Cemiplimab Phase 3 Trial Stopped Early Due to OS Benefit in Advanced Cervical Cancer

Krishnansu S. Tewari, MD

A phase 3 trial evaluating single-agent cemiplimab (Libtayo) will be stopped early due to positive results demonstrating an overall survival (OS) benefit over chemotherapy in patients with recurrent or metastatic cervical cancer who previously received chemotherapy.¹

The PD-1 inhibitor was found to reduce the risk of death by 31% in the total patient population. The median OS with cemiplimab monotherapy was 12.0 months in the 304 patients included in the experimental arm vs 8.5 months with chemotherapy in the 304 patients enrolled to the control arm (HR, 0.69; 95% CI, 0.56-0.84; P <.001).

When looking at disease subtypes, cemiplimab was found to reduce the risk of death by 27% in patients with squamous cell carcinoma and by 44% in those with adenocarcinoma. The median OS was 11.1 months with single-agent cemiplimab (n = 239) vs 8.8 months with chemotherapy (n = 238) in patients with squamous cell carcinoma (HR, 0.73; 95% CI, 0.58-0.91; P = .003). In patients with adenocarcinoma, the median OS with cemiplimab monotherapy (n = 65) was 13.3 months vs 7.0 months with chemotherapy (n = 66; HR, 0.56; 95% CI, 0.36-0.85; P <.005).

Based on the data, the Independent Data Monitoring Committee (IDMC) for the trial unanimously decided to stop the trial early. The findings will serve as the basis for regulatory submissions this year, according to Sanofi, co-developer of the drug.

“[Cemiplimab] monotherapy is the first medicine to demonstrate an improvement in OS in women with recurrent or metastatic cervical cancer following progression on platinum-based chemotherapy in a phase 3 trial,” Krishnansu S. Tewari, MD, trial investigator, as well as professor and director of the Division of Gynecologic Oncology at the University of California, Irvine, stated 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.”

The open-label, multicenter phase 3 trial enrolled patients with advanced cervical cancer who had either squamous cell carcinoma or adenocarcinoma and who had progressed on chemotherapy. Patients enrolled from 14 countries: the United States, Japan, Taiwan, South Korea, Canada, Russia, Poland, Spain, Brazil, Australia, the United Kingdom, Italy, Greece, and Belgium. The median age of participants was 51 years.

Study participants were randomized to receive either single-agent cemiplimab at a dose of 350 mg every 3 weeks or investigator’s choice of chemotherapy in the form of either pemetrexed, vinorelbine, topotecan, irinotecan, or gemcitabine.

The primary end point of the trial was OS, which was evaluated among patients with squamous cell carcinoma and then in the total study population. The IDMC assessed the OS data when approximately 85% of events had occurred among patients with squamous cell carcinoma, per a protocol-specified interim analysis. Because of the positive OS data, the committee recommended that the trial be stopped.

Detailed data will be revealed at an upcoming medical conference, according to Sanofi.

Participants who were given at least 1 dose of the study treatment were analyzed for safety; this included 300 patients in the cemiplimab arm and 290 patients in the chemotherapy arm. Those in the experimental arm had a median exposure of 15 weeks vs 10 weeks in the control arm. Eighty-eight percent of patients who received cemiplimab experienced toxicities compared with 91% of those given chemotherapy. Serious adverse effects (AEs) were experienced by 30% and 27% of patients in the experimental and control arms, respectively.

The most frequently reported AEs comprised anemia (25%, cemiplimab; 45%, chemotherapy), nausea (18% vs 33%, respectively), fatigue (17% vs 16%), vomiting (16% vs 23%), and constipation (15% vs 20%). Other toxicities included fatigue (17% vs 16%), urinary tract infections (12% vs 9%), back pain (11% vs 9%), and arthralgia (10% vs 3%).

Eight percent of patients who received cemiplimab discontinued treatment vs 5% of those who were given chemotherapy.

“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, added in the release. “This trial, which enrolled patients regardless of their PD-L1 status, demonstrated that [cemiplimab] helped patients with recurrent or metastatic cervical cancer live longer after progression on prior chemotherapy. This is the fourth patient population in which [cemiplimab] has shown clinical benefit and we look forward to submitting the results to regulatory authorities later this year.”

Most recently, in February 2021, the FDA approved cemiplimab monotherapy for use in the frontline treatment of patients with advanced non–small cell lung cancer with a PD-L1 expression level of 50% or higher. Earlier that month, the agent was given the green light by the FDA for use in patients with advanced basal cell carcinoma who had previously received a hedgehog pathway inhibitor (HHI) or for whom a HHI is not appropriate. In September 2018, the FDA approved the PD-1 inhibitor for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or those with locally advanced CSCC who are not eligible for curative surgery or curative radiation.

Reference

1. Phase 33 trial of Libtayo (cemiplimab) monotherapy in advanced cervical cancer stopped early for positive result on overall survival. News release. Sanofi. March 15, 2021. Accessed March 15, 2021. http://bit.ly/3rRRIfj