On November 20, 2024 the National Medical Products Administration (NMPA) reported on its official website that the NMPA approved the listing of Zorifertinib Hydrochloride Tablets (trade name: Zorifer), a Class 1 innovative drug, developed by Alpha Biopharma (Press release, Alpha Biopharma, NOV 20, 2024, View Source [SID1234648530]). This product is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) accompanied with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutation and central nervous system (CNS) metastases.

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Zorifertinib is the first drug in the world to launch a registration clinical trial specifically for advanced NSCLC with CNS metastases and achieve remarkable results. It is also the only* EGFR tyrosine kinase inhibitor (EGFR-TKI) currently available that was explicitly designed as non-blood-brain barrier efflux protein substrates and can penetrate the blood-brain barrier 100%.

The EVEREST trial, an international multi-center randomized controlled phase III trial of Zorifertinib, demonstrated its superior ability to control intracranial lesions. The trial enrolled patients with more severe disease, most of whom had EGFR L858R mutations or had more than 3 intracranial lesions. Zorifertinib showed a significant benefit in overall progression-free survival (PFS), with intracranial PFS reaching 17.9 months, and it significantly reduced the risk of intracranial progression/death by 37% (P = 0.0018). Furthermore, Zorifertinib demonstrated consistent and significant benefits in subgroups of patients with intracranial symptoms, EGFR L858R mutations, and more than 3 intracranial lesions.

As the global lead Principal Investigator (PI) for the EVEREST study, Professor Wu Yilong from Guangdong Provincial People’s Hospital mentioned that while several drugs have been approved for EGFR mutated NSCLC, there is still a lack of clinical head-to-head randomized controlled studies specifically targeting drug therapy for lung cancer with CNS metastases. The EVEREST study is the world’s first large-scale registered international multi-center clinical trial for the treatment of lung cancer with CNS metastases, and it has achieved statistically significant positive results. In the study, the therapeutic advantages of Zorifertinib in various subgroups were observed, and it was verified that all people with EGFR mutated NSCLC and brain metastases could benefit from Zorifertinib therapy. Among patients who were treated with third-generation TKI after progression, a trend of benefit in overall survival was also observed, suggesting that the combination or sequential therapy with third-generation TKI is expected to bring a better prognosis.

Zhang Yong, CEO of Alpha Biopharma, stated that the company is dedicated to developing innovative drugs that are urgently needed in clinical practice. We have collaborated with AstraZeneca to develop Zorifertinib, aiming to address the unmet clinical needs of patients with lung cancer and CNS metastases. Zorifertinib has demonstrated its therapeutic value during the clinical stage and has received support from clinical experts and regulatory authorities. It has become the world’s first approved new generation EGFR-TKI specifically targeting lung cancer with CNS metastases. The company anticipates that Zorifertinib will significantly enhance patient care in the future, offering more effective treatments for individuals with lung cancer and brain metastases.

About Lung Cancer and Central Nervous System Metastasis

In China, lung cancer is the most common and deadliest malignant tumor. In 2022, there were about 1.06 million new cases of lung cancer diagnosed, leading to approximately 730,000 deaths, with non-small cell lung cancer (NSCLC) accounting for around 85% of all cases. In the Chinese NSCLC population, about 38.4% of patients have been found to have EGFR mutation-positive, which is identified as one of the driving genes for NSCLC formation.

Central nervous system metastasis is a common occurrence in NSCLC patients, with approximately 25% of EGFR mutation-positive NSCLC patients having CNS metastases at the time of initial diagnosis. Additionally, 20% to 65% of lung cancer patients will develop CNS metastases during the course of their disease. Poor blood-brain barrier permeability of therapeutic drugs is one of the reasons why patients experience CNS progression during treatment.

About Blood-Brain Barrier and Efflux Proteins

The blood-brain barrier is a protective shield that prevents drugs from entering the brain. It is made up of tightly packed brain capillary endothelial cells, surrounded by pericellular, astrocyte terminal, and basement membrane structures. This barrier has high resistance and low permeability, making it challenging for drugs to reach the brain. As a result, the brain can act as a safe haven for tumor cells, contributing to the progression of central nervous system (CNS) diseases.

The blood-brain barrier contains a large number of efflux proteins, such as P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP), which are crucial for drug resistance in the development of brain lesions and the survival of tumor stem cells.

Remarks:

The "only … currently available" in this article is valid as of the deadline of Oct. 10, 2024.

