On June 25, 2021 Sanofi and Regeneron reported that The European Commission (EC) has approved its PD-1 inhibitor Libtayo (cemiplimab) for the first-line treatment of adults with non-small cell lung cancer (NSCLC) whose tumor cells have ≥50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations (Press release, Sanofi, JUN 25, 2021, View Source [SID1234584365]). Patients must have metastatic NSCLC or locally advanced NSCLC and not be a candidate for definitive chemoradiation.

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Libtayo is now approved for three advanced cancers in the European Union. The EC also approved Libtayo in advanced basal cell carcinoma, the first treatment to be indicated for those patients who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). In 2019, Libtayo was approved by the EC as the first treatment for adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. Across all of its approved indications, Libtayo had a generally consistent safety profile. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo.

"We are confident that Libtayo has the potential to become an important treatment option for patients in the European Union and thank all the investigators, patients and their families who helped us reach this milestone," said Peter C. Adamson, M.D., Global Development Head, Oncology at Sanofi. "We are anticipating results from our ongoing Phase 3 trial of Libtayo plus chemotherapy in patients with advanced non-small cell lung cancer and remain committed to studying Libtayo in additional cancer settings where there is the potential to improve the outcome for patients."

The EC approval in advanced NSCLC is based on data from a global Phase 3 trial that enrolled 710 patients from 24 countries. The trial, which was one of the largest for a PD-1 inhibitor in advanced NSCLC, was designed to be more reflective of clinical practice by including challenging-to-treat and often underrepresented disease characteristics. Among those enrolled, 12% had pre-treated and clinically stable brain metastases, 44% had squamous cell histology and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation. Furthermore, patients whose disease progressed in the trial were able to change their therapy: those assigned to chemotherapy could crossover to Libtayo treatment, while those assigned to Libtayo monotherapy could continue Libtayo treatment and add four cycles of chemotherapy.

In the overall study population, Libtayo significantly reduced the risk of death by 32% and extended median overall survival (OS) by 8 months compared to chemotherapy, even with 74% of patients crossing over to Libtayo following disease progression on chemotherapy (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.53-0.87; p=0.0022). The median OS was 22 months for Libtayo (range: 18 months to not evaluable) and 14 months for chemotherapy (range: 12 to 19 months). A prespecified analysis of data from patients whose cancers had PD-L1 expression ≥50% (n=563) based on a validated assay was also conducted. As published in The Lancet, Libtayo reduced the risk of death by 43% for patients in this population; median OS was not reached for Libtayo (95% CI: 18 months to not evaluable) and was 14 months for chemotherapy (95% CI: 11 to 18 months).

In the Phase 3 trial, safety was assessed in 697 patients, with a duration of exposure of 27 weeks (range: 9 days to 115 weeks) for the Libtayo group and 18 weeks (range: 18 days to 87 weeks) for the chemotherapy group. Serious adverse reactions (AEs) in at least 2% of patients were pneumonia (5% Libtayo, 6% chemotherapy) and pneumonitis (2% Libtayo, 0% chemotherapy). Treatment was permanently discontinued due to AEs in 6% of Libtayo patients; AEs resulting in permanent discontinuation in at least 2 patients were pneumonitis, pneumonia, ischemic stroke and increased aspartate aminotransferase. No new Libtayo safety signals were observed.

"Libtayo has demonstrated a highly significant improvement in overall survival compared to chemotherapy for patients with advanced non-small cell lung cancer with high PD-L1 expression and a variety of challenging-to-treat disease characteristics," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "Beyond the primary analysis, we continue to conduct post-hoc analyses of our Phase 3 trial with the goal of informing treatment in this patient population."

About the Phase 3 Trial in Advanced NSCLC

EMPOWER-Lung 1 was an open-label, randomized, multi-center Phase 3 trial designed to investigate Libtayo monotherapy compared to platinum-doublet chemotherapy as first-line treatment in patients with advanced NSCLC who tested positive for PD-L1 in ≥50% of tumor cells and had no EGFR, ALK or ROS1 aberrations. PD-L1 expression was confirmed using the Agilent Dako PD-L1 IHC 22C3 pharmDx kit.

The trial randomized 710 patients 1:1 who had either previously untreated metastatic NSCLC (stage IV) or locally advanced NSCLC (stage IIIB/C) who were not candidates for surgical resection or definitive chemoradiation or who had progressed after treatment with definitive chemoradiation. Those receiving Libtayo were intravenously administered 350 mg dose every three weeks for up to 108 weeks, while those receiving chemotherapy received an investigator-selected, platinum-doublet chemotherapy regimen for four to six cycles (with or without maintenance pemetrexed chemotherapy).

The primary endpoints were OS and progression-free survival, and secondary endpoints included objective response rate, duration of response and quality of life. In 2020, the trial was stopped early due to a significant improvement in OS.

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.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Current clinical development programs include Libtayo in combination with chemotherapy for advanced NSCLC irrespective of PD-L1 expression and Libtayo monotherapy for advanced cervical cancer. Libtayo is also being investigated in combination with either conventional or 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.

