On November 6, 2019 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that seven abstracts covering data from the company’s research and clinical portfolio have been accepted for presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, to be held December 7-10, 2019 in Orlando (Press release, GlycoMimetics, NOV 6, 2019, View Source [SID1234550539]).

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Of particular note, clinical data from the Company’s recent Phase 1/2 study of uproleselan, an E-selectin antagonist and the company’s lead wholly owned clinical candidate, were selected for a poster presentation on Sunday, December 8 during a session on biology of AML. The presentation will feature data showing uproleselan’s ability to reverse chemoresistance in patients who have high-risk clinical features and over-express the E-selectin ligand. The poster presentation will highlight the potential benefits of this novel candidate, which resulted in an overall survival of 12.7 months in a high-risk group of patients when added to salvage chemotherapy – longer than expected survival based on clinical variables alone.

A poster presentation of complementary work by investigators at the Fred Hutchinson Cancer Research Center will highlight research identifying the unique gene expression signature that is a surrogate for E-selectin ligand expression on leukemic cells. For the first time, in a large clinical database, independent analysis of glycogene signature demonstrated that E-selectin ligand expression is associated with poor survival in pediatric patients with AML.

"The collective data from this year’s posters and presentations support the fact that E-selectin plays a major role in chemoresistance in AML, and we are excited to share results showing that uproleselan can counter resistance by augmenting deep clinical responses – and ultimately may prolong survival," said GlycoMimetics Senior Vice President of Clinical Development and Chief Medical Officer Helen Thackray, M.D., FAAP. "As a pioneer in the field of environment-mediated drug resistance in oncology, the GlycoMimetics team is applying its proprietary technology to discover and develop drugs that target these pathways. In addition, we are actively studying key related biomarkers in multiple cancers and exploring additional ways to incorporate these recent discoveries into our development program."

Other GlycoMimetics presentations will showcase research on how the E-selectin binding potential of AML blasts is altered during therapy and how these variations influence treatment outcomes, as well as investigations into which AML cell surface receptors mediate E-selectin induced chemo-resistance.

Presentation Details:

Publication Number: 2690
TITLE: High E-Selectin Ligand Expression Contributes to Chemotherapy-Resistance in Poor Risk Relapsed and Refractory (R/R) Acute Myeloid Leukemia (AML) Patients and Can be Overcome with the Addition of Uproleselan
Session Name: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster II
Session Date: Sunday, December 8, 2019
Presentation Time: 6:00 PM – 8:00 PM EST
Location: Orange County Convention Center, Hall B

Publication Number: 2650
TITLE: A Double-Blind, Placebo-Controlled, Phase 3 Registration Trial to Evaluate the Efficacy of Uproleselan (GMI-1271) with Standard Salvage Chemotherapy in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia
Session Name: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II
Session Date: Sunday, December 8, 2019
Presentation Time: 6:00 PM – 8:00 PM EST
Location: Orange County Convention Center, Hall B

Publication Number: 1366
TITLE: A Randomized Phase 2/3 Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults with Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy
Session Name: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I
Session Date: Saturday, December 7, 2019
Presentation Time: 5:30 PM – 7:30 PM EST
Location: Orange County Convention Center, Hall B

Publication Number: 3802
TITLE: Synergistic Targeting of BTK and E-Selectin/CXCR4 in the Microenvironment of Mantle Cell Lymphomas
Session Name: 605. Molecular Pharmacology, Drug Resistance—Lymphoid and Other Diseases: Poster III
Session Date: Monday, December 9, 2019
Presentation Time: 6:00 PM – 8:00 PM EST
Location: Orange County Convention Center, Hall B

Publication Number: 907
TITLE: CD162 Is a Key E-Selectin Receptor Promoting Acute Myeloid Leukemia Chemo-Resistance in the Bone Marrow Niche
Session Name: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: The Impact of Cell-Cell Interactions, Surface Antigens, and Mitochondria
Session Date: Monday, December 9, 2019
Session Time: 6:15 PM – 7:45 PM EST
Presentation Time: 6:15 PM EST
Room: Orange County Convention Center, W308

