In an interview with PharmaShots, Dr. Ahmet Sezer, Sanofi’s Peter C. Adamson, and Regeneron’s Israel Lowy shared their views on the US FDA’s approval of Libtayo and the data supporting the approval.
- Regeneron and Sanofi received the US FDA’s approval for Libtayo for the 1L treatment of patients with advanced NSCLC whose tumors have high PD-L1 expression (tumor proportion score ≥50%), as determined by an FDA-approved test
- Libtayo was superior in extending overall survival compared to chemotherapy in a pivotal trial that allowed for certain disease characteristics frequently underrepresented in advanced NSCLC trials. This is the third approval for Libtayo in the US
- Cemiplimab is a fully mAb 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
Answers by Ahmet Sezer, M.D. (Professor in the Department of Medical Oncology at Başkent University in Adana, Turkey)
Tuba: Discuss the study design and the clinical data supporting the approval of Libtayo.
Dr. Sezer: EMPOWER-Lung 1 compared first-line cemiplimab monotherapy versus platinum-based doublet chemotherapy in advanced non-small cell lung cancer, or NSCLC, with PD-L1 expression of at least 50%. The primary endpoints were overall survival and progression-free survival. Secondary endpoints included overall response rate, duration of response, quality of life and safety.
In the trial, cemiplimab reduced the risk of death by 32% among all trial patients and 43% in those with proven PD-L1 expression of at least 50%. And this was achieved with a greater than 70% crossover rate to cemiplimab following disease progression on chemotherapy, as well as the largest population of patients with pretreated and stable brain metastases among advanced NSCLC pivotal trials to date.
Given the highly significant improvement in overall survival, the trial was stopped early and all patients were given the option to receive cemiplimab.
Notably, the trial enrolled patients with disease characteristics that physicians treat in everyday clinical practice, but which are frequently underrepresented in advanced NSCLC trials. 12% of trial patients had pretreated and clinically stable brain metastases, and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation. This gives us new clinical evidence that could enhance our understanding of how to treat advanced NSCLC.
Tuba: Unveil the mechanism of action of Libtayo.
Dr. Sezer: Cemiplimab 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.
Tuba: What does this approval mean to patients, their caregivers, and physicians?
Dr. Sezer: While immunotherapies have transformed the treatment of advanced NSCLC in recent years, there is a continuing need for treatment options for patients with high PD-L1 expression.
Libtayo demonstrated an impressive level of efficacy compared to chemotherapy, significantly extending overall survival with a greater than 70% crossover rate to LIBTAYO following disease progression on chemotherapy.
Additionally, Libtayo was approved based on results from a pivotal trial that allowed for certain disease characteristics frequently underrepresented in pivotal advanced NSCLC trials. This gives doctors important new data when considering LIBTAYO for the varied patients and situations they treat in daily clinical practice.
This advanced NSCLC indication is the third U.S. approval for LIBTAYO and follows a Priority Review by the FDA. LIBTAYO has already changed the treatment paradigm for certain patients with advanced cutaneous squamous cell carcinoma and is poised to do the same for advanced basal cell carcinoma, or BCC. Now, LIBTAYO has the opportunity to make a meaningful difference for many U.S. patients battling advanced NSCLC.
Tuba: Can you put some light on the epidemiology of advanced non-small cell lung cancer?
Dr. Sezer: Lung cancer is the leading cause of cancer death worldwide. In 2020, an estimated 225,000 new cases were diagnosed in the U.S. 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 ≥50% of tumor cells.
Answers by Peter C. Adamson, M.D. (Global Development Head, Oncology and Pediatric Innovation at Sanofi)
Tuba: After BCC, CSCC, and NSCLC, what are other indications in which you are evaluating Libtayo?
Adamson: Our Libtayo clinical program is focused on difficult-to-treat cancers. We expect data from our pivotal trials in advanced cervical cancer and in combination with chemotherapy in advanced NSCLC irrespective of PD-L1 expression later this year, and we are also investigating LIBTAYO in trials in adjuvant and neoadjuvant cutaneous squamous cell carcinoma (CSCC) and in combination with novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.
Tuba: When can we expect EC’s approval of Libtayo and its availability in European countries?
Adamson: The European Medicines Agency is assessing regulatory submissions for Libtayo in advanced NSCLC with ≥50% PD-L1 expression and locally advanced BCC following treatment with a hedgehog pathway inhibitor. Decisions by the European Commission on these submissions are expected in mid-2021. Libtayo is already approved in the EU for the treatment of adults with advanced CSCC that is locally advanced or metastatic and who are not candidates for curative surgery or curative radiation.
Tuba: Discuss in detail about Sanofi and Regeneron’s global collaboration on Libtayo.
Adamson: Libtayo is being jointly developed by Sanofi and Regeneron under a global collaboration agreement.
Answers by Israel Lowy, M.D., Ph.D. (Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron)
Tuba: What is the role of the therapy in improving the lives of patients with advanced NSCLC?
Lowy: PD-1 inhibitors are the standard of care for patients with advanced NSCLC with high PD-L1 expression and no EGFR, ALK, or ROS1 mutations. The recent FDA approval of Libtayo supports our confidence that it has the opportunity to make a meaningful difference for many U.S. patients battling this difficult-to-treat cancer. The EMPOWER-Lung 1 results provide doctors with important new data to help them determine their best treatment approach for the patients they care for in daily clinical practice.
Tuba: How Libtayo is different or better from the other treatment options available in the market?
Lowy: There is still much we don’t know about advanced NSCLC, and the physicians treating it are a data-driven group who appreciate having multiple therapy options. There are no head-to-head trials of LIBTAYO and other PD-1/L1 inhibitors, so we are unable to make direct comparisons. Based on the efficacy and safety demonstrated in EMPOWER-Lung 1, we believe LIBTAYO offers a valuable treatment option that should be considered for appropriate patients with advanced NSCLC with ≥50% PD-L1 expression, per our approved indication. Additionally, EMPOWER-Lung 1 could help to address current gaps in knowledge surrounding advanced NSCLC treatment, as it permitted enrollment of patients with disease characteristics who are frequently underrepresented in clinical trials of advanced NSCLC.
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Ahmet Sezer is a Professor in the Department of Medical Oncology at Başkent University in Adana, Turkey. He specializes in the treatment of patients with lung cancer, including NSCLC. Dr Sezer is a member of the American Society of Clinical Oncology and the European Society of Medical Oncology
Peter C. Adamson is a Global Development Head, Oncology and Pediatric Innovation at Sanofi
Israel Lowy is a Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron