On November 30, 2023 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the Company and its partners will present two abstracts at the 2023 San Antonio Breast Cancer Symposium (SABCS) from December 5-9; 11 abstracts at the 65th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from December 9-12; and two abstracts at the International Association for the Study of Lung Cancer (IASLC) 2023 North America Conference on Lung Cancer (NACLC) from December 1-3 (Press release, Jazz Pharmaceuticals, NOV 30, 2023, View Source [SID1234638077]). New data include updated findings from a Phase 2a trial of the investigational HER2-targeted bispecific antibody zanidatamab in combination with palbociclib and fulvestrant as a chemotherapy-free option for HER2+/ HR+ metastatic breast cancer (mBC).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
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
Schedule Your 30 min Free Demo!
"Following recent trial results showing the potential of zanidatamab to treat HER2-expressing gastric and biliary tract cancers at ASCO (Free ASCO Whitepaper) GI, ASCO (Free ASCO Whitepaper) and ESMO (Free ESMO Whitepaper) this year, we’re excited to share updated data at SABCS in HER2-amplified and hormone receptor-positive metastatic breast cancer when zanidatamab is used in combination to target the HER2, CDK4/6 and hormone receptor pathways," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "SABCS will also feature data from a trial of zanidatamab in neoadjuvant breast cancer. Additionally, we look forward to sharing new data through numerous presentations at ASH (Free ASH Whitepaper) 2023 that underscore our commitment to improving standards of care in blood cancer and other hematologic diseases, as well as real-world findings at NACLC that provide evidence of Zepzelca’s safety in clinical practice for the treatment of second-line small cell lung cancer."
Notable presentations at this year’s SABCS, ASH (Free ASH Whitepaper) and NACLC meetings include:
A SABCS oral presentation (late-breaking abstract) featuring primary results from a Phase 2a study for a chemotherapy-free option in heavily pretreated patients with HER2+/HR+ mBC treated with the combination of zanidatamab plus palbociclib and fulvestrant.
An investigator-sponsored (MD Anderson Cancer Center) SABCS poster presentation featuring results of a Phase 1 trial evaluating neoadjuvant zanidatamab in patients with stage 1 node-negative HER2+ breast cancer as a single-agent chemotherapy-free option.
An ASH (Free ASH Whitepaper) poster presentation of the complete pivotal, Phase 2/3 trial results of Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) in acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL), which includes efficacy, safety and population pharmacokinetic modeling from intramuscular (IM) and intravenous (IV) dosing. The combination of observed and modeled results demonstrates Rylaze achieved therapeutic nadir serum asparaginase activity (NSAA) levels in the vast majority of patients via multiple dosing schedules with a safety profile consistent with prior studies and no new safety signals identified. Treatment‐related adverse events (TRAEs) ≥ grade 3 occurred in 126/228 (55%) patients with no TRAEs that led to death.1
Two NACLC poster presentations of real-world data for Zepzelca (lurbinectedin) in the second-line and later settings for the treatment of small cell lung cancer (SCLC).
The Jazz and partner-supported presentations at SABCS 2023 are:
Zanidatamab Presentations
Presentation Title
Author
Presentation Details (All times CDT)
Primary Results From a Phase 2a Study of Zanidatamab (zani) + Palbociclib (palbo) + Fulvestrant (fulv) in HER2+/HR+ Metastatic Breast Cancer (mBC)
Santiago Escrivá-de-Romani, et al.
Type: Oral
Session: Late Breaking Abstracts
Presentation Number: LBO1-04
Date/Time: Friday, December 8, 2023, 12:20 PM – 12:25 PM
Neoadjuvant Zanidatamab for Stage 1 Node Negative HER2 Positive Breast Cancer (BC)
[IST]
V. Valero, et al.
Type: Poster
Session: Spotlight poster session
Presentation Number: PS09-03
Date / Time: Wednesday, December 6, 2023, 5:30 PM – 6:30 PM
The Jazz-supported presentations at the 2023 ASH (Free ASH Whitepaper) Annual Meeting are:
Rylaze Presentations
Presentation Title
Author
Presentation Details (All times PDT)
Efficacy and Safety of Recombinant Erwinia Asparaginase in Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL): Complete Follow-up of the Children’s Oncology Group (COG) AALL1931 study
Luke Maese, et al.
Type: Poster
Number: 1498
Session: 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster I
Date/Time: Saturday, December 9, 5:30-7:30 PM
Abstract Link
A Meta-analysis Comparing the Relative Efficacy of Pediatric-Inspired Regimens Versus Hyper-CVAD for the Treatment of Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma in Adolescents, Young Adults and Adults
Wenqing Su, et al.
Type: Poster
Number: 3779
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster II
Date/Time: Sunday, December 10, 6:00-8:00 PM
Abstract Link
Asparaginase Collaboration Studies
Presentation Title
Author
Presentation Details
Overcoming Venetoclax (Ven) Resistance Through Glutamine (Gln) Depletion: Final Analysis of the Phase 1 Trial of Ven and Pegcrisantaspase (PegC) Combination in Relapsed and Refractory (R/R) Acute Myeloid Leukemia (AML)
Yuchen Liu, et al.
Type: Oral
Number: 60
Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Upcoming Therapies in Newly Diagnosed and Relapsed/Refractory AML
Date/Time: Saturday, December 9, 10:45 AM
Abstract link
Vyxeos Presentations
Presentation Title
Author
Presentation Details
Population Pharmacokinetic-Pharmacodynamic Modeling of Neutrophil and Platelet Count for Lower-Intensity Therapy of CPX-351 Combined With Venetoclax in Acute Myeloid Leukemia
Yali Liang, et al.
Type: Poster
Number: 2902
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Date/Time: Sunday, December 10, 6:00-8:00 PM
Abstract Link
CPX-351 With Venetoclax in Patients with Relapsed/Refractory Acute Myeloid Leukemia: Results of a Phase Ib Study
Alex Bataller, et al.
Type: Poster
Number: 4259
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Date/Time: Monday, December 11, 6:00-8:00 PM
Abstract link
Phase 2 Study of CPX-351 in Combination with Venetoclax in Patients with Newly Diagnosed, High Risk Acute Myeloid Leukemia
Wei-Ying Jen, et al.
Type: Poster
Number: 4273
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Date/Time: Monday, December 11, 6:00-8:00 PM
Abstract link
Results of a Phase 1/2 Study of Lower Dose CPX-351 for Patients with Int-2 or High Risk IPSS Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia after Failure to Hypomethylating Agents
Guillermo Montalban-Bravo, et al.
Type: Poster
Number: 1873
Session: 637. Myelodysplastic Syndromes Clinical and Epidemiological: Poster I
Date/Time: Saturday, Dec. 9, 5:30 PM-7:30 PM
Abstract link
CRISPR/Cas9 Screen Identifies CPX-351 and 7+3 Regimens Response Modulators with Distinct Sensitive and Resistant Profiles
[IST]
Nam Nguyen, et al.
Type: Poster
Number: 1412
Session: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster I
Date/Time: Saturday, Dec. 9, 5:30-7:30 PM
Abstract link
CPX-351 in Patients with Newly Diagnosed Post Myeloproliferative Neoplasms Acute Myeloid Leukemia
[IST]
Sylvain Garciaz, et al.
Type: Poster
Number: 2917
Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Date/Time: Sunday, Dec. 10, 6:00-8:00 PM
Abstract link
Defitelio Presentations
Presentation Title
Author
Presentation Details
Resolution of Veno-occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) With Defibrotide Following HCT in Adult and Pediatric Patients: Pooled Analysis of DEFIFrance and EBMT PASS Registries
Mohamad Mohty, et al.
