FDA Grants Priority Review to Cemiplimab for Recurrent/Metastatic Cervical Cancer

The FDA has accepted and granted priority review to the supplemental biologics license application (sBLA) for the PD-1 inhibitor cemiplimab-wlc (Libatyo) for the treatment of patients with recurrent or metastatic cervical cancer whose disease progressed on or after chemotherapy, according to a press release issued by Regeneron.¹

Findings from the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study (NCT03257267) supported the sBLA for cemiplimab. From the study results, cemiplimab became the first immunotherapy to show improved overall survival (OS) as well as progression-free survival (PFS) and overall response rate (ORR) compared with chemotherapy.²

In the open-label, randomized, multicenter phase 2 study, 608 patients with advanced cervical cancer were 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.^2,3

Stratified by histology of squamous cell carcinoma (SCC) versus adenocarcinoma or adenosquamous (AC) disease, the primary end point investigated was OS. Secondary end points included PFS, ORR, quality of life (QoL), and safety.

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

Patients were exposed to cemiplimab treatment for a median of 15 weeks (range, 1.4-100.7). 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, the experimental arm had 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).

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

Patients with AC histology also favored cemiplimab over chemotherapy. Cemiplimab achieved a 27% reduction in the risk of death in this subgroup 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 observed with cemiplimab in patients with AC histology was 18% (95% CI, 13%-23%) compared with 7% (95% CI, 4%-11%) with chemotherapy.

Another key finding in EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 was that treatment with cemiplimab improved QoL outcomes in patients compared with chemotherapy.

Safety was assessed in 300 patients from the cemiplimab arm and 290 patients from the chemotherapy arm, and adverse events (AEs) occurred in 88% versus 91%, respectively.

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 %), decreased appetite (15% vs 16%), and constipation (15% vs 20%)

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 agent has shown promise in multiple solid tumors and hematologic malignancies.¹

Cemplimab’s sBLA for the treatment of patients with recurrent or metastatic cervical cancer whose disease progressed on or after chemotherapy will be review as a part of the FDA’s Project Orbis, allowing concurrent review by regulatory bodies in Australia, Brazil, Canada, and Switzerland, as well as other countries. The target action date for a decision on the potential approval has been set to January 30, 2022.

_Reference:

_{1. FDA accepts Libtayo® (cemiplimab-rwlc) for priority review for advanced cervical cancer. News release. Regeneron. September 28. 2021. Accessed September 28, 2021. https://bit.ly/39GMyLK}

_{2. Positive phase 3 Libtayo® (cemiplimab) results in advanced cervical cancer presented at ESMO virtual plenary. News release. September 28, 2021. Accessed September 28, 2021. https://bit.ly/3ofLVkI}

_{3. 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. Presented at: 2021 ESMO Congress; September 16-21, 2021; virtual. Abstract VP4-2021}