The generic name for Libtayo in its approved U.S. indications 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 (FDA). Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

On June 25, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported that the European Commission (EC) has approved the PD-1 inhibitor Libtayo (cemiplimab) to treat adults with locally advanced or metastatic basal cell carcinoma (BCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI) (Press release, Regeneron, JUN 25, 2021, View Source [SID1234584366]).

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BCC is the most common type of skin cancer worldwide, representing up to 80% of non-melanoma skin cancers, and incidence is increasing across many European countries. While the large majority of BCCs are caught early and easily cured with surgery and/or radiation, a small proportion of cases can develop into advanced BCC and penetrate deeper into surrounding tissues (locally advanced) or spread to other parts of the body (metastatic), becoming more difficult to treat.

"Libtayo is the first immunotherapy to show a clinical benefit in patients with advanced BCC after HHI therapy in a pivotal trial, and with this first-in-class approval has the potential to transform treatment for patients in Europe whose cancer has progressed despite HHI treatment," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "We look forward to continuing to investigate this medicine in additional settings, with the goal of helping more patients with difficult-to-treat cancers around the world."

Libtayo is now approved for three advanced cancers in the European Union, following the EC’s concurrent approval of Libtayo for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumor cells have ≥50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations. In 2019, Libtayo was approved by the EC as the first treatment for adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. Across all of its approved indications, Libtayo had a generally consistent safety profile. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo.

The EC approval in BCC is based on data from the largest prospective clinical trial (n=119) in patients with advanced BCC previously treated with an HHI to date. Libtayo-treated patients with locally advanced BCC experienced an objective response rate (ORR) of 32% (95% confidence interval [CI]: 22-43) (25% partial response, 7% complete response) by independent central review. Libtayo-treated patients with metastatic BCC demonstrated an ORR of 29% (95% CI: 15-46) (26% partial response, 3% complete response) by investigator assessment. In addition, approximately 90% of patients across both groups had a duration of response (DOR) of 6 months or longer per Kaplan Meier estimates, and the median DOR has not been reached for either group. Median duration of follow-up was 16 months for locally advanced BCC and 9 months for metastatic BCC.

Safety was assessed in 816 patients across all four Libtayo monotherapy pivotal trials in its approved indications. Adverse events were serious in 30% of patients and led to permanent discontinuation in 8% of patients. Immune–related adverse reactions occurred in 22% of patients and led to permanent discontinuation in 4% of patients. The most common immune-related adverse reactions were hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin adverse reactions (2%).

"Since its launch in Europe just two years ago, Libtayo has redefined the standard of care for advanced CSCC and has the potential to do the same in advanced BCC," said Peter C. Adamson, M.D., Global Development Head, Oncology at Sanofi. "Together with Regeneron, we’re committed to addressing gaps in the treatment of advanced forms of non-melanoma skin cancer."

About the Phase 2 Trial in Advanced BCC

The EC approval was based on data from an ongoing open-label, multi-center, non-randomized Phase 2 trial of patients with unresectable locally advanced BCC or metastatic BCC (nodal or distant). Patients in both cohorts had either progressed on HHI therapy, had not had an objective response after nine months on HHI therapy, or were intolerant of prior HHI therapy. The primary efficacy endpoint was confirmed ORR, and a key secondary endpoint was DOR, assessed by independent central review.

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.

The recommended dose of Libtayo is 350 mg administered as an intravenous infusion over 30 minutes every three weeks, until disease progression or unacceptable toxicity. Libtayo is available as a single-dose 350 mg vial. No PD-L1 or tumor mutational burden (TMB) testing is required before starting treatment with Libtayo for advanced BCC.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Current clinical development programs include Libtayo in combination with chemotherapy for advanced NSCLC irrespective of PD-L1 expression and Libtayo monotherapy for advanced cervical cancer. Libtayo is also being investigated in combination with either conventional or 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.

The generic name for Libtayo in its approved U.S. indications 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 (FDA). Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

About Regeneron’s VelocImmune Technology

Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately a quarter of all original, FDA-approved fully human monoclonal antibodies currently available. This includes REGEN–COV (casirivimab and imdevimab), Dupixent (dupilumab), Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb) and Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn).

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.

Libtayo is a prescription medicine used to treat people with a type of skin cancer called basal cell carcinoma that cannot be removed by surgery (locally advanced BCC) and have received treatment with an HHI, or cannot receive treatment with an HHI.

Libtayo is a prescription medicine used to treat people with a type of skin cancer called basal cell carcinoma that has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with an HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.

Libtayo is a prescription medicine used to treat people with a type of lung cancer called non-small cell lung cancer (NSCLC). Libtayo may be used as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high "PD-L1" and your tumor does not have an abnormal "EGFR", "ALK "or "ROS1" gene.

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 certain cancers 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. You can have more than one of these problems at the same time. 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 new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, or chest pain
Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness
Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal
Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite
Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes
Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with Libtayo. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising
Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: nausea, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling
Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Libtayo. Your healthcare provider will monitor you for these complications.
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 also need to delay or completely stop treatment with Libtayo 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 received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
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 muscle or bone pain, 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.