Type: Poster
Number: 3527
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Date/Time: Sunday, December 10, 6:00-8:00 PM
Abstract link
A Phase II Study to Evaluate the Safety and Efficacy of Defibrotide and Changes in Plasma Biomarkers in Sickle Cell Disease-Related Acute Chest Syndrome (IND 127812)
[IST]
Edo Schaefer, et al.
Type: Poster
Number: 2520
Session: 114. Sickle cell Disease, Sickle Cell Trait and Other Hemoglobinopathies, Excluding Thalassemias: Clinical and Epidemiological: Poster II
Date/Time: Sunday, December 10, 6:00-8:00 PM
Abstract link
The Jazz-supported presentations at NACLC 2023 are:
Zepzelca Presentations
Presentation Title
Author
Presentation Details (All times CDT)
Real-World Use of Lurbinectedin in Patients with Small Cell Lung Cancer: Jazz EMERGE 402 Updated Analysis
Balazs Halmos, et al.
Type: Poster
Number: PP01.119
Session: Poster Viewing Reception
Date/Time: Saturday, December 2, 5:40-6:55 PM CT
Real-World Effectiveness and Safety Profile of Lurbinectedin and Other Second-Line Treatments in Small Cell Lung Cancer
Apar Ganti, et al.
Type: Poster
Number: PP01.117
Session: Poster Viewing Reception
Date/Time: Saturday, December 2, 2023/5:40-6:55 PM CT
About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.
The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.
About RYLAZE (asparaginase erwinia chrysanthemi (recombinant)-rywn)
RYLAZE, also known as JZP458, is approved in the U.S. for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients one month or older who have developed hypersensitivity to E. coli-derived asparaginase. RYLAZE has orphan drug designation for the treatment of ALL/LBL in the United States. RYLAZE, or recombinant Erwinia is a short-acting distinct asparaginase derived from a novel Pseudomonas fluorescens expression platform to help ensure robustness of supply to meet patient needs. JZP458 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in October 2019 for the treatment of this patient population. RYLAZE was approved as part of the Real-Time Oncology Review program, an initiative of the FDA’s Oncology Center of Excellence designed for efficient delivery of safe and effective cancer treatments to patients.2
The full U.S. Prescribing Information for RYLAZE is available at:
View Source
Important Safety Information for Rylaze
RYLAZE should not be given to people who have had:
Serious allergic reactions to RYLAZE
Serious swelling of the pancreas (stomach pain), serious blood clots, or serious bleeding during previous asparaginase treatment
RYLAZE may cause serious side effects, including:
Allergic reactions (a feeling of tightness in your throat, unusual swelling/redness in your throat and/or tongue, or trouble breathing), some of which may be life-threatening
Swelling of the pancreas (stomach pain), which, if left untreated, may be fatal
Blood clots (may be experienced as headache, arm or leg swelling, shortness of breath, or chest pain), which may be life-threatening
Bleeding, which may be life-threatening
Liver problems
Contact your doctor immediately if any of these side effects occur.
Some of the most common side effects with RYLAZE include: liver problems, nausea and vomiting, bone and muscle pain, infection, tiredness, headache, fever with low white blood cell count, fever, bleeding, mouth swelling (sometimes with sores), pain in the abdomen, decreased appetite, allergic reactions, high blood sugar levels, diarrhea, swelling of the pancreas, and low levels of potassium in your blood.
RYLAZE can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Females of reproductive potential should use effective contraception (other than hormonal contraceptives) during treatment and for 3 months following the final dose. Do not breastfeed while receiving RYLAZE and for 1 week after the final dose.
Tell your healthcare provider if there are any side effects that are bothersome or that do not go away.
These are not all the possible side effects of RYLAZE. For more information, ask your healthcare provider.
Call your doctor for medical advice about any side effects.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088).
About Vyxeos (daunorubicin and cytarabine) liposome for injection
Vyxeos is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor.
