Cemiplimab FDA Approval Application for Recurrent or Metastatic Cervical Cancer Withdrawn


Ahead of its Prescription Drug User Fee Act target action date, the supplemental biologics license application for cemiplimab as treatment of metastatic cervical cancer has been withdrawn.

The supplemental biologics license application (sBLA) for the PD-1 inhibitor cemiplimab-wlc (Libatyo) to treat patients with recurrent or metastatic cervical cancer whose disease progressed on or after chemotherapy, has been voluntarily withdrawn by Regeneron Pharmaceutical, Inc and Sanofi, according to a press release by Regeneron.1

The company and the FDA were reportedly unable to agree on key post-marketing studies.

Cemiplimab is a fully human monoclonal antibody that targets the PD-1 immune checkpoint receptor on T-cells. Its mechanism of action involves blocking cancer cells from using the PD-1 pathway to suppress T-cell activation.

The application for cemiplimab in patients with recurrent or metastatic cervical cancer was supported by findings from the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study (NCT03257267) in which cemiplimab demonstrated improvement in overall survival (OS) as well as progression-free survival (PFS) and overall response rate (ORR) compared with chemotherapy.2

“This is a randomized phase 3 trial [conducted] internationally [to evaluate] cemiplimab 350 mg every 3 weeks or investigator’s choice chemotherapy. And it worked. Immunotherapy is better than physician’s choice chemotherapy in the second-line setting. In fact, not only is it better in response rate, it is better in overall survival, with a hazard ratio of 0.69,” said Bradley Monk, MD, FACOG, FACS, gynecologic oncologist, Arizona Oncology, in an interview with Targeted Oncology™.

In the open-label, randomized, multicenter trial, a total of 608 patients with advanced cervical cancer were enrolled and assigned 1:1 to receive either cemiplimab or a chemotherapy option of pemetrexed, vinorelbine, gemcitabine, irinotecan, or topotecan. Cemiplimab was administered at 350 mg via intravenous infusion every 3 weeks, and treatment lasted for up to 96 weeks.

Patients were stratified by histology of squamous cell carcinoma (SCC) versus adenocarcinoma or adenosquamous disease and evaluated for the primary end point of OS. Secondary end points included PFS, ORR, quality of life (QoL), and safety.

Patients enrolled had a median age of 51 years (range, 22-87), and 477 patients had SCC while 131 had adenocarcinoma histology. The ECOG performance status was 0 for 46.5% of the population and 1 for 53.5%.

Cemiplimab achieved a 31% reduction in the risk of death compared with chemotherapy (HR, 0.69; 95% CI, 0.56-0.84; one-sided P = .00011) in the subgroup of patients with SCC. Further, cemiplimab achieved a 25% reduction in the risk of disease progression compared with chemotherapy (HR, 0.75; 95% CI, 0.63-0.89; one-sided P = .00048).

The ORR in the SCC subgroup was 16% with cemiplimab compared with 6% in the chemotherapy arm. The median duration of response (DOR) was 16 months (95% CI, 12 to not evaluable [NE]) with cemiplimab versus 7 months (95% CI, 5-8) with chemotherapy.

In the adenocarcinoma histology subgroup, cemiplimab treatment led to a 27% reduction in the risk of death versus chemotherapy (HR, 0.73; 95% CI, 0.58-0.91; P = .00306). There was also a 29% reduction in the risk of disease progression compared with chemotherapy (HR, 0.71; 95% CI, 0.58-0.86; one-sided P = .00026).

The ORR seen with cemiplimab in patients with adenocarcinoma histology was 18% (95% CI, 13%-23%) compared with 7% (95% CI, 4%-11%) with chemotherapy.

Three hundred of the study subjects were evaluated for safety in the cemiplimab arm and 290 patients were evaluated from the chemotherapy arm. Adverse events (AEs) were reported in 88% of the cemiplimab group compared with 91% of the chemotherapy group. The most common AEs in the cemiplimab arm versus the chemotherapy arm, respectively, were anemia (25% vs 45%), nausea (18% vs 33%), fatigue (17% vs 16%), vomiting (16% vs 23%), decreased appetite (15% vs 16%), and constipation (15% vs 20%)

“Even though pembrolizumab [Keytruda] got approved in June of 2018, that was a single-arm accelerated approval with a very low response rate. And so, there was a need really to test the hypothesis, what the activity of single-agent chemotherapy would be in that second-line setting, and whether single-agent checkpoint inhibitors would truly be more active than physician’s choice of chemotherapy. And that's exactly what EMPOWER-Cervical-1 did,” said Monk, during the interview.

Despite the withdrawal of the sBLA, discussiona between Regeneron and regulatory authorities outside of the United States are ongoing.1


1. Regeneron and sanofi provide regulatory update on Libtayo® (cemiplimab-rwlc) in advanced cervical cancer. News release. Regeneron and Sanofi. January 28, 2022. Accessed Janaury 28, 2022. https://bit.ly/3u7KiZm

2. Tewari KS, Monk BJ, Mathias M, et al. VP4-2021: EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9: Interim analysis of phase III trial of cemiplimab vs. investigator's choice (IC) chemotherapy (chemo) in recurrent/metastatic (R/M) cervical carcinoma. Ann Oncol. 2021; 32(7): 940-941. doi: 10.1016/j.annonc.2021.04.009

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