On May 19, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported the company will share a range of presentations for its PD-1 inhibitor Libtayo (cemiplimab-rwlc) and broader oncology portfolio at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 4-8, taking place virtually (Press release, Regeneron, MAY 19, 2021, View Source [SID1234580258]). Presentations include new clinical data and in-depth analyses on the impact of Libtayo in several advanced cancers, including non-small cell lung cancer (NSCLC), cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC) and melanoma.

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"Following our presentation of updated, positive cervical data at the ESMO (Free ESMO Whitepaper) Virtual Plenary, we look forward to providing an overview of the maturing experience with Libtayo across a range of cancers at ASCO (Free ASCO Whitepaper)," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology, at Regeneron. "Presentations include a new post-hoc analysis of our pivotal Libtayo trial for advanced non-small cell lung cancer in a subset of patients with brain metastases, as well as new data from a prospective real-world trial in immunocompromised or immunosuppressed patients with advanced cutaneous squamous cell carcinoma. We will also share presentations showing the impact of Libtayo on quality of life in multiple cancers, and for the first time, positive results for Libtayo in combination with our investigational LAG-3 inhibitor fianlimab in advanced melanoma."

Investigator-assessed results from two expansion cohorts of a Phase 1 trial investigating fianlimab (REGN3767) and Libtayo in advanced melanoma were published by ASCO (Free ASCO Whitepaper) today. Efficacy was greatest in PD-1 inhibitor naïve patients, who experienced a 64% objective response rate (21 of 33 patients; 3 complete responses, 18 partial responses), and the median progression-free survival and median duration of response had not yet been reached.

Among 48 patients receiving the fianlimab and Libtayo combination, the most common adverse events (AEs) were fatigue (n=15; 31%) and rash (n=11; 23%). Grade 3 or higher AEs occurred in 35% (n=17) of patients, with 23% (n=11) of these events classified as serious. Treatment discontinuations due to an AE occurred in 8% (n=4) of patients. Updated efficacy and safety data will be presented during a poster discussion session available on-demand starting Friday, June 4 at 9:00 a.m. ET (Abstract 9515).

Earlier this year, Libtayo monotherapy was approved in the U.S. for certain patients with NSCLC whose tumors have high PD-L1 expression and no EGFR, ALK or ROS1 aberrations. The FDA also recently approved the use of Libtayo as the first immunotherapy indicated for patients with BCC previously treated with a hedgehog pathway inhibitor (HHI) or for whom an HHI is not appropriate, whose cancer is either locally-advanced (full approval) or metastatic (accelerated approval). In 2018, Libtayo was approved as the first systemic treatment for certain patients with advanced CSCC. Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

Investor Webcast Information
Regeneron will host a conference call and simultaneous webcast to share updates on the Company’s oncology portfolio on Monday, June 7 at 4:30 p.m. ET. To access this call, dial (888) 660-6127 (U.S.) or (973) 890-8355 (International), conference ID 7569618. A link to the webcast may be accessed from the ‘Investors and Media’ page of Regeneron’s website at View Source A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.

Libtayo joint presentations with Sanofi at ASCO (Free ASCO Whitepaper)
NSCLC

Cemiplimab monotherapy as first-line (1L) treatment of patients with brain metastases from advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%; EMPOWER-Lung 1 subgroup analysis (Abstract 9085; Mustafa Özgüroğlu, M.D.; Poster Session)
Patient-reported symptoms, functioning, and quality of life (QoL) in patients treated with cemiplimab monotherapy for first-line treatment of advanced NSCLC with PD-L1 ≥50%: Results from EMPOWER-Lung 1 study (Abstract 9078; Mahmut Gümüş, M.D.; Poster Session)
Network meta-analysis (NMA) of immuno-oncology (IO) monotherapy (mono) as first-line (1L) treatments (txs) for advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50% (Abstract e21091; Nick Freemantle, Ph.D.; Online Publication)
Budget impact (BI) analysis of cemiplimab for first-line (1L) advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50% in the United States (Abstract e18817; Andreas Kuznik, Ph.D.; Online Publication)
BCC

Health-related quality of life (HRQoL) in patients (pts) with locally advanced basal cell carcinoma (laBCC) treated with cemiplimab: analysis of a phase II, open-label clinical trial (Abstract 9566; Alexander J. Stratigos, M.D.; Poster Session)
Frequency, characteristics, and subsequent treatment (Tx) of real-world patients (pts) who discontinue hedgehog inhibitors (HHI) as first-line (1L) systemic Tx for advanced basal cell carcinoma (aBCC) (Abstract e18740; C. Lance Cowey, M.D.; Online Publication)
Outcomes in patients (pts) with advanced basal cell carcinoma (aBCC) who discontinued hedgehog inhibitors (HHI) as first-line (1L) systemic treatment (Tx) in a US community oncology setting: A retrospective observational study (Abstract e18742; C. Lance Cowey, M.D.; Online Publication)
Budget impact (BI) analysis of cemiplimab-rwlc for advanced basal cell carcinoma (BCC) after hedgehog inhibitor (HHI) therapy in the United States (Abstract e18830; Eleanor Paul; Online Publication)
CSCC

