On May 5, 2020 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported topline data from a pivotal, single-arm, open-label trial for the PD-1 inhibitor Libtayo in patients with advanced basal cell carcinoma (BCC) who had progressed on or were intolerant to prior hedgehog pathway inhibitor (HHI) therapy (Press release, Regeneron, MAY 5, 2020, View Source [SID1234557068]). Libtayo demonstrated clinically meaningful and durable responses in this group of patients for whom there are currently no approved treatments. Regeneron and Sanofi plan regulatory submissions in 2020.
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BCC is a skin cancer and is the most common cancer worldwide, with approximately two million new cases diagnosed every year in the U.S. alone. While the vast majority of BCCs are caught early and easily cured with surgery and radiation, a small proportion of tumors can become advanced and penetrate deeper into surrounding tissues (locally advanced), which is more difficult to treat. Approximately 20,000 U.S. patients have advanced BCC, and it is estimated that about 3,000 die each year. BCC marks the second non-melanoma skin cancer for which Libtayo has demonstrated first-in-class data and follows its initial U.S. approval in advanced cutaneous squamous cell carcinoma (CSCC) in 2018.
In the trial, the objective response rate (ORR) for patients (n=84) with locally advanced disease was 29% (95% CI: 19%-40%), with an estimated duration of response (DOR) exceeding one year in 85% of responders. The durable disease control rate (DCR – response or stable disease lasting at least six months) was 60% (95% CI: 48%-70%). In a preliminary analysis of patients (n=28) with metastatic disease, the ORR was 21% (95% CI: 8%-41%), with an estimated DOR exceeding one year in 83% of responders. The durable DCR was 46% (95% CI 28%-66%). All data were assessed by an independent central review. Data are expected to continue to evolve with further follow-up across both patient groups.
"We are very encouraged by these clinically-meaningful response rates and durations of response, which are particularly impressive given this is a second-line setting where there are no approved therapies," Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "These data in advanced BCC provide the third instance where Libtayo monotherapy has demonstrated robust and clinically meaningful outcomes in advanced cancer, and follows last week’s announcement in advanced non-small cell lung cancer where the pivotal trial was stopped early for positive overall survival."
There were no new safety signals in this trial. Among the 132 patients assessed for safety (84 locally advanced and 48 metastatic), 95% experienced an adverse event (AE), 32% had a serious AE and 13% discontinued due to an AE. There were 10 deaths in the locally advanced group and nine deaths in the metastatic group; none of the deaths were considered treatment-related. Regeneron and Sanofi will present additional trial findings at an upcoming medical meeting.
"While PD-1 inhibitors have transformed the outlook for many patients with melanoma, progress for patients with non-melanoma skin cancers has not been as rapid," said Peter C. Adamson, M.D., Global Head of Oncology Development at Sanofi. "We are continuing to address this unmet need by first bringing Libtayo to patients with advanced cutaneous squamous cell carcinoma, and now, with this second trial, as a potential therapy for patients with advanced basal cell carcinoma. These important new results further demonstrate Libtayo’s potential in patients with difficult-to-treat, non-melanoma skin cancers."
In this ongoing, global Phase 2 trial, patients received Libtayo 350 mg intravenously every three weeks for up to 93 weeks or until disease progression, unacceptable toxicity, withdrawal of consent or confirmed complete response. ORR is the primary endpoint and key secondary endpoints include overall survival, progression-free survival, duration of response, safety and quality of life.
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 BCC is investigational and the safety and efficacy have not been evaluated by any regulatory authority.
About Libtayo
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 the first and only immunotherapy 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.
The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. In skin cancer, this includes trials in adjuvant and neoadjuvant CSCC. Libtayo is also being investigated in potentially registrational Phase 3 trials in non-small lung cancer and cervical cancer, as well as in trials combining Libtayo with novel therapeutic approaches for both solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.
IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS
What is Libtayo?
Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.
It is not known if Libtayo is safe and effective in children.
What is the most important information I should know about Libtayo?
Libtayo is a medicine that may treat a type of skin cancer by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended.
Call or see your healthcare provider right away if you develop any symptoms of the following problems or these symptoms get worse:
Lung problems (pneumonitis). Signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain.
Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky or that have blood or mucus; and severe stomach-area (abdomen) pain or tenderness.
Liver problems (hepatitis). Signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual.
Hormone gland problems (especially the adrenal glands, pituitary, thyroid and pancreas). Signs and symptoms that your hormone glands are not working properly may include headaches that will not go away or unusual headaches, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, feeling cold, constipation, deeper voice, very low blood pressure, urinating more often than usual, nausea or vomiting, stomach-area (abdomen) pain, and changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness.
Kidney problems, including nephritis and kidney failure. Signs of these problems may include decrease in your amount of urine, blood in your urine, swelling in your ankles, and loss of appetite.
Skin problems. Signs of these problems may include rash, itching, skin blistering, and painful sores or ulcers in the mouth, nose, throat, or genital area.
Problems in other organs. Signs of these problems may include headache, tiredness or weakness, sleepiness, changes in heartbeat (such as beating fast, seeming to skip a beat, or a pounding sensation), confusion, fever, muscle weakness, balance problems, nausea, vomiting, stiff neck, memory problems, seizures (encephalitis), swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, or eye pain (sarcoidosis), seeing or hearing things that are not there (hallucinations), severe muscle weakness, low red blood cells (anemia), bruises on the skin or bleeding, and changes in eyesight.
Rejection of a transplanted organ. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
Infusion (IV) reactions that can sometimes be severe and life-threatening. Signs of these problems may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, fever, feeling of passing out, back or neck pain, and facial swelling.
Getting medical treatment right away may help keep these problems from becoming more serious.
Your healthcare provider will check you for these problems during your treatment with Libtayo. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may delay or completely stop treatment if you have severe side effects.
Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:
have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus;
have had an organ transplant;
have lung or breathing problems;
have liver or kidney problems;
have diabetes;
are pregnant or plan to become pregnant; Libtayo can harm your unborn baby.
Females who are able to become pregnant:
Your healthcare provider will give you a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
The most common side effects of Libtayo include tiredness, rash, and diarrhea. These are not all the possible side effects of Libtayo. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals and Sanofi at 1-877-542-8296.