References

Cheng H, Perez-Soler R. Leptomeningeal metastases in non-small-cell lung cancer. Lancet Oncol. 2018 Jan;19(1):e43-e55.
Zhou Q, Yu Y, Xing L, et al. First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial. Med. Published online October 3, 2024.
Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. Journal of the National Cancer Center, 2024.
Duma N, Santana-Davila R, Molina JR. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin Proc. 2019, 94(8):1623-1640.
Zhang YL, Yuan JQ, Wang KF, et al. Threapleton D, Yang ZY, Mao C, Tang JL. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016 Nov 29;7(48):78985-78993.
Preusser M, Winkler F, Valiente M, Manegold C, Moyal E, Widhalm G, Tonn JC, Zielinski C. Recent advances in the biology and treatment of brain metastases of non-small cell lung cancer: summary of a multidisciplinary roundtable discussion. ESMO (Free ESMO Whitepaper) Open. 2018 Jan 26;3(1):e000262.
Oncology Physician Branch of Chinese Medical Doctor Association, Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care. Chinese Treatment Guidelines for Brain Metastases from Lung Cancer (2021 Edition). Chinese Journal of Oncology, 2021, 43(03): 269-281.
Shetty V, Babu S. Management of CNS metastases in patients with EGFR mutation-positive NSCLC. Indian J Cancer. 2019 Nov;56(Supplement):S31-S37.

On November 20, 2024 The Leukemia & Lymphoma Society (LLS) reported the company will present new data from its Beat AML Master Clinical Trial and Pediatric Acute Leukemia (PedAL) Master Clinical Trial at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, The Leukemia & Lymphoma Society, NOV 20, 2024, View Source;lymphoma-society-lls-data-at-ash-provides-glimpse-into-the-future-of-blood-cancer-treatment-302310609.html [SID1234648529]).

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The findings from LLS’s convened master clinical trials show great progress and are helping shape the treatment landscape for acute leukemias. Updated results show that more than half of a group of children with relapsed acute leukemias achieved remission after receiving a combination of treatments. Additional data indicate that IDH inhibitors as single agent or in combination with low-intensity therapies may be a viable treatment option for older adults with acute leukemias.

LLS will also support its more than 150 funded researchers, as well as more than a dozen current and former LLS Therapy Acceleration Program (TAP) biotech company partners, who will present the latest updates from their ongoing clinical trials.

"For 75 years, LLS has funded physician-scientists and researchers who take risks, think big and test bold ideas," says Lee Greenberger, Ph.D., LLS’s Chief Scientific Officer. "Our strategic investments have helped advance more than 70% of blood cancer treatments approved by the FDA over the past 20 years and I am encouraged to see how the latest data at ASH (Free ASH Whitepaper) will lead to remarkable advances for patients."

Health equity is also a major focus of findings from several investigators funded through the LLS Equity in Access and IMPACT grant programs, which:

Show that there’s significant underrepresentation of women and racial and ethnic minorities in clinical trial enrollment
Provide patient recommendations on how to address disparities in people living with multiple myeloma
Share insights on how to address barriers to opening clinical trials in a community-oncology setting
Demonstrate the disparities in access to care and services depending on the type of insurance coverage.
"LLS has an incredible track record of success across its research, health equity, patient advocacy, and education and support services," says E. Anders Kolb, M.D., The Leukemia & Lymphoma Society’s President and CEO. "The breadth of research we support every year at ASH (Free ASH Whitepaper) reinforces our commitment to improve and extend the lives of blood cancer patients and accelerate progress."

Gwen Nichols, M.D., LLS’s Chief Medical Officer, will join a panel at the Annual ASH (Free ASH Whitepaper) Clinicians in Practice luncheon on December 8, 2024, focused on the future of artificial intelligence in blood cancer.

Drs. Kolb, Nichols and Greenberger are available to provide perspectives on pivotal data presented at ASH (Free ASH Whitepaper), including the promise of menin inhibitors to change the leukemia treatment landscape.

Following is an overview of compelling data from LLS that will be presented at ASH (Free ASH Whitepaper):

Reshaping How Adults with Acute Myeloid Leukemia are Treated

Nearly 1,600 patients with AML have received genomic screening within seven days of diagnosis and more than 500 have enrolled in one of the many Beat AML precision treatment subtrials, which so far have targeted 15 distinct types of AML.

Patients enrolled in Beat AML have achieved improved survival and better quality of life compared to patients receiving standard-of-care chemotherapy.