Checkpoint inhibition in immunosuppressed or immunocompromised patients with advanced cutaneous squamous cell carcinoma (CSCC): Data from prospective CemiplimAb-rwlc Survivorship and Epidemiology (C.A.S.E.) study (Abstract 9547; Guilherme Rabinowits, M.D.; Poster Session)
Additional Regeneron presentations at ASCO (Free ASCO Whitepaper)
Libtayo in combination with fianlimab

Clinical activity of fianlimab (REGN3767), a human anti-LAG-3 monoclonal antibody, combined with cemiplimab (anti-PD-1) in patients (pts) with advanced melanoma (Abstract 9515; Omid Hamid, M.D.; Poster Discussion)
REGN5668 (MUC16xCD28)

A Phase I/II, multicenter, open-label study of REGN5668 (mucin [MUC]16 x CD28 bispecific antibody [bsAb]) with cemiplimab (programmed death [PD]-1 Ab) or REGN4018 (MUC16 x CD3 bsAb) in recurrent ovarian cancer (rOVCA) (Abstract TPS5602; Ira Winer, M.D., Ph.D.; Trial-in-progress Poster)
The use of fianlimab in combination with Libtayo for advanced melanoma is investigational, and its safety and efficacy have not been evaluated by any regulatory authority.

About Regeneron in Oncology
At Regeneron, we’re applying more than three decades of scientific innovation to develop paradigm-changing therapies for patients with cancer. Fusing our deep expertise in biology with our proprietary VelociSuite technologies, we have contributed landmark cancer research to the field and are pioneering first-in-class investigational treatments through a growing pipeline of more than 10 cancer therapies.

Our oncology portfolio is built around two foundational approaches – our approved PD-1 inhibitor Libtayo and bispecific antibodies – which are being investigated both as monotherapies and in combination with emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic treatments for a wide range of solid tumors and blood cancers.

For more information on our clinical programs, visit www.regeneron.com/pipeline.

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 currently approved as the first systemic treatment in the U.S., EU and other countries for adults with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In the U.S., Libtayo is also approved as the first immunotherapy indicated for patients with advanced BCC previously treated with an HHI or for whom an HHI is not appropriate, and for the first-line treatment of certain patients with advanced NSCLC with ≥50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations.

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 FDA.

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.

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 co-Founder, 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 with 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.

On May 19, 2021 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts evaluating several products in the company’s portfolio, or created using Genmab’s innovation, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held virtually June 4-8, and at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress, being held virtually June 9-17 (Press release, Genmab, MAY 19, 2021, View Source [SID1234580275]). The presentations will include clinical data evaluating the investigational bispecific antibody epcoritamab (DuoBody-CD3xCD20) in patients with Non-Hodgkin Lymphoma (NHL), several studies evaluating Janssen Biotech, Inc. (Janssen)’s daratumumab and the subcutaneous formulation of daratumumab, and multiple abstracts evaluating Janssen’s bispecific program, which leverages Genmab’s DuoBody technology platform. In addition, trial-in-progress (TiPs) summaries of phase 3 trials evaluating epcoritamab and the investigational antibody-drug conjugate (ADC) tisotumab vedotin in patients with cervical cancer will be presented.

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All the abstracts have been published on the ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) websites and may be accessed online via the ASCO (Free ASCO Whitepaper) Meeting Library and the EHA (Free EHA Whitepaper) Open Access Library.

Epcoritamab is being co-developed by Genmab and AbbVie (NYSE: ABBV). Tisotumab vedotin is being co-developed by Genmab and Seagen Inc. (Nasdaq: SGEN), under an agreement in which the companies share all costs and profits for the product on a 50:50 basis. Daratumumab is being developed by Janssen under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab, and the companies have a collaboration to create and develop bispecific antibodies using Genmab’s DuoBody technology platform.

"The breadth and depth of the data being presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) demonstrate Genmab’s dedication to creating and developing a comprehensive portfolio of innovative and differentiated antibody medicines with the goal of improving the lives of people with cancer and their families," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We will continue to progress the investigational products in our pipeline, alone and together with our partners, to deliver new therapeutic options to patients in need."