Publication Number: 2657
TITLE: Blocking Vascular Niche E-Selectin Dampens AML Stem Cell Regeneration/Survival Potential In Vivo By Inhibiting MAPK/ERK and PI3K/AKT Signaling Pathways
Session Name: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II
Session Date: Sunday, December 8, 2019
Presentation Time: 6:00 PM – 8:00 PM EST
Location: Orange County Convention Center, Hall B

Publication Number: 3772
TITLE: Transcriptome Profiling of Glycosylation Genes Defines Correlation with E-selectin Ligand Expression and Clinical Outcome
Session Name: 602. Disordered Gene Expression in Hematologic Malignancy, including Disordered Epigenetic Regulation: Poster III
Session Date: Monday, December 9, 2019
Presentation Time: 6:00 PM – 8:00 PM
Location: Orange County Convention Center, Hall B

Meeting abstracts are available on ASH (Free ASH Whitepaper)’s website.

About Uproleselan (GMI-1271)

Uproleselan (yoo’ pro le’ sel an), currently in a comprehensive Phase 3 development program in AML, has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of adult AML patients with relapsed or refractory disease. Uproleselan is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. In a Phase 1/2 clinical trial, uproleselan was evaluated in both newly diagnosed elderly and relapsed or refractory patients with AML. In both populations, patients treated with uproleselan together with standard chemotherapy achieved better-than-expected remission rates and overall survival compared to historical controls, which have been derived from results from third-party clinical trials evaluating standard chemotherapy, as well as lower-than-expected induction-related mortality rates. Treatment in these patient populations was generally well tolerated, with fewer than expected adverse effects.

On November 6, 2019 FORMA Therapeutics, Inc., a clinical stage biopharmaceutical company focused on rare hematological diseases and cancers, reported that three abstracts have been accepted for presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in Orlando, Florida from December 7-10, 2019 (Press release, Forma Therapeutics, NOV 6, 2019, View Source [SID1234550538]).

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Three oral presentations on lead assets will feature data: olutasidenib, a next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1m) in development for the treatment of patients with relapsed/refractory acute myeloid leukemia (RR/AML) or myelodysplastic syndrome (MDS), and patients with glioma and other solid tumors with an IDH1 mutation; and FT-4202, a novel selective red blood cell (RBC) pyruvate kinase (PKR) activator in development as a potentially disease-modifying therapy for the treatment of sickle cell disease (SCD). A poster presentation will feature data for a FORMA-discovered asset licensed to Celgene Corporation, FT-1101, an oral, structurally distinct and potent pan-inhibitor of the Bromodomain and Extra-Terminal (BET) epigenetic protein family.

The accepted abstracts are available online through the ASH (Free ASH Whitepaper) conference website, View Source, and include:

Oral Presentations

Title: Olutasidenib (FT-2102), an IDH1m Inhibitor As a Single Agent or in Combination with Azacitidine, Induces Deep Clinical Responses with Mutation Clearance in Patients with Acute Myeloid Leukemia Treated in a Phase 1 Dose Escalation and Expansion Study

Date/Time: Saturday, December 7, 2019 at 2:30 p.m. ET
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel Targets and Combinations
Abstract: 231
Location: Orange County Convention Center, Chapin Theater (W320)
Presenter: Justin Watts, MD. Assistant Professor University of Miami, Sylvester Comprehensive Cancer Center

Title: Olutasidenib (FT-2102), Induces Rapid Remissions in Patients with IDH1-Mutant Myelodysplastic Syndrome: Results of Phase 1/2 Single Agent Treatment and Combination with Azacitidine

Date/Time: Monday, December 9, 2019 at 10:45 a.m. ET
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Targeting Gene Mutations in MDS
Abstract: 674
Location: Orange County Convention Center, W311ABCD
Presenter: Jorge E. Cortes, MD. Professor, Augusta University, Director of the Georgia Cancer Center

Title: Phase 1 Single (SAD) and Multiple Ascending Dose (MAD) Studies of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of FT-4202, an Allosteric Activator of Pyruvate Kinase-R, in Healthy and Sickle Cell Disease Subjects

The presentation will report the effects of FT-4202 on healthy subjects in this ongoing study.

