The primary endpoint of overall survival ( OS ) was met in a phase 3 trial comparing the PD-1 inhibitor Cemiplimab ( Libtayo ) to Platinum doublet chemotherapy in patients with first-line locally advanced or metastatic non-small cell lung cancer ( NSCLC ) that tested positive for PD-L1 in greater than or equal to 50% of tumor cells, were presented.
Based on a recommendation by the independent Data Monitoring Committee to stop the trial early, the trial will be modified to allow all patients to receive Cemiplimab for this investigational use.

A protocol-specified interim analysis conducted by the Independent Data Monitoring Committee has demonstrated that patients treated with Cemiplimab monotherapy had a significant increase in overall survival. Cemiplimab has decreased the risk of death by 32.4% ( hazard ratio, HR=0.676; CI: 0.525-0.870, p=0.002 ), compared to Platinum doublet chemotherapy, despite a third of patients entering the trial within the past six months and all chemotherapy patients being able to crossover to Cemiplimab if their disease progressed.
No new Cemiplimab safety signal was identified.

The open-label, randomized, multi-center phase 3 trial included 712 patients ( of whom 710 were included in the interim analysis ) with locally advanced NSCLC ( stage IIIB/C ), who were not candidates for surgical resection or definitive chemoradiation or had progressed after treatment with definitive chemoradiation, or previously untreated metastatic NSCLC ( stage IV ).
Patients were randomized 1:1 to receive either Cemiplimab 350 mg administered intravenously every three weeks for up to 108 weeks, or an investigator-selected, standard-of-care, Platinum-based, doublet chemotherapy regimen for four to six cycles ( with or without maintenance Pemetrexed chemotherapy ).
The co-primary endpoints were overall survival and progression free surviva, and secondary endpoints included overall response rate, duration of response and quality of life.
The trial was designed to reflect current and emerging treatment paradigms. Inclusion criteria allowed patients with NSCLC that had: controlled hepatitis B, hepatitis C or HIV; pre-treated and stable brain metastases; and/or locally advanced disease that had progressed on definitive chemoradiation.
Patients whose disease progressed in the trial were able to change their therapy: those in the chemotherapy arm were allowed to crossover into the Cemiplimab arm, while those in the Cemiplimab arm were allowed to combine Cemiplimab treatment with four to six cycles of 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.

Lung cancer is the leading cause of cancer death worldwide. In 2020, more than 2.2 million new cases are expected to be diagnosed globally, with 228,800 new cases in the U.S. alone. Approximately 85% of all lung cancers are NSCLC, with an estimated 25% to 30% of cases expected to test positive for PD-L1 in 50% or more of tumor cells. While immunotherapies have transformed advanced NSCLC treatment in recent years, there remains an unmet need to optimize the identification and treatment of patients with high PD-L1 expression. ( Xagena )

Source: Sanofi, 2020

Xagena_Medicina_2020