Abstracts accepted for presentation at ASCO (Free ASCO Whitepaper) include:

Epcoritamab (DuoBody-CD3xCD20):

Subcutaneous Epcoritamab in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: Safety Profile and Anti-tumor Activity
Phase 3 Trial (GCT3013-05) of Epcoritamab Versus Standard of Care in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Tisotumab vedotin

Tisotumab Vedotin vs Investigator’s Choice Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical Cancer (innovaTV 301/ENGOT‑cx12/GOG 3057, Trial in Progress)

Daratumumab:

Subcutaneous Daratumumab + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Patients With Newly Diagnosed Light Chain (AL) Amyloidosis: Updated Results From the Phase 3 ANDROMEDA Study
Daratumumab (DARA) Maintenance or Observation (OBS) After Treatment With Bortezomib, Thalidomide and Dexamethasone (VTd) With or Without DARA and Autologous Stem Cell Transplant (ASCT) in Patients (pts) With Newly Diagnosed Multiple Myeloma (NDMM): CASSIOPEIA Part 2
Abstracts accepted for presentation at EHA (Free EHA Whitepaper) include:

Epcoritamab (DuoBody-CD3xCD20):

Subcutaneous Epcoritamab in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: Safety Profile and Anti-tumor Activity

Daratumumab:

Subcutaneous Daratumumab + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Patients With Newly Diagnosed Light Chain (AL) Amyloidosis: Updated Results From the Phase 3 ANDROMEDA Study
Daratumumab (DARA) Maintenance or Observation (OBS) After Treatment With Bortezomib, Thalidomide and Dexamethasone (VTd) With or Without DARA and Autologous Stem Cell Transplant (ASCT) in Patients (pts) With Newly Diagnosed Multiple Myeloma (NDMM): CASSIOPEIA Part 2
Phase 3 Study of Daratumumab, Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Asian Patients with Newly Diagnosed Multiple Myeloma (NDMM): OCTANS

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to tumors to elicit an immune response towards malignant cells. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T cell mediated killing of lymphoma B cells.1 CD20 is a clinically validated therapeutic target, and is expressed on many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.2,3 Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

About Tisotumab Vedotin
Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab’s fully human monoclonal antibody specific for tissue factor and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a cell-surface protein and associated with tumor growth, angiogenesis, metastasis and poor prognosis.4 Based on its elevated expression in multiple solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

Tisotumab vedotin is being evaluated in a global phase 3, randomized clinical trial innovaTV 301, versus investigator’s choice of chemotherapy in recurrent or metastatic cervical cancer. The primary endpoint is overall survival and secondary endpoints include progression-free survival, duration of response, objective response rate, safety and tolerability. Enrollment is ongoing and the study is intended to support global registrations. In addition, tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in recurrent or metastatic cervical cancer, ovarian cancer, and other solid tumors and in combination with commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three-week dosing schedule. More information about the innovaTV 301 clinical trial, including enrolling sites, as well as other ongoing clinical trials is available at www.clinicaltrials.gov.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) has become a backbone therapy in the treatment of multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with carfilzomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy; in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.5 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.6 Daratumumab is the first subcutaneous CD38 antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with newly diagnosed light-chain (AL) amyloidosis in combination with bortezomib, cyclophosphamide, and dexamethasone. It is also approved in the U.S. for the treatment of adult patients with multiple myeloma: in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for ASCT; in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology. DARZALEX FASPRO is the first subcutaneous CD38 antibody approved in the U.S. for the treatment of multiple myeloma and the first and only approved treatment for patients with AL amyloidosis in the U.S.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).5,8,9,10,11

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

On May 19, 2021 Aileron Therapeutics (NASDAQ:ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported that it will host a key opinion leader (KOL) investor event focused on the topic of protecting cancer patients from chemotherapy-induced toxicities on Wednesday, May 26, 2021 at 11:00 am ET (Press release, Aileron Therapeutics, MAY 19, 2021, View Source [SID1234580291]).

Schedule your 30 min Free 1stOncology Demo!
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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The fireside chat, moderated by Soumit Roy, Ph.D., Managing Director at JonesTrading, will feature Alan List, M.D. and Lodovico Balducci, M.D., discussing the unmet need in addressing chemotherapy-induced toxicities, the resulting medical impact and quality-of-life burden on cancer patients, as well as the opportunity for a new paradigm known as chemoprotection that focuses on proactive prevention.

Dr. List is a hematologist and physician scientist who is internationally recognized for his many contributions in the development of more effective treatment strategies for myeloid and other malignancies. He is the author of more than 450 peer-reviewed manuscripts, chapters and books, and is the former President and CEO of Moffitt Cancer Center, and past president of the Society of Hematologic Oncology. Currently, Dr. List serves as Chief Medical Officer at Precision Biosciences. Dr. Balducci, a renowned geriatric oncologist, was formerly a Senior Member of the Senior Adult Oncology Program and Medical Director of Affiliates & Referring Physician Relations at Moffitt Cancer Center, and Professor of Oncologic Sciences, University of South Florida College of Medicine, in Tampa, Florida.

A webcast of the event will be available under the Investors and Media section on Aileron’s website at View Source A replay of the webcast will be archived on Aileron’s website for 90 days following the event.

To register for the event, please click here.

Aileron’s first-in-class dual MDM2/MDMX inhibitor, ALRN-6924, is currently in clinical development as a therapeutic agent designed to deliver selective chemoprotection for patients with p53-mutated cancers. 50% of all cancer patients have p53-mutated cancer.