Beat AML also recently opened its first clinical subtrial to investigate the safety and efficacy of lomonitinib (ZE46-0134) in patients with FLT3-mutated relapsed or refractory AML in partnership with Eilean Therapeutics.

These new findings from Beat AML subtrials will be presented at ASH (Free ASH Whitepaper):

Title & Poster Number

Date/Time

Location

Poster 1564 – Demographics, Characteristics, Survival and Outcomes in Older, Untreated, Acute Myeloid Leukemia Patients with NPM1 Mutations or KMT2A rearrangements from the Beat AML Master Clinical Trial

Saturday, Dec. 7, 2024

5:30-7:30 PM

San Diego Convention Center

Halls G-H

Poster 4324 – Outcomes and Survival in Newly Diagnosed, Older, Acute Myeloid Leukemia Patients from the Beat AML Master Trial in the Venetoclax/Azacitidine Age

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 4325 – IDH2 Mutation Is Associated with Favorable Outcome Among Older Adults with Newly Diagnosed Acute Myeloid Leukemia Treated with Lower-Intensity Therapy

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

LLS Executive Research Strategy Lead Ashley Yocum, Ph.D., is available to discuss Beat AML findings.

Revolutionizing the Treatment and Care of Children with Blood Cancer

LLS’s PedAL is fundamentally revolutionizing how children with pediatric leukemia are being treated while building a foundation that addresses major roadblocks to care.

LLS will present updated findings from the PedAL Screening Trial (APAL2020SC), which is actively enrolling in the U.S., Canada, Australia, and New Zealand. This LLS-convened and led screening trial assesses individual clinical and biological characteristics that can inform a family’s choice of standard treatment or enrolling in a clinical trial.

In addition to the PedAL Screening Trial, a treatment trial is open across 74 international sites. LLS anticipates the opening of a second PedAL global treatment trial soon.

Title & Poster Number

Date/Time

Location

Poster 4233 – Molecular Features, Treatments and Outcomes for Pediatric AML Patients from APAL2020SC Pediatric Acute Leukemia (PedAL) Screening Trial

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Chief Medical Officer Gwen Nichols, M.D., is available to provide updates on LLS PedAL and provide perspective on important clinical data coming out of ASH (Free ASH Whitepaper).

Driving the Latest Blood Cancer Developments Through Research Funding

Blood cancer physician-scientists and researchers are transforming the way we treat this disease, but they cannot do this groundbreaking work alone. LLS is helping to lead this charge by funding some of the most innovative research projects around the world focused on bringing blood cancer patients much needed new treatments.

LLS currently provides more than $300 million in academic biomedical research grants to investigators across 16 countries and 30 U.S. states to accelerate how we treat all blood cancers. LLS recently announced its latest round of multi-year grants, which includes research into the development of leukemia in children with Down syndrome.

Here are some of the latest research advances across a variety of blood cancers that several LLS grantees will present at ASH (Free ASH Whitepaper):

Title & Poster Number

Date/Time

Location

Oral 969 – Venetoclax Plus Azacitidine for Newly Diagnosed Younger Acute Myeloid Leukemia Patients Independent of Fitness for Intensive Chemotherapy

Monday, Dec. 9, 2024

5:00 PM

Manchester Grand Hyatt San Diego, Grand Hall B

Oral 321 – Machine Learning Derived Three-Parameter Prognostic Model for Survival in Patients with BPDCN

Saturday, Dec. 7, 2024

4:30 PM

Manchester Grand Hyatt San Diego, Seaport Ballroom EFGH

Oral 1011 – Combined Pirtobrutinib, Venetoclax, and Obinutuzumab As First-Line Treatment of Patients with Chronic Lymphocytic Leukemia (CLL)

Monday, Dec. 9, 2024

5:00 PM

Marriott Marquis San Diego Marina, Grand Ballroom 8-9

Oral 739 – Follicular Dendritic Cells Represent a Therapeutic Vulnerability in Early Follicular Lymphoma

Monday, Dec. 9, 2024

10:30 AM

Marriott Marquis San Diego Marina, Grand Ballroom 5-6

Oral 102 – Acute GvHD of the Gut Is Associated with Minor Histocompatibility Antigens Cross-Reactive Against Gut-Tropic Viral Epitopes

Saturday, Dec. 7, 2024

10:45 AM

San Diego Convention Center Ballroom 20CD

Oral 671 – A High-Fiber Dietary Intervention (NUTRIVENTION) in Precursor Plasma Cell Disorders Improves Biomarkers of Disease and May Delay Progression to Myeloma

