Regeneron and Sanofi announced the primary endpoint of overall survival (OS) was met in a Phase 3 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 ≥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.

"While demonstrating a survival benefit in first-line NSCLC has been challenging for immunotherapies, the one FDA-approved anti-PD-1 monotherapy has changed the therapeutic paradigm," said George D. Yancopoulos, M.D., Ph.D., Co-Founder, President and Chief Scientific Officer of Regeneron. "We are pleased with the results of this trial that demonstrate the survival benefit of Libtayo in these patients and hope it may become a potential alternative for physicians and patients."

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.

"This is the largest clinical trial evaluating a PD-1 inhibitor as a first-line monotherapy in patients with advanced non-small cell lung cancer with high PD-L1 expression. These positive results are extremely encouraging, and we look forward to advancing a potential new treatment option for these patients," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "We are grateful to all of the investigators and patients who participated in the global trial."

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% 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.

Libtayo is being jointly developed and commercialized by Regeneron and Sanofi under a global collaboration agreement. Libtayo was invented using Regeneron's proprietary VelocImmune? technology that utilizes a proprietary genetically-engineered mouse platform endowed with a genetically-humanized immune system to produce optimized fully-human antibodies. VelocImmune technology has been used to create multiple antibodies including Dupixent? (dupilumab), Praluent? (alirocumab) and Kevzara? (sarilumab), which are approved in multiple countries around the world. Regeneron previously used these technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the FDA, and is now being used in efforts to create preventative and therapeutic medicines for COVID-19.

The use of Libtayo to treat advanced NSCLC is investigational and has not been fully evaluated by any regulatory authority.

The open-label, randomized, multi-center Phase 3 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 ≥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, platinum-doublet chemotherapy regimen for four to six cycles (with or without maintenance pemetrexed chemotherapy). The 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 3 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.

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

Libtayo is approved in the U.S., EU, and other countries for adults with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In the U.S., the generic name for Libtayo in its approved indication is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

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