ALRN-6924 has demonstrated a protective effect against chemotherapy-induced bone marrow toxicities, including neutropenia, thrombocytopenia and anemia, in a Phase 1b trial in patients with p53-mutated small cell lung cancer (SCLC) undergoing treatment with topotecan in second line of therapy. In the second quarter of 2021, Aileron plans to initiate a Phase 1b randomized, placebo-controlled trial of ALRN-6924 in patients with p53-mutated non-small cell lung cancer (NSCLC) who are receiving first-line carboplatin plus pemetrexed (with or without immune checkpoint inhibitors).

On May 19, 2021 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that primary analysis data from the Phase 2 OPTIC (Optimizing Ponatinib Treatment In CML) trial will be presented during an oral session at the virtual 57th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and as an oral session at the virtual 26th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting (Press release, Takeda, MAY 19, 2021, View Source [SID1234580307]). The OPTIC trial is a randomized, open-label study prospectively evaluating response-based dosing regimens of ICLUSIG (ponatinib) over a range of three starting doses (45-, 30-, or 15-mg) with the aim of optimizing its efficacy and safety in patients with chronic-phase chronic myeloid leukemia (CP-CML) who are resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy.

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"The OPTIC data, along with the recently updated U.S. FDA indication, demonstrate the benefit ICLUSIG can offer as a third-generation TKI."

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The OPTIC trial, which evaluated treatment in patients with resistant disease, with and without mutations, met its primary endpoint. The study demonstrates that the optimal benefit-risk profile for ICLUSIG in patients with CP-CML is achieved with a daily starting dose of 45-mg and, upon achieving ≤1% BCR-ABL1IS, dose reduction to 15-mg. The results also suggest a clinically manageable safety and arterial occlusive event (AOE) profile for ICLUSIG.

"The primary analysis of the OPTIC data reinforce that ICLUSIG is very valuable in the management of patients with resistant and intolerant chronic-phase CML. ICLUSIG should be considered following failure of two or more TKIs. This approach minimizes the need to use back-to-back second-generation TKIs, which is usually associated with low probability of response and poor outcomes," said Jorge Cortes, MD, Georgia Cancer Center at Augusta University, and an OPTIC trial principal investigator. "These findings further demonstrate that the optimal ICLUSIG benefit-risk profile can be achieved with a response-based dosing regimen, providing efficacy while reducing risk for arterial occlusive events."

The first presentation of OPTIC data at the 56th ASCO (Free ASCO Whitepaper) and the 25th EHA (Free EHA Whitepaper) virtual Annual Meetings in 2020 showcased revised benefit-risk outcomes of ICLUSIG from the interim analysis (cutoff date of July 2019), which evaluated 216 patients with a median follow-up of 21 months. The primary analysis evaluated 283 patients with a median follow-up time of 32 months, reinforcing the positive and prolonged duration of response in this resistant CP-CML patient population while maintaining a manageable safety profile at a longer follow-up period.

"There is a misconception that chronic-phase CML is a ‘good cancer’ due to the fact it can be well controlled, but for patients with resistant and intolerant disease, continued investigation and treatment options are critical. The primary analysis of OPTIC solidifies our understanding of how ICLUSIG can address gaps in care for these patients," said Christopher Arendt, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. "The OPTIC data, along with the recently updated U.S. FDA indication, demonstrate the benefit ICLUSIG can offer as a third-generation TKI."

In December 2020, the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for ICLUSIG based on the OPTIC data. The updated label includes an expanded indication for adult patients with CP-CML that is resistant or intolerant to at least two prior kinase inhibitors, as well as the optimized response-based dosing regimen.

OPTIC Primary Analysis: A Dose-Optimization Study of Three Starting Doses of Ponatinib (PON).

Key findings, to be presented by Dr. Jorge Cortes, include:

By the primary analysis (cutoff date of May 2020) with median follow-up time of 32 months, 100% of patients in the OPTIC trial were evaluable for the primary endpoint.
The maximum rates of ≤1% BCR-ABL1IS at 12 months were achieved in the 45-mg/day starting dose cohort (44.1%), and 73.3% of patients in this cohort maintained responses with the dose reduction to 15-mg/day. 30-mg/day and 15-mg/day cohorts also demonstrated benefit (29% and 23%, respectively), especially in patients with less-resistant disease and without the T315I mutation.
Positive survival outcomes were observed in all three arms, with an 89% 36-month overall survival (OS) probability anticipated for the 45-mg starting dose cohort and 73% progression-free survival (PFS) anticipated for the same cohort.
This indicates the dose-reduction strategy did not impact overall survival regardless of prior second-generation TKI resistance or the presence of BCR-ABL1 mutations.
Rates of arterial occlusive events (AOEs) observed at the time of primary analysis (6% overall and 9.6% in the 45-mg cohort) suggest a clinically manageable safety and AOE profile.
Safety data include:
Among all patients (N=283), the most common treatment emergent adverse events (TEAEs) Grade 3 or greater were thrombocytopenia (27%), neutropenia (17%) and anemia (7%).
Reported AOEs were 10%, 5% and 3% for the 45-, 30-, 15-mg/day starting dose cohorts, respectively. Grade 3 or greater AOEs were 5%, 5% and 3% for the 45-, 30-, 15-mg/day starting dose cohorts, respectively.
Reported serious AOEs were 4%, 4% and 3% for the 45-, 30-, 15-mg/day starting dose cohorts, respectively. There were 4 deaths related to AEs (2 sudden deaths and 2 pneumonia).
Learn more about Takeda Oncology’s presence at this year’s ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) annual meetings. Takeda will host a webcast for analysts and investors on Tuesday, June 8, at 6:30 p.m. ET to discuss these and other data being presented at ASCO (Free ASCO Whitepaper), and to provide an update on the oncology pipeline. Please contact [email protected] for further details. Presentation slides and an archived replay of the webcast will be available at View Source

