On May 29, 2020 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported new, longer-term data for PD-1 inhibitor Libtayo (cemiplimab-rwlc) from a pivotal Phase 2 trial in advanced cutaneous squamous cell carcinoma (CSCC), the deadliest non-melanoma skin cancer (Press release, Regeneron, MAY 29, 2020, View Source [SID1234558765]). These results demonstrate both longer durability and higher complete response (CR) rates than previously reported. Furthermore, the data make up part of the largest and most mature prospective clinical dataset in patients with metastatic CSCC (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or radiation. The data were presented during the virtual 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
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"The three-year follow-up data demonstrate significant long-term outcomes with Libtayo, which is now standard-of-care for patients with advanced CSCC in many countries," said Dr. Danny Rischin, Director, Department of Medical Oncology at Peter MacCallum Cancer Centre, Victoria, Australia. "The Libtayo data on duration of response and overall survival provide new insights into the longer-term treatment of advanced CSCC, with the median still not reached for either measure. Remarkably, it is exciting to see the number of complete responses increase with longer follow-up, which reinforces the potential ongoing benefit of Libtayo treatment in this aggressive skin cancer."
With up to three years of follow-up, results from the pivotal Phase 2 trial showed 46% of patients (95% CI: 39%-53%) experienced substantial tumor shrinkage following Libtayo treatment, with a median time to response of 2 months (interquartile range: 2-4 months). Furthermore, more patients (16%) saw their tumors disappear completely over time compared to previous analyses. Among patients with metastatic disease who had the longest available follow-up (Group 1 in table below), 20% of patients have now achieved a CR, increasing from 7% in the 2017 primary analysis. Among patients who achieved a CR in any group, median time to CR was 11 months (interquartile range: 7-15 months). Median overall survival and median duration of response have yet to be reached for any treatment group.
Results by treatment group were as follows:
Group 1:
mCSCC
3 mg/kg every
2 weeks
(n=59)
Group 2:
laCSCC
3 mg/kg every
2 weeks
(n=78)
Group 3:
mCSCC
350 mg every
3 weeks
(n=56)
Total
(n=193)
Median duration of follow-up (range)
19 months
(1–36)
16 months
(1–36)
17 months
(1–26)
16 months
(1–36)
Objective response rate (95% confidence interval [CI])
51%
(38%–64%)
45%
(34%–57%)
43%
(30%–57%)
46%
(39%–53%)
CR (n)
20%
(12)
13%
(10)
16%
(9)
16%
(31)
Partial response (n)
31%
(18)
32%
(25)
27%
(15)
30%
(58)
Median observed time to response (interquartile range)*
2 months
(2–2)
2 months
(2–4)
2 months
(2–4)
2 months
(2–4)
Median observed time to CR (interquartile range)
11 months
(7–18)
10 months
(7–13)
12 months
(8–17)
11 months
(7–15)
Median duration of response (95% CI)*
Not reached
(21, NE)
Not reached
(18, NE)
Not reached
(NE, NE)
Not reached
(29, NE)
Median overall survival
Not reached
Not reached
Not reached
Not reached
NE = not evaluable
*Based on number of patients with confirmed complete or partial response and Kaplan-Meier estimation.
CR rates over time were as follows:
Group 1:
mCSCC
3 mg/kg every
2 weeks
Group 2:**
laCSCC
3 mg/kg every
2 weeks
Group 3:
mCSCC
350 mg every
3 weeks
Primary analysis, CR % (n)
7%
(4)
13%
(10)
5%
(3)
Approximately 1 year of follow-up, CR % (n)
17%
(10)
13%
(10)
16%
(9)
Approximately 2 years of follow-up, CR % (n)
20%
(12)
NE
NE
**Among 23 laCSCC patients who were included in the pre-specified Group 2 interim analysis, there were no CRs.
No new safety signals were identified. The most common treatment-emergent adverse events (AEs) were fatigue (35%), diarrhea (28%) and nausea (24%). The most common grade 3 or higher treatment-related AEs were pneumonitis (3%), autoimmune hepatitis (2%), anemia, colitis and diarrhea (each 1%). No new AEs resulting in death were reported compared to previous reports.
In addition to the updated efficacy and safety data, a separate post-hoc analysis of health-related quality of life (HRQL) outcomes from the Phase 2 trial was presented for the first time. A significant majority (91%) of patients reported improved or stable overall HRQL and 43% of patients experienced a clinically meaningful reduction in pain by the end of the assessment period. The analysis was based on patient responses to the European Platform of Cancer Research cancer specific 30-item HRQL questionnaire (QLQ-C30).
The open-label, single-arm, global, pivotal Phase 2 trial (Study 1540) enrolled 193 patients with laCSCC or mCSCC who were not candidates for curative surgery or radiation. The initial primary analysis of the trial, along with results from a Phase 1 trial (Study 1423), supported the U.S. Food and Drug Administration (FDA) approval of Libtayo in late 2018. Together, the trials represent the largest and most mature prospective clinical dataset in advanced CSCC.
Libtayo is being jointly developed 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.
About CSCC
CSCC is the second most common type of skin cancer in the world, accounting for approximately 20% of all skin cancers, and the number of newly diagnosed cases is expected to rise substantially in many countries. Although CSCC has a good prognosis when caught early, the cancer can prove especially difficult to treat effectively when it is advanced, and patients can experience reduced quality of life due to the impact of the disease as it progresses. While estimates vary, sources suggest that 7,000 patients in the U.S. die annually of advanced CSCC, which is comparable to the number of deaths caused by melanoma.
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 mCSCC or laCSCC 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 a pivotal trial in advanced basal cell carcinoma and additional trials in adjuvant and neoadjuvant CSCC. Libtayo is also being investigated in pivotal Phase 3 trials in non-small cell 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 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.
For more information, please see full Prescribing Information, including Medication Guide.
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.