Phase III trial of Libtayo as monotherapy for first-line advanced NSCLC stopped early due to highly significant improvement in overall survival.- Sanofi + Regeneron

Sanofi and Regeneron Pharmaceuticals, Inc. announced the primary endpoint of overall survival (OS) was met in a Phase III trial comparing the PD-1 inhibitor Libtayo (cemiplimab) 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 50% of tumor cells. 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 Libtayo for this investigational use. The data will form the basis of regulatory submissions in the U.S. and European Union (EU) in 2020.

A protocol-specified interim analysis conducted by the Independent Data Monitoring Committee demonstrated that patients treated with Libtayo monotherapy had a significant increase in OS. Libtayo decreased the risk of death by 32.4% (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 Libtayo if their disease progressed. No new Libtayo safety signal was identified. Detailed trial data will be presented at a future medical meeting.

About the Phase III Trial : The open-label, randomized, multi-center Phase III trial investigated the first-line treatment of Libtayo monotherapy compared to platinum doublet chemotherapy in squamous or non-squamous advanced NSCLC that tested positive for PD-L1 in greater than 50% of tumor cells. The 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). The trial offers the largest data set from a pivotal trial currently available for this patient population.

Patients were randomized 1:1 to receive either Libtayo 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 are OS and progression free survival (PFS), and secondary endpoints include 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 Libtayo arm, while those in the Libtayo arm were allowed to combine Libtayo treatment with four to six cycles of chemotherapy.

A separate Phase III trial evaluating a first-line combination of Libtayo and chemotherapy in patients with advanced NSCLC irrespective of PD-L1 expression is also underway and expected to be fully enrolled in 2020.