, respectively. Most common AEs include anemia (25% vs 45%, respectively), nausea (18% vs 33%), fatigue (17% vs 16%), vomiting (16% vs 23%), and constipation (15% vs 20%). Discontinuations as a result of AEs occurred in 8% of the cemiplimab group and 5% of the chemotherapy group.

Patients treated on the trial had recurrent or metastatic cervical cancer that had progressed on platinum-based chemotherapy. The patient population was comprised of 78% squamous cell carcinoma and 22% adenocarcinoma, and the median patient age was 51 years. OS was the primary end point of the trial, analyzed first in the squamous cell population.

Patients receiving cemiplimab monotherapy had treatment at a dose of 350 mg every 3 weeks and those receiving chemotherapy had investigator’s choice of either pemetrexed, vinorelbine, topotecan, irinotecan, or gemcitabine.

“Recurrent or metastatic cervical cancer is notoriously difficult to treat and has no approved standard of care after first-line chemotherapy,” Israel Lowy, MD, PhD, senior vice president of Translational and Clinical Sciences, Oncology, at Regeneron, said in a press release. “This trial, which enrolled patients regardless of their PD-L1 status, demonstrated that Libtayo helped patients with recurrent or metastatic cervical cancer live longer after progression on prior chemotherapy. This is the fourth patient population in which Libtayo has shown clinical benefit and we look forward to submitting the results to regulatory authorities later this year.”

This decision was aided by a unanimous recommendation from the Independent Data Monitoring Committee (IDMC). These data will serve as the basis for regulatory submission of a cervical cancer indication for cemiplimab in 2021.


Phase 3 trial of Libtayo (cemiplimab) monotherapy in advanced cervical cancer stopped early for positive result on overall survival. News release. Sanofi and Regenergon. March 15, 2021. Accessed March 15, 2021. https://bit.ly/3tmLCnG

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