Date/Time: Monday, December 9, 2019 at 11:15 a.m. ET
Session: 114. Hemoglobinopathies, Excluding Thalassemia—Clinical: Emerging Therapies: Reports from Recent Clinical Trials
Abstract: 616
Location: Orange County Convention Center, W304ABCD
Presenter: Theodosia Kalfa, MD, PhD. Associate Professor, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center

Poster Presentation

Title: Phase 1 Dose Escalation and Expansion Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the BET Inhibitor FT-1101 As a Single Agent in Patients with Relapsed or Refractory Hematologic Malignancies

Date/Time: Monday, December 9, 2019 from 6:00 – 8:00 p.m. ET
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
Abstract: 3907
Location: Orange County Convention Center, Hall B
Presenter: Manish Patel, MD. Director of Drug Development, Florida Cancer Specialists. Associate Director of Drug Development, Sarah Cannon Research Institute

About Olutasidenib (FT-2102)

FORMA’s most advanced clinical asset, olutasidenib, is a potent and selective next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1) being investigated to treat patients with relapsed/refractory acute myeloid leukemia (RR/AML) or myelodysplastic syndrome (MDS), and patients with glioma and other solid tumors with an IDH1 mutation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. Mutations of IDH1 can produce excessive amounts of the oncometabolite 2-hydroxyglutarate (2-HG), which impairs cell differentiation and promotes blood malignancies and solid tumors. IDH1 mutations are present in 7-14% of patients with AML and 3-4% of patients with MDS.

About FT-4202

FT-4202 is a novel selective red blood cell (RBC) pyruvate kinase (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD), with a multimodal approach. FT-4202 works upstream by activating the RBCs’ natural PKR activity to decrease 2,3-DPG levels, which leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. The downstream activity of FT-4202 increases ATP levels, the fuel that provides energy to cells, to improve RBC health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. SCD is the most common disorder caused by a single gene mutation and affects approximately 100,000 people in the U.S., and millions globally.

About FT-1101 (also known as CC-95775)

FT-1101 (also known as CC-95775) is an oral, structurally distinct and potent pan-inhibitor of the Bromodomain and Extra-Terminal (BET) epigenetic protein family, which was discovered by FORMA and licensed to Celgene Corporation.

On November 6, 2019 Biopharmaceutical company Alvotech and global pharmaceutical company STADA Arzneimittel AG ("STADA") reported that they have entered into an exclusive strategic partnership for the commercialization of seven biosimilars in all key European markets and selected markets outside Europe (Press release, Alvotech, NOV 6, 2019, View Source [SID1234550537]). The initial pipeline contains biosimilar candidates aimed at treating autoimmunity, oncology and inflammatory conditions as well as ophthalmology for patients around the world.

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Under this partnership agreement, Alvotech will be responsible for the development, registration and supply of the biosimilars within the EU. STADA will be exclusively commercializing the products in the majority of the key European markets. The originator products of the seven biosimilars currently generate $50 billion in sales globally, allowing the two parties to agree on a particularly lucrative contract. The agreement includes an upfront payment with subsequent milestone payments over the next four years.

Robert Wessman, Alvotech’s founder and Chairman, added, "This is an important moment for biosimilars. This partnership has the resources and vision to accelerate the introduction and adoption of new biosimilars for patients in Europe who will get better access to high-quality products. It’s also another important milestone for Alvotech and crowns an exceptional year where we have continued to extend our network of partners around the globe."

"We’re delighted to establish this latest partnership with STADA, who is an ideal commercial partner in Europe and shares the same purpose of improving the quality of life of patients around the world," added Mark Levick, CEO of Alvotech.

Peter Goldschmidt, Chairman of the Executive Board/CEO of STADA, said, "The collaboration with Alvotech, with its highly experienced and fully committed team, is a great opportunity to accelerate the expansion of our biosimilar portfolio and to strengthen our market position in this segment. We are looking forward to provide patients with state-of-the-art medicine and cost-effective alternatives to biologicals."

On November 6, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical-stage biopharmaceutical company pioneering a novel class of immunotherapies, reported that updated results from SPiRel, a Phase 2 study of the Company’s lead program, DPX-Survivac, as a combination therapy in patients with recurrent/refractory diffuse large B-cell lymphoma (DLBCL), will be featured in a poster session at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, being held December 7-10, 2019 in Orlando, FL (Press release, IMV, NOV 6, 2019, View Source [SID1234550536]).