Sunday, Dec. 8, 2024

5:30 PM

Marriott Marquis San Diego Marina, Pacific Ballroom Salons 24-26

Oral 755 – JAK2V617F Mutant MPN Cells Support Parallel Evolution of Independent Leukemic Clones

Monday, Dec. 9, 2024

11:30 AM

Manchester Grand Hyatt San Diego, Grand Hall C

Oral 857 – A Multiomic Analysis of Waldenstrom’s Macroglobulinemia Identifies Three Subtypes of Disease Based on Impaired Plasma Cell Differentiation

Monday, Dec. 9, 2024

3:45 PM

Marriott Marquis San Diego Marina, Pacific Ballroom Salons 18-19

Poster 3127 – Favorable Safety Profile and Durable Responses to Pmb-CT01 (BAFFR-CAR T Cell) Therapy in Patients with B-Cell Lymphomas Ineligible for or Who Failed CD19-Targeted Therapy, Including CD19-Negative Disease

Sunday, Dec. 8, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Addressing Healthcare Disparities Means a Better Future for Everyone with Blood Cancer

LLS believes every blood cancer patient and survivor should be able to access the care they need when they need it. LLS is addressing healthcare disparities to ensure everyone has a better future through three signature programs:

The Equity in Access Research Program, which provides funding for health services research that seeks to uncover and ultimately address the social, economic, and environmental disadvantages that stand in the way of patients with and survivors of a blood cancer accessing high-quality cancer care and services.
Influential Medicine Providing Access to Clinical Trials (IMPACT) provides funding to major cancer centers around the U.S. to collaborate with community-based hospitals and clinics to bring quality blood cancer clinical trials significantly closer to underrepresented patients.
Underrepresented Minority Medical Student (URM) Research programs, launched in 2023, aim to provide medical students from groups underrepresented in biomedical science the opportunity to participate in blood cancer research and benefit from mentorship that the program also provides. The URM program’s first grantee, Jennifer Lewis, is a co-author on an abstract that has developed a new CAR-T product that shows early promise in treating acute myeloid leukemia.
LLS proudly and gratefully acknowledges the leadership support of Royalty Pharma and the following companies for their support of the Equity in Access Research Program and other initiatives focused on reducing healthcare disparities in blood cancer care and treatment: AstraZeneca Pharmaceuticals LP, Lilly and Bristol Myers Squibb.

Title & Poster Number

Date/Time

Location

IMPACT Grants

Oral 784 – Bringing Hematological Malignancy Clinical Trials to Patients: Mayo Clinic LLS Impact

Monday, Dec. 9, 2024

11:15 AM

Marriott Marquis San Diego Marina, San Diego Ballroom AB

Poster 2322 – Chive-Impact: Establishing the Clonal Hematopoiesis and Inflammation in the Vasculature (CHIVE) Registry and Biorepository in Underserved Areas

Saturday, Dec. 7, 2024

5:30-7:30 PM

San Diego Convention Center

Halls G-H

Equity in Access

Oral 786 – Real-World Analysis of Insurer Rejection Rates for Specialty Oral Anticancer Prescriptions in a Nationwide Sample of Patients with Blood Cancer

Monday, Dec. 9, 2024

11:45 AM

Marriott Marquis San Diego Marina, San Diego Ballroom AB

Oral 792 – Impact of Fee-for-Service Versus Managed Care Medicare Insurance on the Quality of End-of-Life Care Among Older Adults with Blood Cancers

Monday, Dec. 9, 2024

11:45 AM

Manchester Grand Hyatt San Diego, Seaport Ballroom EFGH

Health Services

Poster 5100 – Disparities in phase 2 and 3 clinical trial enrollment for hematologic malignancies

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 5113 – Disparities in clinical trial participation among Medicare beneficiaries with hematologic malignancies from 2006 to 2019: a SEER-Medicare analysis

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Partner Projects

Poster 2383 – A Patient Perspective on Actionable Steps to Address Disparities in Healthcare Among US Patients with Multiple Myeloma

Saturday, Dec. 7, 2024

5:30-7:30 PM

San Diego Convention Center

Halls G-H

URM

Oral 371 – Development of CAR T Cells Targeting U5snRNP200 for the Treatment of Acute Myeloid and B-Lymphoid Leukemias

Saturday, Dec. 7, 2024

5:00 PM

Manchester Grand Hyatt San Diego, Grand Hall C

Senior Vice President of Education Services & Health Research Elisa Weiss, Ph.D., is available to provide perspective on health equity research presented at ASH (Free ASH Whitepaper).