About the OPTIC Trial

OPTIC (Optimizing Ponatinib Treatment In CML) is an ongoing randomized, dose-ranging trial designed to evaluate three starting doses of ICLUSIG (45-, 30-, and 15-mg) in patients with resistant chronic-phase chronic myeloid leukemia (CP-CML) or who had documented history of presence of T315I mutation after receiving any number of prior TKIs. Dose reduction at response occurred per study protocol. The trial is expected to inform the optimal use of ICLUSIG (ponatinib) in these patients. 282 patients were enrolled at clinical sites around the world, with 94 patients receiving the 45-mg starting dose. The primary endpoint of the trial is achieving ≤1% BCR-ABL1IS at 12 months.

OPTIC data showed that optimal benefit-risk with ICLUSIG can be obtained with a response-based dosing regimen, 45-mg/day to 15-mg/day upon achieving ≤1% BCR-ABL1IS in patients with CP-CML highly resistant to prior TKI therapies both with or without mutations. At 12 months, 44% (41/93) of patients who received the 45-mg starting dose achieved ≤1% BCR-ABL1IS. At a median follow up time of 32 months, the OPTIC study showed that, among patients receiving ICLUSIG 45- to 15-mg, 73% maintained their response. In these patients, 10% experienced an AOE of any Grade, 5% experienced Grade 3 or higher. The most common TEAEs occurring in > 15% of patients were thrombocytopenia, hypertension, headache, neutropenia, anemia, headache, lipase increased, alanine aminotransferase (ALT) increased, and arthralgia.

About CML and Ph+ ALL

CML – a rare malignancy – is one of four main types of leukemia; it is a result of a genetic mutation that takes place in early, immature versions of myeloid cells, which form red blood cells, platelets and most types of white blood cells. Subsequently, an abnormal gene called BCR-ABL1 forms, turning the damaged cell into a CML cell. CML typically progresses slowly, but it can change into a fast-growing acute leukemia that is hard to treat.

Ph+ ALL is a rare form of ALL that affects approximately 25% of adult ALL patients in the U.S. and is characterized by the presence of an abnormal gene, known as the Philadelphia chromosome. In patients who are Philadelphia chromosome-positive (Ph+), an abnormal chromosome is formed when pieces of chromosomes 9 and 22 switch with each other. This forms a longer chromosome 9 and a shorter chromosome 22, which leads to the development of BCR-ABL1 and is associated with Ph+ ALL.

About ICLUSIG (ponatinib) tablets

ICLUSIG is a kinase inhibitor targeting BCR-ABL1, an abnormal tyrosine kinase that is expressed in CML and Ph+ ALL. ICLUSIG is a targeted cancer medicine developed using a computational and structure-based drug-design platform, specifically designed to inhibit the activity of BCR-ABL1 and its mutations. ICLUSIG inhibits native BCR-ABL1, as well as all BCR-ABL1 treatment-resistant mutations, including the most resistant T315I mutation. ICLUSIG is the only approved TKI that demonstrates activity against the T315I gatekeeper mutation of BCR-ABL1. This mutation has been associated with resistance to all other approved TKIs. ICLUSIG received full approval from the FDA in November 2016. ICLUSIG is indicated for the treatment of adult patients with chronic-phase (CP) CML with resistance or intolerance to at least two prior kinase inhibitors, accelerated-phase (AP) or blast-phase (BP) CML or Ph+ ALL for whom no other kinase inhibitor is indicated, and T315I+ CML (CP, AP or BP) or T315I-positive Ph+ ALL. ICLUSIG is not indicated and is not recommended for the treatment of patients with newly diagnosed CP-CML.

IMPORTANT SAFETY INFORMATION

WARNING: ARTERIAL OCCLUSIVE EVENTS, VENOUS THROMBOEMBOLIC EVENTS, HEART FAILURE, and HEPATOTOXICITY

See full prescribing information for complete boxed warning.