In the U.S., Vyxeos (daunorubicin and cytarabine) liposome for injection is indicated for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.3
More information about Vyxeos in the United States, including Full Prescribing Information and BOXED Warning, is available here.
Important Safety Information for VYXEOS
WARNING: VYXEOS has different dosage recommendations from other medications that contain daunorubicin and/or cytarabine. Do not substitute VYXEOS for other daunorubicin and/or cytarabine-containing products.
VYXEOS should not be given to patients who have a history of serious allergic reaction to daunorubicin, cytarabine, or any of its ingredients.
VYXEOS can cause a severe decrease in blood cells (red and white blood cells and cells that prevent bleeding, called platelets) which can result in serious infection or bleeding and possibly lead to death. Your doctor will monitor your blood counts during treatment with VYXEOS. Patients should tell the doctor about new onset fever or symptoms of infection or if they notice signs of bruising or bleeding.
VYXEOS can cause heart-related side effects. Tell your doctor about any history of heart disease, radiation to the chest, or previous chemotherapy. Inform your doctor if you develop symptoms of heart failure such as:
shortness of breath or trouble breathing
swelling or fluid retention, especially in the feet, ankles, or legs
unusual tiredness
VYXEOS may cause allergic reactions including anaphylaxis. Seek immediate medical attention if you develop signs and symptoms of anaphylaxis such as:
trouble breathing
severe itching
skin rash or hives
swelling of the face, lips, mouth, or tongue
VYXEOS contains copper and may cause copper overload in patients with Wilson’s disease or other copper-processing disorders.
VYXEOS can damage the skin if it leaks out of the vein. Tell your doctor right away if you experience symptoms of burning, stinging, or blisters and skin sores at the injection site.
VYXEOS can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Do not breastfeed while receiving VYXEOS. Females and males of reproductive potential should use effective contraception during treatment and for 6 months following the last dose of VYXEOS.
The most common side effects are bleeding events, fever, rash, swelling, nausea, sores in the mouth or throat, diarrhea, constipation, muscle pain, tiredness, stomach pain, difficulty breathing, headache, cough, decreased appetite, irregular heartbeat, pneumonia, blood infection, chills, sleep disorders, and vomiting.
Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Jazz Pharmaceuticals at 1-800-520-5568.
About Defitelio (defibrotide sodium)
In the U.S., Defitelio (defibrotide sodium) injection 80mg/mL received U.S. Food and Drug Administration (FDA) marketing approval on March 30, 2016, and it is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT) and is the first and only FDA-approved therapy for patients with this rare, potentially fatal complication. Defitelio is not approved for the prevention of VOD.6
Please see full Prescribing Information for Defitelio in the United States.
In Europe, defibrotide is marketed under the name Defitelio ▼ (defibrotide). In October 2013, the European Commission granted marketing authorization to Defitelio under exceptional circumstances for the treatment of severe VOD in patients after HSCT therapy. In Europe, Defitelio is indicated in patients over one month of age. It is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy.
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system found under section 4.8 of the SmPC
(View Source)
The full Summary of Product Characteristics of Defitelio in Europe is available here.
Important Safety Information for Defitelio
Defitelio should not be given to patients who are:
Currently taking anticoagulants or fibrinolytics
Allergic to Defitelio or any of its ingredients
Defitelio may increase the risk of bleeding in patients with VOD and should not be given to patients with active bleeding. During treatment with Defitelio, patients should be monitored for signs of bleeding. In the event that bleeding occurs during treatment with Defitelio, treatment should be temporarily or permanently stopped.
Patients should tell the doctor right away about any signs or symptoms of hemorrhage such as unusual bleeding, easy bruising, blood in urine or stool, headache, confusion, slurred speech, or altered vision.
Defitelio may cause allergic reactions including anaphylaxis. Patients who develop signs and symptoms of anaphylaxis such as trouble breathing, severe itching, skin rash or hives, or swelling of the face, lips, mouth or tongue should seek medical attention immediately.
