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Libtayo as monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of 50% or more, FDA has approved

The FDA ( U.S. Food and Drug Administration ) has approved the PD-1 inhibitor Libtayo ( Cemiplimab-rwlc; Cemiplimab ) for the first-line treatment of patients with advanced non-small cell lung cancer ( NSCLC ) whose tumors have high PD-L1 expression ( tumor proportion score [ TPS ] 50% or more ), as determined by an FDA-approved test.
Patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation, and the tumors must not have EGFR, ALK or ROS1 aberrations.

The data supporting the Libtayo approval are based on an analysis of 710 patients who were randomized to receive treatment in a phase 3 trial; eligible patients were intended to have PD-L1 expression of 50% or more.
In this patient population, Libtayo has reduced the risk of death by 32% compared to chemotherapy.

Median overall survival was 22.1 months ( 95% CI:17.7, NE ) for patients in the Cemiplimab-rwlc arm compared with 14.3 months ( 95% CI: 11.7, 19.2 ) in the chemotherapy arm ( hazard ratio, HR 0.68; 95% CI: 0.53, 0.87, p=0.0022 ).
Median progression-free survival per BICR was 6.2 months ( 4.5, 8.3 ) in the Cemiplimab-rwlc arm and 5.6 months ( 4.5, 6.1 ) in the chemotherapy arm ( HR 0.59; 95% CI: 0.49, 0.72, p less than 0.0001 ).
Confirmed overall response rate ( ORR ) per BICR was 37% ( 95% CI: 32, 42 ) and 21% ( 95% CI: 17, 25 ) in the Cemiplimab-rwlc and chemotherapy arms, respectively.

Due to PD-L1 testing issues, an additional prespecified analysis was performed in 563 patients with proven PD-L1 expression of 50% or more, according to the FDA-approved assay.
This analysis has shown that Libtayo has reduced the risk of death by 43% compared to chemotherapy.

Safety was assessed in 355 patients in the Libtayo group ( median duration of exposure: 27 weeks; range: 9 days to 115 weeks ) and 342 patients in the chemotherapy group ( median duration of exposure: 18 weeks; range: 18 days to 87 weeks ).
Adverse reactions that occurred more commonly in the Libtayo group and in at least 10% of patients were rash ( 15% Libtayo, 6% chemotherapy ) and cough ( 11% Libtayo, 8% chemotherapy ).
The most frequent serious adverse reactions in at least 2% of patients were pneumonia ( 5% Libtayo, 6% chemotherapy ) and pneumonitis ( 2% Libtayo, 0% chemotherapy ).

Treatment was permanently discontinued due to adverse reactions in 6% of Libtayo patients; adverse reactions resulting in permanent discontinuation in at least 2 patients were pneumonitis, pneumonia, ischemic stroke and increased aspartate aminotransferase.

No new Libtayo safety signals were observed.

The open-label, randomized, multi-center phase 3 trial, called EMPOWER-Lung 1, was designed to investigate the first-line treatment of Libtayo monotherapy compared to Platinum-doublet chemotherapy in patients with advanced NSCLC who tested positive for PD-L1 in greater than or equal to 50% of tumor cells and without EGFR, ALK or ROS1 aberrations.
PD-L1 expression was confirmed using the Agilent Dako PD-L1 IHC 22C3 pharmDx kit.
The primary endpoints were overall survival and progression-free-survival, and secondary endpoints included overall response rate, duration of response and quality of life.
The trial randomized 710 patients with either previously untreated metastatic NSCLC ( stage IV ) or locally advanced NSCLC ( stage IIIB/C ) who were not candidates for surgical resection or definitive chemoradiation or who had progressed after treatment with definitive chemoradiation.
Enrolled patients included those with disease characteristics frequently underrepresented in pivotal advanced NSCLC trials. Among them, 12% had pre-treated and clinically stable brain metastases and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation.
Patients whose disease progressed in the trial were able to change their therapy: those assigned to chemotherapy were allowed to crossover to Libtayo treatment following disease progression, while those assigned to Libtayo monotherapy were allowed to combine Libtayo treatment with 4 to 6 cycles of chemotherapy following disease progression. There was a more than 70% crossover rate to Libtayo following disease progression on chemotherapy.

Cemiplimab is a fully-human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By binding to PD-1, Cemiplimab has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.

Across all of its approved indications, the recommended dose of Libtayo is 350 mg administered as an intravenous infusion over 30 minutes every three weeks, until disease progression or unacceptable toxicity.
Libtayo is available as a single-dose 350 mg vial.

Lung cancer is the leading cause of cancer death worldwide. In 2020, an estimated 2.2 million and 225,000 new cases were diagnosed worldwide and in the U.S, respectively.
Approximately 84% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages and an estimated 25% to 30% of cases expected to test positive for PD-L1 in greater than or equal to 50% of tumor cells. ( Xagena )

Source: Regeneron & Sanofi, 2021