FDA Grants Priority Review to Cemiplimab for Advanced Cervical Cancer

The FDA has granted priority review to a supplemental biologics license application (sBLA) for the use of cemiplimab-rwlc (Libtayo) in the treatment of patients with recurrent or metastatic cervical cancer whose disease progressed on, or after, chemotherapy.¹

The application is supported by data from a phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 (NCT03257267), in which cemiplimab resulted in a statistically significant and clinically meaningful improvement in survival when given to patients with recurrent or metastatic cervical carcinoma following progression on frontline platinum-containing chemotherapy.²

At a median follow-up of 16.8 months (range, 6.0-38.2), the median overall survival (OS) with cemiplimab was 11.1 months (95% CI, 9.2-13.4) vs 8.8 months (95% CI, 7.6-9.8) with chemotherapy in the squamous cell carcinoma population (SCC; HR, 0.73; 95% CI, 0.58-0.91; one-sided P = .00306). 

In the population of patients with adenocarcinoma or adenosquamous carcinoma (AC), at a median follow-up of 21.9 months (95% CI, 6.9-36.6), the median OS with the immunotherapy was 13.3 months (95% CI, 9.6-17.6) vs 7.0 months (95% CI, 5.1-9.7) with chemotherapy (HR, 0.56; 95% CI, 0.36-0.85; one-sided P < .005). 

In the total population, at a median follow-up of 18.2 months (range, 6.0-38.2), the median OS with cemiplimab and chemotherapy was 12.0 months (95% CI, 10.3-13.5) and 8.5 months (95% CI, 7.5-9.6), respectively (HR, 0.69; 95% CI, 0.56-0.84; one-sided P = .00011).

The regulatory agency is anticipated to decide on the sBLA by January 30, 2022, under the Prescription Drug User Fee Act.

The open-label, multicenter phase 3 trial enrolled patients with recurrent and metastatic cervical cancer who had progressed on platinum-based chemotherapy. Participants were enrolled irrespective of PD-L1 tumor expression status or histology. Patients needed to have an ECOG performance status of 0 or 1.

A total of 608 patients were enrolled to the trial; 477 had SCC and 131 had AC. Study participants were randomized 1:1 to receive either cemiplimab at 350 mg every 3 weeks or investigator’s choice of chemotherapy, which could include any of the following options: pemetrexed at 500 mg/m² every 3 weeks; gemcitabine at 1000 mg/m² on days 1 and 8 and every 21 days; topotecan at a daily dose of 1 mg/m² for 5 days, every 21 days; irinotecan at a weekly dose of 100 mg/m² for 4 weeks, followed by 10 to 14 days of rest; or vinorelbine at 30 30 mg/m² on days 1 and 8 and every 21 days.

Patients were treated for up to 96 weeks with an option for retreatment. Stratification factors included histology (SCC vs AC), geographic region, prior bevacizumab (Avastin; yes vs no), and ECOG performance status (0 vs 1).

The primary end point of the research was OS, and key secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response, safety, and quality of life. Exploratory end points comprised pharmacokinetics, immunogenicity, biomarkers, and pharmacodynamics.

Two interim analyses were prespecified according to the study protocol. At the first interim analysis it was recommended by the independent data monitoring committee (IDMC) that the trial continue. At the time of the second interim analysis, the IDMC recommended that the trial be stopped early for efficacy.

The median age of study participants across the treatment arms was 51.0 years, and 87.7% of patients were under the age of 65 years. Most patients, or 61.8%, were enrolled to clinical sites that were not North America or Asia, and 53.5% had an ECOG performance status of 1. Additionally, 77.8% had a SCC histology, 19.1% had adenocarcinoma, and 3.1% had adenosquamous carcinoma.

The majority of patients (94.4%) had metastatic disease, 56.9% previously received 1 line of therapy for recurrent or metastatic disease, and 51.3% did not receive prior bevacizumab.

Additional data from the trial showed that among those without PD-L1 expression, the median OS with cemiplimab was 12.7 months (95% CI, 9.6-14.5) vs 8.7 months (95% CI, 7.4-9.7) with chemotherapy (HR, 0.64; 95% CI, 0.49-0.84). In those with PD-L1 expression, the median OS was 11.1 months (95% CI, 8.0-15.0) vs 8.2 months (95% CI, 6.7-10.8), respectively (HR, 0.78; 95% CI, 0.57-1.07).

In those with PD-L1 expression of 1% or higher on tumor cells (TC), the median OS with cemiplimab was 13.9 months (95% CI, 9.6–not evaluable) vs 9.3 months (95% CI, 7.0-11.4) with chemotherapy (HR, 0.70; 95% CI, 0.46-1.05). In the subset of patients with a TC of less than 1%, the median OS in the investigative and control arms was 7.7 months (95% CI, 4.3-12.3) and 6.7 months (95% CI, 3.9-9.5), respectively (HR, 0.98; 95% CI, 0.59-1.62).

The median PFS in all patients who received cemiplimab was 2.8 months (95% CI, 2.6-3.9) vs 2.9 months (95% CI, 2.7-3.4) with chemotherapy (HR, 0.75; 95% CI, 0.63-0.89). In the subset of patients without PD-L1 expression, the median PFS in the investigative and control arms was 2.8 months (95% CI, 2.7-4.0) and 2.8 months (95% CI, 2.6-3.5), respectively (HR, 0.71; 95% CI, 0.56-0.90). In those with PD-L1 expression, the median PFS was 2.8 months (95% CI, 1.7-4.0) vs 2.9 months (95% CI, 2.6-4.0), respectively (HR, 0.82; 95% CI, 0.62-1.08).

In the total population, the odds ratio (OR) for ORR between cemiplimab and chemotherapy was 2.98 (95% CI, 1.71-5.22). Notably, objective responses were reported in patients with a PD-L1 expression of 1% or higher (18.3%; 95% CI, 10.6%-28.4%; n = 15/82) and those with an expression of less than 1% (11.4%; 95% CI, 3.8%-24.6%; n = 5/44). In the subset of patients without PD-L1 expression, the OR was 3.73 (95% CI, 1.71-8.13); the OR in those with PD-L1 expression was 2.28 (95% CI, 1.02-5.12).

The overall mean change from baseline Global Health Status/quality of life favored cemiplimab in the overall population (one-sided nominal P < .001). No new safety signals were reported.

References

1. FDA accepts Libtayo (cemiplimab-rwlc) for priority review for advanced cervical cancer. News release. Regeneron Pharmaceuticals, Inc. September 28, 2021. Accessed September 28, 2021. https://bit.ly/3m5psnU
2. Tewari KS, Monk BJ, Vergote I, 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):P940-P941. doi:10.1016/j.annonc.2021.04.009