Phase 3 Trial of Cemiplimab Monotherapy in Advanced Cervical Cancer Stopped Early Due to Positive Survival Results


Results from a phase 3 trial investigating the programmed cell death protein 1 inhibitor cemiplimab monotherapy compared to chemotherapy showed an overall survival benefit among patients previously treated with chemotherapy whose cervical cancer is recurrent or metastatic.

Results from a phase 3 trial investigating the programmed cell death protein 1 (PD-1) inhibitor cemiplimab (Libtayo) monotherapy compared to chemotherapy showed an overall survival (OS) benefit among patients previously treated with chemotherapy whose cervical cancer is recurrent or metastatic.

Following a unanimous recommendation by the Independent Data Monitoring Committee (IDMC), the trial will be stopped early, with the data already gathered planned for use as the basis for the regulatory submissions in 2021.

"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 trial investigator Krishnansu S. Tewari, MD, professor and director of the Division of Gynecologic Oncology at the University of California, Irvine, 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 this trial where the average age was 51."

This randomized clinical phase 3 trial included women with a median age of 51 years who have either squamous cell carcinoma (SCC) or adenocarcinoma. The randomization then placed some patients into the cemiplimab monotherapy cohort, whereas the other was given an investigator's choice of commonly used chemotherapy, such as pemetrexed, vinorelbine, topotecan, irinotecan, or gemcitabine. In the cemiplimab group, patients were given 350 mg every 3 weeks during the trial.

When compared to the results of the chemotherapy cohort, patients receiving cemiplimab experienced a 31% reduced risk of death. The median survival in the cemiplimab group was 12.0 months (n=304), whereas the median survival was 8.5 months for patients receiving chemotherapy (n=304); hazard ratio (HR): 0.69; 95% confidence interval (CI): 0.56-0.84 (p<0.001).

During the trial, the investigators tested patients with SCC first, and then proceeded to the total population, which included those with adenocarcinoma. Specifically, the investigators observed that patients with SCC receiving cemiplimab had a 27% reduced risk of death, whereas patients with adenocarcinoma had a 44% reduced risk of death.

Among patients with SCC, the median survival on cemiplimab was 11.1 months (n=239), and on chemotherapy it was 8.8 months (n=238); HR: 0.73; 95% CI: 0.58-0.91 (p=0.003). For patients with adenocarcinoma, the median on cemiplimab was 13.3 months (n=65) compared to 7.0 months on chemotherapy (n=66); HR: 0.56; 95% CI: 0.36-0.85 (p<0.005; not adjusted for multiplicity).

Since the primary endpoint for the trial was OS, the IDMC reviewed OS data following the occurrence of approximately 85% of events in patients with SCC, which was in accordance with what was outlined in a protocol-specified interim analysis.

On observation of the significant effect on OS, the IDMC recommended the trial be stopped, with detailed results of the data planned for presentation at an upcoming medical meeting. Additionally, they noted that cemiplimab use for patients with cervical cancer was still investigational and it had not yet been fully reviewed by all regulatory authorities.

During the phase 3 trial, no new safety signals were observed for cemiplimab. In order to assess this area, the investigators looked specifically at patients who received at least 1 dose of study treatment, which included 300 patients in the cemiplimab 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).

Among these patients, adverse events (AEs) were observed in 88% of cemiplimab patients and 91% of chemotherapy patients. Specifically, the investigators found that serious AEs occurred in 30% of cemiplimab patients and 27% of chemotherapy patients.

The investigators observed that the 5 most common AEs among patients were anemia (25% cemiplimab, 45% chemotherapy), nausea (18% cemiplimab, 33% chemotherapy), fatigue (17% cemiplimab, 16% chemotherapy), vomiting (16% cemiplimab, 23% chemotherapy), and constipation (15% cemiplimab, 20% chemotherapy).

Other AEs that at least 10% of patients in the cemiplimab group experienced were fatigue (17% cemiplimab, 16% chemotherapy), urinary tract infections (12% cemiplimab, 9% chemotherapy), back pain (11% cemiplimab, 9% chemotherapy), and arthralgia (10% cemiplimab, 3% chemotherapy). Additionally, the need to discontinue treatment due to the experience of AEs occurred in 8% of cemiplimab patients and 5% of chemotherapy patients.

"Recurrent or metastatic cervical cancer is notoriously difficult to treat and has no approved standard of care after first-line chemotherapy," said Israel Lowy, MD, PhD, senior vice president, translational and clinical sciences, Oncology, at Regeneron, in the 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."

In 2018, cemiplimab was approved as the first systemic treatment for patients with advanced cutaneous SCC. The FDA’s approval of cemiplimab monotherapy was then specified to be for patients with advanced non-small cell lung cancer whose tumors have high PD-L1 expression.

The FDA also recently authorized the use of cemiplimab as the first immunotherapy for patients with basal cell carcinoma previously treated with a hedgehog pathway inhibitor (HHI) or for whom an HHI is not appropriate, whose cancer is either locally advanced or metastatic. For locally advanced cancer, the FDA gave full approval, and for metastatic cancer accelerated approval.

"We are committed to developing therapies for cancers with high unmet needs including patients with advanced cervical cancer," said Peter C. Adamson, MD, Global Development Head, Oncology and Pediatric Innovation at Sanofi, in the press release. "Combined with data from our non-melanoma skin cancer and lung cancer studies, these data contribute to the growing evidence demonstrating the significant potential of Libtayo to treat a spectrum of difficult-to-treat cancers."


Phase 3 Trial of Libtayo (cemiplimab) Monotherapy in Advanced Cervical Cancer Stopped Early for Positive Result on Overall Survival. Tarrytown, NY: Regeneron Pharmaceuticals; March 15, 2021. Accessed March 19, 2021.

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