The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds.
About Zepzelca (lurbinectedin)
Zepzelca is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and eventual cell death.4
The FDA approved Zepzelca under accelerated approval in June 2020 for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. The approval is based on overall response rate (ORR) and duration of response demonstrated in an open-label, monotherapy clinical study. In December 2021, Jazz and PharmaMar announced the initiation of LAGOON, a confirmatory Phase 3 clinical trial of Zepzelca for the treatment of patients with relapsed small cell lung cancer. If positive, LAGOON could confirm the benefit of Zepzelca in the treatment of small cell lung cancer (SCLC) when patients progress following 1L treatment with a platinum-based regimen and support full approval in the U.S.
Zepzelca is a prescription medicine used to treat adults with SCLC that has spread to other parts of the body (metastatic) and who have received treatment with chemotherapy that contains platinum, and it did not work or is no longer working. Zepzelca is approved based on response rate and how long the response lasted. Additional studies will further evaluate the benefit of Zepzelca for this use.
Important Safety Information for ZEPZELCA
Before receiving ZEPZELCA, tell your healthcare provider about all of your medical conditions, including if you:
have liver or kidney problems.
are pregnant or plan to become pregnant. ZEPZELCA can harm your unborn baby.
Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with ZEPZELCA.
You should use effective birth control (contraception) during treatment with and for 6 months after your final dose of ZEPZELCA.
Tell your healthcare provider right away if you become pregnant or think that you are pregnant during treatment with ZEPZELCA.
Males with female partners who are able to become pregnant should use effective birth control during treatment with and for 4 months after your final dose of ZEPZELCA.
Females who are breastfeeding or plan to breastfeed. It is not known if ZEPZELCA passes into your breastmilk. Do not breastfeed during treatment with ZEPZELCA and for 2 weeks after your final dose of ZEPZELCA. Talk to your healthcare provider about the best way to feed your baby during treatment with ZEPZELCA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain other medicines may affect how ZEPZELCA works.
What should I avoid while using ZEPZELCA?
Avoid eating or drinking grapefruit, or products that contain grapefruit juice during treatment with ZEPZELCA.
ZEPZELCA can cause serious side effects, including:
Low blood cell counts. Low blood counts including low neutrophil counts (neutropenia) and low platelet counts (thrombocytopenia) are common with ZEPZELCA, and can also be severe. Some people with low white blood cell counts may get fever, or an infection throughout the body (sepsis), that can cause death. Your healthcare provider should do blood tests before you receive each treatment with ZEPZELCA to check your blood cell counts.
Tell your healthcare provider right away if you develop:
fever or any other signs of infection
unusual bruising or bleeding
tiredness
pale colored skin
Liver problems. Increased liver function tests are common with ZEPZELCA, and can also be severe. Your healthcare provider should do blood tests to check your liver function before you start and during treatment with ZEPZELCA.
Tell your healthcare provider right away if you develop symptoms of liver problems including:
loss of appetite
nausea or vomiting
pain on the right side of your stomach area (abdomen)
Your healthcare provider may temporarily stop treatment, lower your dose, or permanently stop ZEPZELCA if you develop low blood cell counts or liver problems during treatment with ZEPZELCA.
The most common side effects of ZEPZELCA include:
Tiredness
low white and red blood cell counts
increased kidney function blood test (creatinine)
increased liver function blood tests
increased blood sugar (glucose)
nausea
decreased appetite
muscle and joint (musculoskeletal) pain
low level of albumin in the blood
constipation
trouble breathing
low levels of sodium and magnesium in the blood
vomiting
cough
diarrhea
These are not all of the possible side effects of ZEPZELCA.
Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Jazz Pharmaceuticals at 1-800-520-5568.
More information about Zepzelca, including Full Prescribing Information and Patient Information, is available here.
ZEPZELCA is a trademark of Pharma Mar, S.A. used by Jazz Pharmaceuticals under license.