Arterial occlusive events (AOEs), including fatalities, have occurred in ICLUSIG-treated patients. AOEs included fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. Monitor for evidence of AOEs. Interrupt or discontinue ICLUSIG based on severity. Consider benefit-risk to guide a decision to restart ICLUSIG.
Venous thromboembolic events (VTEs) have occurred in ICLUSIG-treated patients. Monitor for evidence of VTEs. Interrupt or discontinue ICLUSIG based on severity.
Heart failure, including fatalities, occurred in ICLUSIG-treated patients. Monitor for heart failure and manage patients as clinically indicated. Interrupt or discontinue ICLUSIG for new or worsening heart failure.
Hepatotoxicity, liver failure and death have occurred in ICLUSIG-treated patients. Monitor liver function tests. Interrupt or discontinue ICLUSIG based on severity.
WARNINGS AND PRECAUTIONS

Arterial Occlusive Events (AOEs): AOEs, including fatalities, have occurred in patients who received ICLUSIG in OPTIC and PACE. These included cardiovascular, cerebrovascular, and peripheral vascular events. The incidence of AOEs in OPTIC (45 mg→15 mg) was 13% of 94 patients; 5% experienced Grade 3 or 4. In PACE, the incidence of AOEs was 26% of 449 patients; 14% experienced Grade 3 or 4. Fatal AOEs occurred in 2.1% of patients in OPTIC, and in 2% of patients in PACE. Some patients in PACE experienced recurrent or multisite vascular occlusion. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events. The most common risk factors observed with these events in PACE were history of hypertension, hypercholesterolemia, and non-ischemic cardiac disease. In OPTIC and PACE, AOEs were more frequent with increasing age.

In OPTIC, patients with uncontrolled hypertension or diabetes and patients with clinically significant, uncontrolled, or active cardiovascular disease were excluded. In PACE, patients with uncontrolled hypertriglyceridemia and patients with clinically significant or active cardiovascular disease within the 3 months prior to the first dose of ICLUSIG were excluded. Consider whether the benefits of ICLUSIG are expected to exceed the risks.

Monitor for evidence of AOEs. Interrupt, then resume at the same or decreased dose or discontinue ICLUSIG based on recurrence/severity. Consider benefit-risk to guide a decision to restart ICLUSIG.

Venous Thromboembolic Events (VTEs): Serious or severe VTEs have occurred in patients who received ICLUSIG. In PACE, VTEs occurred in 6% of 449 patients including serious or severe (Grade 3 or 4) VTEs in 5.8% of patients. VTEs included deep venous thrombosis, pulmonary embolism, superficial thrombophlebitis, retinal vein occlusion, and retinal vein thrombosis with vision loss. The incidence was higher in patients with Ph+ ALL (9% of 32 patients) and BP-CML (10% of 62 patients). One of 94 patients in OPTIC experienced a VTE (Grade 1 retinal vein occlusion). Monitor for evidence of VTEs. Interrupt, then resume at the same or decreased dose or discontinue ICLUSIG based on recurrence/severity.

Heart Failure: Fatal, serious or severe heart failure events have occurred in patients who received ICLUSIG. In PACE, heart failure occurred in 9% of 449 patients; 7% experienced serious or severe (Grade 3 or higher). Heart failure occurred in 12% of 94 patients in OPTIC; 1.1% experienced serious or severe (Grade 3 or 4). In PACE, the most frequently reported heart failure events (≥2%) were congestive cardiac failure (3.1%), decreased ejection fraction (2.9%), and cardiac failure (2%). In OPTIC, the most frequently reported heart failure events (>1 patient each) were left ventricular hypertrophy (2.1%) and BNP increased (2.1%). Monitor patients for signs or symptoms consistent with heart failure and manage heart failure as clinically indicated. Interrupt, then resume at reduced dose or discontinue ICLUSIG for new or worsening heart failure.

Hepatotoxicity: ICLUSIG can cause hepatotoxicity, including liver failure and death. Fulminant hepatic failure leading to death occurred in 3 patients, with hepatic failure occurring within 1 week of starting ICLUSIG in one of these patients. These fatal cases occurred in patients with BP-CML or Ph+ ALL. Hepatotoxicity occurred in 25% of 94 patients in OPTIC and 32% of 449 patients in PACE. Grade 3 or 4 hepatotoxicity occurred in OPTIC (6% of 94 patients) and PACE (13% of 449 patients). The most frequent hepatotoxic events were elevations of ALT, AST, GGT, bilirubin, and alkaline phosphatase. Monitor liver function tests at baseline, then at least monthly or as clinically indicated. Interrupt, then resume at a reduced dose or discontinue ICLUSIG based on recurrence/severity.

Hypertension: Serious or severe hypertension, including hypertensive crisis, has occurred in patients who received ICLUSIG. Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. Monitor blood pressure at baseline and as clinically indicated and manage hypertension as clinically indicated. Interrupt, dose reduce, or stop ICLUSIG if hypertension is not medically controlled. For significant worsening, labile or treatment-resistant hypertension, interrupt ICLUSIG and consider evaluating for renal artery stenosis.

