FDA Grants Priority Review to Cemiplimab-rwlc as First-Line Treatment for Advanced NSCLC

The FDA has granted priority review to the supplemental biologics license application (sBLA) for the PD-1 inhibitor cemiplimab-rwlc (Libtayo) as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with 50% or more PD-L1 expression, according to Regeneron, the developer of the agent.¹

A target action date has been set by the FDA for February 28, 2021.

Acceptance of the sBLA is supported by results from an open-label, randomized, multicenter, phase 3 trial that investigated the first-line treatment of cemiplimab-rwlc monotherapy compared to platinum-doublet chemotherapy in patients with locally advanced or metastatic NSCLC whose tumor cells expressed PD-L1, including those whose cancers had confirmed PD-L1 expression of 50% or more using the PD-L1 IHC 22C3 pharmDx kit. Results from the trial were presented at the 2020 European Society for Medical Oncology (ESMO) Virtual Congress in September.

"In new analyses presented at ESMO, [cemiplimab-rwlc] 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," trial investigator Ahmet Sezer, MD, associate professor in the Department of Medical Oncology at Başkent University in Adana, Turkey, said in a press release.² "These results support [cemiplimab-rwlc] as a potential new option for anti-PD-1 monotherapy in first-line advanced non-small cell lung cancer."

Patients included in the trial were randomized 1:1 to receive either 350 mg of cemiplimab-rwlc administered intravenously every 3 weeks for up to 108 weeks or an investigator-selected, standard-of-care, platinum-based, doublet chemotherapy regimen for 4 to 6 cycles (with or without histology relevant maintenance pemetrexed chemotherapy).

The co-primary end points were overall survival (OS) and progression-free survival (PFS), and secondary end points included overall response rate (ORR), duration of response, and quality of life.

Notably, the late-breaking ESMO presentation expanded on topline results shared in April. In the overall trial population (n = 710), the median follow-up was 13 months for both cemiplimab-rwlc (n = 356; range: <1-32 months) and chemotherapy (n = 354; range: <1-32 months).

Among these patients, cemiplimab-rwlc reduced the risk of death by 32% (HR, 0.68; 95% CI, 0.53-0.87; P = .0022). The median OS was 22 months among patients treated with cemiplimab-rwlc (95% CI, 18 months to not yet evaluable) compared to 14 months in the chemotherapy population (95% CI, 12-19 months).

In addition, 41% of patients in the cemiplimab-rwlc arm saw reduced risk of disease progression (HR, 0.59; 95% CI, 0.49-0.72; P < .0001). The median PFS was 6.2 months (95% CI, 4.5-8.3 months) compared to 5.6 months (95% CI, 4.5-6.1 months).

Moreover, the ORR was 37% for those treated with cemiplimab-rwlc (95% CI, 32-42%), including 3% with a complete response (CR) and 33% with a partial response (PR), compared to a 21% ORR in the chemotherapy arm (95% CI, 17-25%), including a 1% CR and a 20% PR rate. The median duration of exposure to cemiplimab-rwlc was 27 weeks (range: <1-115 weeks) and 18 weeks for chemotherapy (range: <1-87 weeks).

Notably, a prespecified analysis of data from patients whose cancers had confirmed PD-L1 expression of at least 50% (n = 563) was also conducted by investigators. In this group, the median follow-up was 11 months for both cemiplimab-rwlc (n = 283; range: <1-32 months) and chemotherapy (n = 280; range: <1-30 months). Within this cohort, cemiplimab-rwlc demonstrated a 43% reduced risk of death (HR, 0.57; 95% CI, 0.42-0.77; P = .0002) and a 46% reduced risk of disease progression (HR, 0.54; 95% CI, 0.43-0.68; P < .0001).

The median OS was not reached in this population of patients treated with cemiplimab-rwlc (95% CI, 18 months to not yet evaluable) compared to 14 months for those in the chemotherapy arm (95% CI, 11-18). The median PFS was 8 months (95% CI, 6-9) compared to 6 months (95% CI, 5-6). Additionally, those in the cemiplimab-rwlc arm saw a 39% ORR (95% CI, 34-45%), including a 2% CR and 37% PR rate, compared to a 20% ORR in the chemotherapy arm (95% CI, 16-26%), with a 1% CR and 19% PR rate.

Importantly, the trial also identified a direct correlation between tumor response and PD-L1 expression level in patients treated with cemiplimab-rwlc. The ORR was highest (46%; range, 36-56) in tumors with at least 90% PD-L1 expression, with target tumors shrinking by more than 40% after 6 months of treatment on average (per last observation carried forward method). This correlation with PD-L1 expression level was not observed with chemotherapy, however.

Regarding safety, adverse events (AEs) were observed in 88% of patients treated with cemiplimab-rwlc and 94% of those treated with chemotherapy. Grade 3 or higher AEs occurred in 37% of those in the cemiplimab-rwlc arm and 49% of those in the chemotherapy arm.

Further, immune-mediated AEs were reported in 17% of those treated with cemiplimab-rwlc and included hypothyroidism (6%), hyperthyroidism (4%), pneumonitis (2%), hepatitis (2%), skin adverse reaction (2%), arthritis, increased blood thyroid stimulating hormone, thyroiditis, colitis, nephritis, and peripheral neuropathy (each 1%). Treatment discontinuation due to an AE occurred in 6% of patients in the cemiplimab-rwlc arm and 4% of patients in the chemotherapy arm. No new safety signals were observed with cemiplimab-rwlc.

Cemiplimab-rwlc is the first systemic treatment approved in the US and EU for adults with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. However, the use of cemiplimab-rwlc to treat advanced NSCLC is investigational and has not been fully evaluated by any regulatory authority.

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]. Tarrytown, New York. Published October 29, 2020. Accessed October 29, 2020. https://investor.regeneron.com/news-releases/news-release-details/fda-accepts-priority-review-libtayor-cemiplimab-rwlc-advanced

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]. Tarrytown, NY and Paris. Published September 21, 2020. Accessed October 29, 2020. https://investor.regeneron.com/news-releases/news-release-details/late-breaking-esmo-presentation-shows-libtayor-cemiplimab