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Poster Presentation Details:

Poster Title: Combination of DPX-Survivac, Low Dose Cyclophosphamide, and Pembrolizumab in Recurrent/Refractory DLBCL: The SPiReL Study

Presenter: Neil Berinstein, MD, FRCPC, ABIM, Haematologist at the Sunnybrook Health Sciences Centre, Toronto, ON.

Publication Number: 3236

Session Name: 704. Immunotherapies: poster II

Date and Time: December 8, 2019, 6:00 p.m. – 8:00 p.m. EDT

Location: Orange County Convention Center, Hall B

The American Society of Hematology (ASH) (Free ASH Whitepaper) has published the official abstracts on its meeting website in advance of the ASH (Free ASH Whitepaper) Annual Meeting.

The final conference poster presentation will include additional data collected between the abstract submission on June 27, 2019 and the presentation itself. The poster will be available under Events, Webcasts and Presentations in the investors section of IMV’s website on the day of presentation.

About the SPiReL study

"SPiReL" is a Phase 2 non-randomized, open label, efficacy and safety study. Eligible subjects have recurrent/refractory DLBCL, confirmed expression of survivin are eligible for curative therapy. Study treatment includes administering two doses of 0.5 mL of DPX-Survivac 3 weeks apart followed by up to six 0.1 mL doses every 8 weeks. Intermittent low dose cyclophosphamide is administered orally at 50 mg twice daily for 7 days followed by 7 days off. Pembrolizumab 200 mg is administered every 3 weeks. Study participants continue active therapy for up to one year or until disease progression, whichever occurs first.

The primary objective of this study is to document the response rate to this treatment combination using modified Cheson criteria. Secondary objectives include duration of response and safety. Exploratory endpoints include T cell response, tumor immune cell infiltration, and gene expression analysis. Enrollment is ongoing with a goal of up to 25 subjects in this multi-center study.

At the time of data cut-off for the abstract on June 27, 2019, 23 subjects have been screened and 12 have been enrolled.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapies that programs targeted T cells in vivo. It has demonstrated the potential for industry-leading targeted, persistent, and durable CD8+ T cell generation. IMV believes this mechanism of action (MOA) is key to generating durable solid tumor regressions. DPX-Survivac consists of survivin-based peptides formulated in IMV’s proprietary DPX drug delivery platform. DPX-Survivac is designed to work by eliciting a cytotoxic T cell immune response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to chemotherapies. IMV has identified over 20 cancer indications in which survivin can be targeted by DPX-Survivac.

DPX-Survivac has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as orphan drug designation status from the U.S. FDA and the European Medicines Agency (EMA) in the ovarian cancer indication.

On November 6, 2019 Kite, a Gilead Company (Nasdaq: GILD), reported the acceptance of eight abstracts, including five oral presentations, for Yescarta (axicabtagene ciloleucel) and other ongoing research from the company’s chimeric antigen receptor (CAR) T cell therapy development program, at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, in Orlando from December 7–10, 2019 (Press release, Kite Pharma, NOV 6, 2019, View Source [SID1234550535]).

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Data from Kite’s CAR T cell therapy development program to be presented at the meeting include survival data at three years from the pivotal ZUMA-1 trial of Yescarta in patients with refractory large B-cell lymphoma to be highlighted in the ZUMA-1 mechanism of relapse presentation below (Abstract #203), as well as primary results from a cohort investigating the effect of earlier steroid use with Yescarta on the rates of cytokine release syndrome and neurologic events (Abstract #243). Real-world data on Yescarta, including an analysis of post-marketing outcomes for Yescarta in large B-cell lymphoma (Abstract #764), as well as the primary analysis for the ZUMA-2 study evaluating investigational KTE-X19 in relapsed or refractory mantle cell lymphoma (Abstract #754), will also be presented.