Pancreatitis: Serious or severe pancreatitis has occurred in patients who received ICLUSIG. Elevations of lipase and amylase also occurred. In the majority of cases that led to dose modification or treatment discontinuation, pancreatitis resolved within 2 weeks. Monitor serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on severity. Evaluate for pancreatitis when lipase elevation is accompanied by abdominal symptoms.

Increased Toxicity in Newly Diagnosed Chronic Phase CML: In a prospective randomized clinical trial in the first line treatment of newly diagnosed patients with CP-CML, single agent ICLUSIG 45 mg once daily increased the risk of serious adverse reactions 2-fold compared to single agent imatinib 400 mg once daily. The median exposure to treatment was less than 6 months. The trial was halted for safety. Arterial and venous thrombosis and occlusions occurred at least twice as frequently in the ICLUSIG arm compared to the imatinib arm. Compared to imatinib-treated patients, ICLUSIG-treated patients exhibited a greater incidence of myelosuppression, pancreatitis, hepatotoxicity, cardiac failure, hypertension, and skin and subcutaneous tissue disorders. ICLUSIG is not indicated and is not recommended for the treatment of patients with newly diagnosed CP-CML.

Neuropathy: Peripheral and cranial neuropathy occurred in patients in OPTIC and PACE. Some of these events in PACE were Grade 3 or 4. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Ocular Toxicity: Serious or severe ocular toxicity leading to blindness or blurred vision have occurred in ICLUSIG-treated patients. The most frequent ocular toxicities occurring in OPTIC and PACE were dry eye, blurred vision, and eye pain. Retinal toxicities included age-related macular degeneration, macular edema, retinal vein occlusion, retinal hemorrhage, and vitreous floaters. Conduct comprehensive eye exams at baseline and periodically during treatment.

Hemorrhage: Fatal and serious hemorrhage events have occurred in patients who received ICLUSIG. Fatal hemorrhages occurred in PACE and serious hemorrhages occurred in OPTIC and PACE. The incidence of serious bleeding events was higher in patients with AP-CML, BP-CML, and Ph+ ALL. Gastrointestinal hemorrhage and subdural hematoma were the most frequently reported serious hemorrhages. Events often occurred in patients with Grade 4 thrombocytopenia. Monitor for hemorrhage and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Fluid Retention: Fatal and serious fluid retention events have occurred in patients who received ICLUSIG. In PACE, one instance of brain edema was fatal and serious events included pleural effusion, pericardial effusion, and angioedema. Monitor for fluid retention and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Cardiac Arrhythmias: Cardiac arrhythmias, including ventricular and atrial arrhythmias, occurred in patients in OPTIC and PACE. For some patients, events were serious or severe (Grade 3 or 4) and led to hospitalization. Monitor for signs and symptoms suggestive of slow heart rate (fainting, dizziness) or rapid heart rate (chest pain, palpitations or dizziness) and manage patients as clinically indicated. Interrupt, then resume at the same or reduced dose or discontinue ICLUSIG based on recurrence/severity.

Myelosuppression: Grade 3 or 4 events of neutropenia, thrombocytopenia, and anemia occurred in patients in OPTIC and PACE. The incidence of myelosuppression was greater in patients with AP-CML, BP-CML, and Ph+ ALL than in patients with CP-CML. Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated. If ANC less than 1 x 109/L or platelets less than 50 x 109/L, interrupt ICLUSIG until ANC at least 1.5 x 109/L and platelets at least 75 x 109/L, then resume at same or reduced dose.

Tumor Lysis Syndrome (TLS): Serious TLS was reported in ICLUSIG-treated patients in OPTIC and PACE. Ensure adequate hydration and treat high uric acid levels prior to initiating ICLUSIG.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS (also known as Posterior Reversible Encephalopathy Syndrome) has been reported in patients who received ICLUSIG. Along with neurological signs and symptoms, hypertension may be present. Diagnosis is made with supportive findings on magnetic resonance imaging (MRI) of the brain. Interrupt ICLUSIG until resolution. The safety of resumption of ICLUSIG in patients upon resolution of RPLS is unknown.

Impaired Wound Healing and Gastrointestinal Perforation: Impaired wound healing occurred in patients receiving ICLUSIG. Withhold ICLUSIG for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of ICLUSIG after resolution of wound healing complications has not been established. Gastrointestinal perforation or fistula occurred in patients receiving ICLUSIG. Permanently discontinue in patients with gastrointestinal perforation.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings from animal studies, ICLUSIG can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, adverse developmental effects occurred at exposures lower than human exposures at the recommended human dose. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with ICLUSIG and for 3 weeks after the last dose.

ADVERSE REACTIONS

The most common (>20%) adverse reactions are rash and related conditions, arthralgia, abdominal pain, headache, constipation, dry skin, hypertension, fatigue, fluid retention and edema, pyrexia, nausea, pancreatitis/lipase elevation, hemorrhage, anemia, hepatic dysfunction and AOEs. The most common Grade 3 or 4 laboratory abnormalities (>20%) are platelet count decreased, neutrophil cell count decreased, and white blood cell decreased.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceutical Co. Ltd. At 1-844-817-6468 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid coadministration or reduce ICLUSIG dose if coadministration cannot be avoided.

