FDA Grants Priority Review to Cemiplimab for Advanced NSCLC With High PD-L1 Expression

The FDA has granted a priority review designation to a supplemental biologics license application (sBLA) for cemiplimab-rwlc (Libtayo) for the frontline treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with a PD-L1 expression of 50% or greater.¹

The application is based on data from a phase 3 trial that compared the use of single-agent cemiplimab with platinum-doublet chemotherapy in patients with locally advanced or metastatic disease whose tumors expressed PD-L1, including those with expression of 50% or greater. Results presented during the 2020 ESMO Virtual Congress showed that cemiplimab resulted in a 43% reduction in the risk of death in the subset of patients with high PD-L1 expression (HR, 0.57; 95% CI, 0.42-0.77; P =.0002).2 In the overall trial population, the PD-1 inhibitor reduced the risk of death by 32% (HR, 0.68; 95% CI, 0.53-0.87; P =.0022).

Under the Prescription Drug User Fee Act, the FDA must make a decision on the sBLA by February 28, 2021.

“In…analyses presented at ESMO, [cemiplimab] reduced the risk of death by 43% in patients whose cancer had confirmed PD-L1 expression of 50% or greater. This is notable given that nearly three-quarters of patients crossed over from chemotherapy following disease progression and 12% of patients had pretreated and stable brain metastases,” Ahmet Sezer, MD, associate professor in the Department of Medical Oncology at Baskent University and trial investigator, stated in a press release.² “These results support [cemiplimab] as a potential new option for anti–PD-L1 monotherapy in first-line advanced NSCLC.”

A total of 710 patients were evaluated on the trial and additional results showed that the median overall survival (OS) with cemiplimab was 22 months (95% CI, 18–not evaluable [NE]) versus 14 months with chemotherapy (95% CI, 12-19).

Moreover, the PD-1 inhibitor reduced the risk of disease progression by 41% (HR, 0.59; 95% CI, 0.49-0.72; P <.0001). The median progression-free survival (PFS) with cemiplimab was 6.2 months (95% CI, 4.5-8.3) versus 5.6 months (95% CI, 4.5-6.1) with chemotherapy.

Cemiplimab elicited an objective response rate (ORR) of 37% (95% CI, 32%-42%); this included a complete response (CR) rate of 3% and a partial response (PR) rate of 33%. In comparison, chemotherapy resulted in a 21% ORR (95% CI, 17%-25%) with a 1% CR rate and a 20% PR rate.

Results from a prespecified analysis of 563 patients who had PD-L1 expression of 50% or greater showed that cemiplimab led to a 43% reduction in the risk of death (HR, 0.57; 95% CI, 0.42-0.77; P =.0002). In this subset, the median OS had not yet been reached (95% CI, 18–NE) with cemiplimab versus 14 months (95% CI, 11-18) with chemotherapy.

In these patients, the PD-1 inhibitor reduced the risk of progressive disease by 46% (HR, 0.54; 95% CI, 0.43-0.68; P <.0001). The median PFS with cemiplimab and chemotherapy was 8 months (95% CI, 6-9) versus 6 months (95% CI, 5-6). Cemiplimab induced an ORR of 39% (95% CI, 34%-45%) in this patient subgroup, with a CR rate of 2% and a PR rate of 37%. In contrast, the ORR in the chemotherapy arm was 20% (95% CI, 16%-26%), with a 1% CR rate and a 19% PR rate.

Investigators also demonstrated a direct correlation between tumor response and PD-L1 expression level in patients who received cemiplimab. Patients who had a PD-L1 expression of 90% or greater had the highest ORR with the PD-1 inhibitor, at 46% (range, 36%-56%); target tumors were found to shrink by more than 40% following an average of 6 months of cemiplimab. Notably, this correlation was not reported with chemotherapy.

The median duration of exposure to cemiplimab in the overall patient population was 27 weeks versus 18 weeks with chemotherapy. With regard to safety, 88% of patients who received cemiplimab experienced adverse effects (AEs) versus 95% of those given chemotherapy.

Moreover, 37% versus 49% of patients who received cemiplimab and chemotherapy, respectively, experienced immune-mediated AEs. These toxicities included hypothyroidism (6%), hyperthyroidism (4%), pneumonitis (2%), hepatitis (2%), skin adverse reaction (2%), arthritis (1%), increased blood thyroid-stimulating hormone (1%), thyroiditis (1%), colitis (1%), nephritis (1%), and peripheral neuropathy (1%).

Six percent of patients on the investigational arm had to discontinue treatment with cemiplimab because of an AE compared with 4% of those on the control arm.

Cemiplimab is also being evaluated by the European Medicines Agency for use in patients with advanced NSCLC who have a PD-L1 expression of 50% or greater; a regulatory decision is anticipated in the second quarter of 2021.

In September 2018, cemiplimab was approved by the FDA for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or patients with locally advanced CSCC who are not candidates for curative surgery or curative radiation based on a combined analysis of data from the phase 2 EMPOWER-CSCC-1 trial and 2 advanced CSCC expansion cohorts from Study 1423.

References

1. FDA accepts for priority review Libtayo (cemiplimab-rwlc) for advanced non-small cell lung cancer with PD-L1 expression of ≥50%. News release. Regeneron Pharmaceuticals, Inc. October 29, 2020. Accessed October 29, 2020. https://bit.ly/34E7p0m.
2. Late-breaking ESMO presentation shows Libtayo (cemiplimab) monotherapy increases overall survival in first-line advanced non-small cell lung cancer with PD-L1 expression of ≥50%. News release. Regeneron Pharmaceuticals, Inc. September 21, 2020. Accessed October 29, 2020. https://bit.ly/3ea6d8i.