Please see full Prescribing Information, including Medication Guide.

On June 25, 2021 Prescient Therapeutics Limited (ASX:PTX) reported that it has successfully completed the manufacturing and delivery of crucial components for its unique, next-generation OmniCAR platform (Press release, Prescient Therapeutics, JUN 25, 2021, View Source;utm_medium=rss&utm_campaign=prescient-therapeutics-reaches-a-major-car-t-manufacturing-milestone [SID1234584383]).

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The two novel components of the OmniCAR platform are: the SpyTagged binders and CAR-T cells expressing SpyCatcher. Notably, the SpyTag/SpyCatcher system is a crucial technology for binding of proteins. SpyCatcher is a genetically encoded protein, which reacts with SpyTag, a peptide of 13 amino acids, forming a bond between the two.

WATCH NOW: Expert Talks With Mr Steven Yatomi Clarke, CEO and Managing Director of Prescient Therapeutics

Delivery of binders and lentiviral vectors
The Company disclosed that a range of binders against various cancer targets, including CLL-1, CD33, EGFRviii, and Her2, have been manufactured by a US-based antibody manufacturer. More importantly, Prescient has incorporated SpyTag into these binders for the Company’s three next-gen CAR-T programs. SpyTag is necessary for covalent binding to immune cells (for instance, T-cells) in the OmniCAR system.

Source: PTX Update, 24 June 2021

Besides binders, Prescient has also obtained the delivery of lentiviral vectors. Lentiviral vectors are viruses which are used as gene delivery vehicle as they help in inserting, tweaking, or deleting a particular gene in a cell or organism.

As highlighted by PTX, lentiviral vectors are a rate-limiting step in CAR-T production and will be used to produce CAR-T cells expressing SpyCatcher.

Together, the SpyTagged binders and SpyCatcher CAR-T cells establish the basis for Prescient’s unique, modular OmniCAR platform.

The binders and lentiviral vectors have been delivered to the Peter MacCallum Cancer Centre, or Peter Mac, in Melbourne for construct assessment as well as in vivo and in vitro development.

On June 25, 2021 Abbott (NYSE: ABT) reported that it will announce its second-quarter 2021 financial results on Thursday, July 22, 2021, before the market opens (Press release, Abbott, JUN 25, 2021, View Source [SID1234584349]).

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The announcement will be followed by a live webcast of the earnings conference call at 8 a.m. Central time (9 a.m. Eastern), and will be accessible through Abbott’s Investor Relations website at www.abbottinvestor.com. An archived edition of the call will be available later that day.

On June 24, 2021 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company primarily focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients,reported that it will present its oropharyngeal cancer (OPC) patient population analysis of the Phase 2 Validive (clonidine HCl MBT) trial for the prevention of chemoradiotherapy-induced severe oral mucositis in head and neck cancer at the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) 2021 annual meeting (Press release, Monopar Therapeutics, JUN 24, 2021, View Source [SID1234584318]). This analysis provided the rationale for the design of Monopar’s Phase 2b/3 VOICE trial, which is open and accruing oropharyngeal cancer patients in the US.

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"We are excited to share the data from our analysis at this pre-eminent multidisciplinary conference dedicated to supportive care in cancer and for the opportunity to continue working towards providing a treatment for this debilitating condition," said Andrew Mazar, PhD, Chief Scientific Officer of Monopar.

Session Title: Mucositis – New Dimensions in Research and Clinical Practice, Oral Proffered Paper 2

Presentation Title: Subgroup Analysis of Head and Neck Cancer Patients Treated with Clonidine Mucobuccal Tablet in a Randomized, Double-Blind Phase 2 Trial (Study BA2009-28-01) Supports Further Clinical Development in Patients with Oropharyngeal Cancer

Author: Andrew Mazar, PhD, Chief Scientific Officer of Monopar Therapeutics

Date and Time: The Company’s presentation will be available on demand for registered attendees starting Friday, June 25, 2021 at 8:00am EDT. For information on registration, visit: View Source

About Validive

Validive (clonidine mucobuccal tablet; clonidine MBT) is a novel mucobuccal tablet (MBT) formulation. The mucobuccal tablet provides for prolonged and enhanced local delivery of clonidine to the regions of oral mucosal radiation damage in OPC patients. The tablet is self-administered once daily in the patient’s home setting with the patient placing it under the upper lip where it adheres to the gums and dissolves over several hours, continuously releasing clonidine into the saliva. Clonidine agonizes the alpha-2 adrenergic receptor on macrophages (white blood cells present in the immune tissues of the oropharynx), decreasing the macrophages’ expression of the destructive cytokines that are released in response to radiotherapy. A completed double-blind, randomized, placebo-controlled Phase 2 clinical trial of Validive showed reduced incidence compared to placebo (absolute decrease of 26%, relative decrease of 40%) in OPC patients treated with Validive 100 µg, a safety profile similar to placebo, and a high rate of treatment compliance (over 90%).