Although Sanofi and Regeneron are not in the current PD-1/PD-L1 market mix they are scrambling to be with Libtayo (cemiplimab) in their quest to capitalize on the profitable lung cancer market. A recent Phase III study was stopped early due to positive results: the trial involving Libtayo versus platinum chemotherapy in a newly diagnosed non-small cell lung cancer (NSCLC) reveals that the drug extended patients’ lives. Libtayo cut the risk of death by 32.4% for those patients whose tumors were associated with PDl-L1 of at least 50%. This data will be the basis of regulatory submissions in the United States and European Union (EU) in 2020.
TrialSite News offers a brief breakdown summary of this recent event.
What is the targeted disease?
Lung cancer—which is the leading cause of cancer death worldwide. In 2020, over 2.2 million new cases are expected to be diagnosed globally. 228,800 new cases will materialize in the United States. About 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. Although 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.
What existing product is Regeneron/Sanofi’s Libtayo going after?
Merck’s Keytruda. The PD-L1 inhibitor
What are immunotherapies? Which ones are used to address NSCLC?
Immunotherapies are designed to boost the body’s natural defense to fight cancer. They use materials made by the body or in a laboratory to improve, target or restore immune system function. An example is the PD-1 pathway—it may be very important in the immune system’s ability to control cancer growth. Blocking the pathway with PD-1 and PD-L1 antibodies has stopped or slowed the growth of NSCLC for some patients. The following drugs are used to block this pathway:
- Atezolizumab (Tecentriq).Roche
- Durvalumab (Imfinzi)/AstraZeneca
- Nivolumab (Opdivo)/BMS
- Pembrolizumab (Keytruda)/Merck
Why did the trial sponsor (in this case Regeneron & Sanofi) stop the trial of Libtayo early?
Because the Independent Data Monitoring Committee to stop the trial early due to the survival benefits observed during the study.
What benefits were observed?
A protocol-specified interim analysis conducted by the IDMC demonstrated that patients treated with Libtayo monotherapy (by itself) had significant increase in overall survival (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 safety signals were identified.
How does this survival figure compare to Merck’s Keytruda?
Keytruda—market leader for NSCLC at present—revealed a 31% reduction in risk of death in those with PD-L1 expression during the Keynote-042 trial. This was the same population currently under study in the Libtayo trial. Again, the Libtayo rate was 34%.
Sizeable Clinical Trial
John Reed, MD, PhD, Global Head of Research and Development at Sanofi, reported, “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. The positive results are extremely encouraging, and we look forward to advancing a potential new treatment option for these patients.”
Who is developing Libtayo?
Both Sanofi and Regeneron under a global collaboration agreement.
A fully-human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By holding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.
The drug is approved in the U.S., European Union 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, as the suffix designated in accordance with Nonproprietary Naming of Biologic Products Guidance for industry issued by the U.S. Food and Drug Administration.
Focus on difficult to treat cancers
The Sanofi/Regeneron partnership are focusing on difficult-to-treat cancers. In skin cancer, this includes a potentially registrational Phase II trial in basal cell carcinoma and additional trials in adjuvant and neoadjuvant CSCC. Libtayo is also being invested in a potentially registrational Phase III in cervical cancer, as well as in trials combining Libtayo with novel therapeutic approaches for both solid tumors and block cancers. These potential uses are investigational and their safety and efficacy have not been evaluated by any regulatory authority.