On March 29, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Commission (EC) approved Libtayo (cemiplimab) in combination with platinum-based chemotherapy for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with ≥1% PD-L1 expression (Press release, Regeneron, MAR 29, 2023, View Source [SID1234629524]). This includes patients that have no EGFR, ALK or ROS1 aberrations and whose tumors are metastatic or locally advanced and not candidates for definitive chemoradiation.

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"Today’s approval considerably expands the number of people in Europe with advanced non-small cell lung cancer who are eligible for Libtayo-based first-line treatment, including those with PD-L1 expression ranges most commonly seen in real-world practice," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "We are proud that Libtayo continues to distinguish itself among PD-1 pathway blockers, as just one of two PD-1 inhibitors to be approved for use across squamous and non-squamous forms of advanced NSCLC in both combination and monotherapy settings. This marks the fifth approval for Libtayo in Europe."

Lung cancer is the leading cause of cancer death worldwide. In recent years, more than 2.2 million annual new cases have been diagnosed globally. Approximately 80-85% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages.

"The Phase 3 EMPOWER-Lung 3 trial showed significant improvements across primary and key secondary endpoints, including overall survival in the cemiplimab plus chemotherapy arm," said Prof. Martin Reck, Head of Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. "As a treating physician of this patient population, I welcome a new treatment option for patients in Europe, as we continue to strive for better outcomes for patients with advanced non-small cell lung cancer."

"With lung cancer being the leading cause of cancer mortality globally, ongoing research is imperative to find more treatment options for people impacted by this disease," said Anne-Marie Baird, Ph.D., President, Lung Cancer Europe. "This approval highlights continued progress in first-line treatment options for people impacted by advanced lung cancer in Europe."

Libtayo is currently approved in the EU and other countries for the treatment of certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC), advanced NSCLC and advanced cervical cancer. The Libtayo combination was also approved by the U.S. Food and Drug Administration (FDA) for advanced NSCLC regardless of PD-L1 expression in November 2022.

About the Phase 3 Trial
The EC approval is based on data from the global Phase 3 EMPOWER-Lung 3 trial, a randomized, multicenter trial investigating a first-line combination treatment of Libtayo and platinum-doublet chemotherapy (Libtayo combination), compared to platinum-doublet chemotherapy alone. The trial enrolled 466 patients with locally advanced or metastatic NSCLC, as well as squamous or non-squamous histologies across all PD-L1 expression levels and with no EGFR, ALK or ROS1 aberrations. Notably, the trial was designed to closely resemble a patient population with varied disease presentations seen in everyday clinical practice. Among those enrolled, 43% had tumors with squamous histology, 15% had locally advanced disease and 7% had a history of brain metastases.

Patients were randomized 2:1 to receive either Libtayo 350 mg (n=312) or placebo (n=154) administered intravenously every 3 weeks for 108 weeks, plus platinum-doublet chemotherapy administered every 3 weeks for 4 cycles. The trial was stopped early based on a recommendation by the Independent Data Monitoring Committee after the Libtayo combination demonstrated a significant improvement in overall survival (OS). Results of the trial at the primary analysis were published in Nature Medicine in August 2022.

At the primary analysis (median follow-up: 16 months), the trial showed a statistically significant improvement in the primary endpoint of OS for patients treated with the Libtayo combination compared to chemotherapy alone in the overall population (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.53 to 0.93). Among the 70% of patients in the trial expressing PD-L1 ≥1% (n=327), efficacy results for the Libtayo combination arm (n=217) compared to chemotherapy alone (n=110) showed a:

22-month median OS versus 13 months, representing a 45% relative reduction in the risk of death (HR: 0.55; 95% CI: 0.39 to 0.78).
9-month median progression-free survival (PFS) versus 6 months (HR: 0.48; 95% CI: 0.36 to 0.63)
48% objective response rate (ORR) versus 23%
16-month median duration of response (DOR; range: 2 to 19+) versus 5 months (range: 2 to 19+)
At the time of the pre-specified final analysis (median follow up: 28 months), patients with PD-L1 expression ≥1% treated with the Libtayo combination continued to show clinically meaningful survival and PFS benefits compared to chemotherapy alone.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo. Among patients treated with the Libtayo combination evaluated for safety in the trial (n=312), adverse reactions occurring in at least 10% included anemia (44%), alopecia (37%), musculoskeletal pain (27%), nausea (25%), fatigue (23%), peripheral neuropathy (21%), hyperglycemia (18%), decreased appetite (17%), alanine aminotransferase increased (16%), aspartate aminotransferase increased (15%), neutropenia (15%), constipation (14%), dyspnoea (13%), rash (13%), thrombocytopenia (13%), vomiting (12%), diarrhea (11%), insomnia (11%), weight decreased (11%) and hypoalbuminemia (10%). Adverse reactions were serious in 25% of patients and led to permanent discontinuation of the Libtayo combination in 5% of patients.

In December 2022, Libtayo in combination with chemotherapy was added to the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Magnitude of Clinical Benefit Scale (score: 4 out of 5), for patients with advanced NSCLC across squamous and non-squamous histologies, and irrespective of PD-1 expression levels.

About Regeneron in Oncology
At Regeneron, we’re applying more than three decades of scientific innovation with the goal of developing paradigm-changing therapies for patients with cancer. Our oncology portfolio is built around two foundational approaches – our approved PD-1 inhibitor Libtayo and investigational bispecific antibodies – which are being evaluated both as monotherapies and in combination with emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop potentially synergistic treatments for a wide range of solid tumors and blood cancers.

If you are interested in learning more about our clinical trials, please contact us ([email protected] or 844-734-6643) or visit our clinical trials website.