Strong CYP3A Inducers: Avoid coadministration.

USE IN SPECIFIC POPULATIONS

Females and Males of Reproductive Potential: Verify pregnancy status of females of reproductive potential prior to initiating ICLUSIG.

Ponatinib may impair fertility in females, and it is not known if these effects are reversible.

Lactation: Advise women not to breastfeed during treatment with ICLUSIG and for 6 days following last dose.

For more information about ICLUSIG, visit www.ICLUSIG.com. For the Prescribing Information including the Boxed Warning for arterial occlusion, venous thromboembolism, heart failure, and hepatoxicity, please visit View Source For more information about ongoing research, please visit www.clinicaltrials.gov.

Takeda’s Commitment to Oncology

Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.

On May 19, 2021 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO), a global biotech company focused on the development of therapies for difficult-to-treat hematological diseases, reported that three abstracts with data on melflufen (INN melphalan flufenamide) in relapsed refractory multiple myeloma, RRMM, have been accepted by the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), ASCO (Free ASCO Whitepaper), and have now been published online (Press release, Oncopeptides, MAY 19, 2021, View Source [SID1234580323]). The clinical data presentations include updates on Oncopeptides’ ANCHOR and LIGHTHOUSE studies as well as a pooled analysis of the O-12-M1 and HORIZON studies in patients who have been exposed to or become refractory to prior alkylators.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"The phase 1/2 ANCHOR study of melflufen plus dexamethasone in combination with either daratumumab or bortezomib shows encouraging clinical activity in heavily pre-treated patients with relapsed refractory multiple myeloma, and the optimal dose of melflufen has now been established for both regimens," says Klaas Bakker, MD, PhD, Executive Vice President and Chief Medical Officer, Oncopeptides AB. "We will now complete patient enrolment in the bortezomib arm, while the daratumumab arm is already fully accrued, as presented at the American Hematology Association meeting in December 2020, where updated safety and efficacy data from ANCHOR were presented. The data presented here at ASCO (Free ASCO Whitepaper) data clearly support further development of melflufen in triplet regimens and reinforce the rational for the ongoing phase 3 LIGHTHOUSE study, comparing melflufen plus dexamethasone in combination with subcutaneous daratumumab with daratumumab alone."

Below is a brief description of the abstracts that have been accepted by the ASCO (Free ASCO Whitepaper). They will be available online at View Source, on May 19th at 23:00 (CET).

1. ANCHOR (OP-104): MELFLUFEN PLUS DEXAMETHASONE AND BORTEZOMIB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS
The ANCHOR study determined that the optimal dose of melflufen is 30 mg plus dexamethasone and bortezomib and the results showed clinical activity in heavily pretreated RRMM patients. Recruitment for this study is ongoing and updated data including efficacy and safety will be presented at ASCO (Free ASCO Whitepaper).

2. LIGHTHOUSE (OP-108): A PHASE 3 STUDY OF MELFLUFEN IN COMBINATION WITH DEXAMETHASONE AND DARATUMUMAB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS
The phase 3 LIGHTHOUSE study is a randomized, controlled, open-label study of melflufen plus dexamethasone in combination with daratumumab vs daratumumab alone in patients with RRMM previously treated with an immunomodulatory agent and a proteasome inhibitor, similar to the indication for daratumumab monotherapy. The primary objective is superiority of PFS. Key secondary endpoints include ORR (≥ PR), DOR, and safety. Patient recruitment is ongoing with a planned enrolment of 240 patients.

3. A POOLED ANALYSIS OF THE O-12-M1 AND HORIZON STUDIES: MELFLUFEN PLUS DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS (RRMM) WHO ARE EXPOSED OR REFRACTORY TO PRIOR ALKYLATORS
This pooled analysis of the O-12-M1 and HORIZON studies showed that melflufen in combination with dexamethasone showed meaningful efficacy and demonstrated a clinically manageable safety profile in patients with RRMM who had been exposed or become refractory to prior alkylators.

PEPAXTO (melphalan flufenamide, also known as melflufen), in combination with dexamethasone, was granted accelerated approval by the FDA on February 26, 2021, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.

For more information, please contact:

Rolf Gulliksen, Global Head of Corporate Communications, Oncopeptides AB (publ)
E-mail: [email protected]
Cell phone: + 46 70 262 96 28

Linda Holmström, Director of Investor Relations, Oncopeptides AB (publ)
E-mail: [email protected]
Cell phone: +46 70 873 40 95

About melphalan flufenamide

Melphalan flufenamide, also known as melflufen, is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly releases alkylating agents inside cancer cells. Aminopeptidases are overexpressed in multiple myeloma cells and are associated with advanced disease and tumor mutational burden. Targeting aminopeptidases causes selective activity in cancer cells, sparing healthy cells.

In the US, PEPAXTO (melphalan flufenamide) is indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.