"As we continue to lead the field in cell therapy, this year’s ASH (Free ASH Whitepaper) Annual Meeting will be a seminal one for Kite," said Christi Shaw, Chief Executive Officer of Kite. "We are excited to share three-year survival data, insights into potential adverse event management and findings from other studies that help further the understanding of Yescarta and cell therapy as we aim to bring this potentially life-saving treatment approach to as many appropriate people with blood cancers as possible."

Yescarta was the first CAR T cell therapy to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, and high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of cytokine release syndrome and neurologic toxicities; see below for Important Safety Information.

Dates and times for presentations are as follows:

Area of Focus, Presentation Number and Date/Time (ET)

Abstract Title

Presentations

Large B-cell Lymphoma
Abstract #203 (Oral)
Saturday, Dec 7 (1:00 pm)

CD19-Loss with Preservation of Other B-Cell Lineage Features with Large B-Cell Lymphoma Who Relapsed Post-Axi-Cel

Large B-cell Lymphoma
Abstract #243 (Oral)
Saturday, Dec 7 (2:30 pm)

Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B-Cell Lymphoma

Large B-cell Lymphoma
Abstract #793 (Oral)
Monday, Dec 9 (2:45 pm)

Medicare Patients Receiving Chimeric Antigen Receptor T Cell Therapy for Non-Hodgkin Lymphoma: A First Real-world Look at Patient Characteristics, Healthcare Utilization and Costs

Large B-cell Lymphoma
Abstract #764 (Oral)
Monday, Dec 9 (3:00 pm)

Outcomes of Post-marketing Use of an Anti-CD19 CAR T Cell Therapy, Axicabtagene Ciloleucel (Axi-Cel), for the Treatment of Large B-Cell Lymphoma in the United States

Mantle Cell Lymphoma
Abstract #754 (Oral)
Monday, Dec 9 (3:30 pm)

KTE-X19, an Anti-CD19 CAR T Cell Therapy, in Patients with Relapsed/Refractory Mantle Cell Lymphoma: Results of the Phase 2 ZUMA-2 Study

Large B-cell Lymphoma
Abstract #4095 (Poster)
Monday, Dec 9 (6:00-8:00 pm)

A Comparison of Two-year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel) and SCHOLAR-1 in Patients with Refractory Large B-Cell Lymphoma

Trials-In-Progress

Large B-cell Lymphoma
Abstract #4084 (Poster)
Monday, Dec 9 (6:00-8:00 pm)

ZUMA-11: A Phase 1/2 Multicenter Study of Axicabtagene Ciloleucel (Axi-Cel) + Utomilumab in Patients with Refractory Large B-Cell Lymphoma

Large B-cell Lymphoma
Abstract #4093 (Poster)
Monday, Dec 9 (6:00-8:00 pm)

A Phase 2, Open-label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination with Either Rituximab or Lenalidomide in Patients with Refractory Large B-Cell Lymphoma (ZUMA-14)

For more information, including a complete list of abstract titles at the meeting, please visit: View Source

The use of Yescarta with utomilumab, rituximab, or lenalidomide is investigational and not approved globally. Efficacy and safety of these potential combinations have not been established. KTE-X19 is investigational and not approved anywhere globally. Its efficacy and safety have not been established. More information about clinical trials with KTE-X19 is available at www.clinicaltrials.gov.

About KTE-X19

KTE-X19 is an investigational, autologous, anti-CD19 CAR T cell therapy. KTE-X19 uses the XLP manufacturing process that includes T-cell selection and lymphocyte enrichment. Lymphocyte enrichment is a necessary step in certain B-cell malignancies with evidence of circulating lymphoblasts. KTE-X19 is currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL), mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS.
CYTOKINE RELEASE SYNDROME (CRS): CRS occurred in 94% of patients, including 13% with ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to infusion of Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES: Neurologic toxicities occurred in 87% of patients. Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks, with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade 3 or higher occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with Yescarta. Fatal and serious cases of cerebral edema have occurred in patients treated with Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly.

YESCARTA REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS. The required components of the Yescarta REMS are: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YESCARTAREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions may occur. Serious hypersensitivity reactions including anaphylaxis may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients, and in 23% with ≥ Grade 3. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Yescarta infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade 3 or higher cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after Yescarta infusion.

HYPOGAMMAGLOBULINEMIA: B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.