Phase 3 Cemiplimab Trial in Cervical Cancer Stopped Early With Positive OS Results

Krishnansu S. Tewari, MD

A phase 3 trial for cemiplimab (Libtayo) monotherapy in comparison with chemotherapy in patients with recurrent or metastatic cervical cancer who previously received chemotherapy treatment (NCT03257267) is being stopped early due to a unanimous recommendation by the Independent Data Monitoring Committee due to positive overall survival (OS) results.

Results from the trial will serve as the basis of a regulatory submission for cemiplimab in the treatment of cervical cancer later in the year. Findings from the trial will be presented at an upcoming medical meeting as well.

“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 statement. “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, multi-center study is the largest randomized phase 3 trial in advanced cervical cancer to date, including 608 eligible patients. Patients were randomized to either cemiplimab 350 mg every 3 weeks or investigator’s choice of chemotherapy between pemetrexed, topotecan or irinotecan, gemcitabine, or vinorelbine. Treatment was planned for up to 96 weeks or until treatment discontinuation.

Patients with squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma histologies were all eligible for enrollment, and patients were included in the study regardless of PD-L1 expression level. Eligible patients had recurrent, persistent, and/or metastatic disease with no curative treatment option, tumor progression or recurrence after platinum treatment, an ECOG performance status of 0 or 1, and adequate organ or bone marrow function. Those who were eligible must have received prior bevacizumab (Avastin) and paclitaxel.

Those with significant autoimmune disease, prior treatment with anti–PD-1/PD-L1 therapy or immune-modulating agents, active or untreated brain metastases, immunosuppressive corticosteroid use, active infection, history of pneumonitis, history of hypersensitivity, or a concurrent malignancy were excluded form the study.

The primary end point of the study was OS in patients with recurrent or metastatic cervical cancer with squamous cell carcinoma histology, and secondary end points were progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), safety, and quality of life in patients with squamous cell carcinoma as well as in all eligible histologies.

In line with the protocol of the study, study closeout was considered after 340 OS events had been reported in patients with squamous cell carcinoma.

The median OS in the overall population was 12.0 months in those treated with cemiplimab versus 8.5 months with chemotherapy (HR, 0.69; 95% CI, 0.56-0.84; P < .001). In patients with squamous cell carcinoma, the median OS was 11.1 months with cemiplimab (n = 239) versus 8.8 months with chemotherapy (n = 238) (HR, 0.73; 95% CI, 0.58-0.91; P = .003). Patients with adenocarcinoma had a median OS of 13.3 months with cemiplimab (n = 65) and those treated with chemotherapy (n = 66) had a median OS of 7.0 months (HR, 0.56; 95% CI, 0.36-0.85; P < .005).

No new safety signals were observed for cemiplimab in the cervical cancer setting. Among all patients treated with at least 1 dose of therapy (n = 590), adverse events (AEs) were reported in 88% of those treated with cemiplimab and 91% of those treated with chemotherapy. Serious AEs were observed in 30% and 27% of the cemiplimab and chemotherapy arms, respectively. Treatment discontinuation due to AEs occurred in 8% of patients treated with cemiplimab and 5% of patients treated with chemotherapy.

The most common AEs were anemia (25% with cemiplimab vs 45% with chemotherapy), nausea (18% vs 33%, respectively), fatigue (17% vs 16%), vomiting (16% vs 23%), and constipation (15% vs 20%). AEs observed more commonly with cemiplimab included fatigue (17% with cemiplimab vs 16% with chemotherapy), urinary tract infections (12% vs 9%, respectively), back pain (11% vs 9%), and arthralgia (10% vs 3%).

“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, Regeneron, in a statement. “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.”

Cemiplimab was recently FDA approved for the treatment of patients with advanced non–small cell lung cancer and high PD-L1 expression in the frontline setting and for patients with advanced basal cell carcinoma previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is not appropriate, both in February 2021.

_Reference

_{Phase 3 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. https://bit.ly/3tpTMM7}