Taking Risks to Accelerate the Development of Innovative Blood Cancer Therapies

LLS TAP provides funding to biotech companies to accelerate the development of innovative blood cancer treatments with the promise of changing the standard of care for blood cancer. As a strategic venture philanthropy program, LLS TAP can invest in research that venture capitalists find too risky.

Since 2017, five LLS TAP-supported therapies have been approved by the FDA or included in the National Comprehensive Cancer Network guidelines. Here are some of the latest research advances across a variety of blood cancers that several LLS TAP company partners will showcase at ASH (Free ASH Whitepaper):

Title & Poster Number

Date/Time

Location

Oral 214 – Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1-m or KMT2A-r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007

Saturday, Dec. 7

2:45 PM

San Diego Convention Center, Ballroom 20CD

Oral 980 – Results from the First Phase 1 Clinical Study of DR-01, a Non-Fucosylated Anti-CD94 Targeting Antibody in Patients with Relapsed/Refractory Cytotoxic Lymphomas: Dose Escalation and Optimization

Monday, Dec. 9, 2024

4:45 PM

Marriott Marquis San Diego Marina, Pacific Ballroom Salons 15-17

Oral 1008 – IO-202, a Novel Anti-LILRB4 Antibody, with Azacitidine for Hypomethylating Agent-Naive Chronic Myelomonocytic Leukemia: Phase 1b Expansion Cohort Results

Monday, Dec. 9, 2024

5:45 PM

Manchester Grand Hyatt San Diego, Grand Hall D

Poster 2876 – ICT01, an Investigational γ9δ2 T Cell Activator, Added to Azacitidine-Venetoclax Achieves Frequent and Early Complete Remissions in Adults with AML Unfit for Intensive Induction Chemotherapy: Interim Results from the Ongoing Open-Label, Randomized Phase 1 Study Eviction

Sunday, Dec. 8, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 3052 – Investigating the Novel Combination of the Innate Cell Engager (ICE) Acimtamig with Off-the-Shelf Allogeneic Natural Killer Cells AlloNK in Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Initial Results of the Phase 2 Luminice-203 Study

Sunday, Dec. 8, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 4265 – Encouraging Efficacy of Bexmarilimab with Azacitidine in Relapsed or Refractory MDS in Bexmab Ph1/2 Study

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 4395 – EO2463 Peptide Immunotherapy in Patients with Newly Diagnosed Asymptomatic Follicular Lymphoma Results in Monotherapy Objective Clinical Responses Linked with Anti-Peptide Specific CD8 Memory T Cell Responses: The EONHL1-20/Sidney Study

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 4433 – Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of KT-333, a Targeted Protein Degrader of STAT3, in Patients with Relapsed or Refractory Lymphomas, Leukemia, and Solid Tumors

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

On November 20, 2024 Vyriad, Inc., a clinical-stage biotechnology company developing the next generation of targeted genetic therapies, reported a strategic collaboration with Novartis to discover and develop in vivo chimeric antigen receptor (CAR) T-cell therapies (Press release, Vyriad, NOV 20, 2024, View Source [SID1234648528]).

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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 collaboration will leverage Vyriad’s active targeting lentiviral vector platform and Novartis expertise and leadership in cell therapy innovation. Novartis and Vyriad will focus on the identification and development of in vivo CAR-T cell therapy candidates to be clinically advanced by Novartis. Vyriad will receive an upfront payment, milestone payments, and tiered royalties on each program.

"Taking an in vivo approach to CAR-T cell therapies has the potential to transform the field," said Vyriad CEO Stephen J. Russell, M.D. Ph.D. "We believe our targeted delivery platform is poised to enable this vision for the industry and our collaboration with Novartis represents an exciting step forward in advancing the next generation of CAR-T cell treatments."

"As an industry pioneer in the field, we are committed to addressing unmet medical needs and making the transformative potential of CAR-T cell therapies available to more patients," said Jennifer Brogdon, Head of Cell & Gene Therapies at Novartis Biomedical Research. "We are excited to collaborate with Vyriad and combine their technology platform with Novartis expertise and capabilities to innovate and advance next-generation CAR-T cell therapies."

Vyriad’s targeted lentiviral vector platform provides T-cell specificity and activation in vivo, enabling delivery of CAR payloads to T cells in their natural environment. Through its viral vector engineering acumen, Vyriad developed a lentiviral delivery system with the potential to target and transduce resting T cells and reprogram them while still inside the body to become potential treatments for patients.

On November 20, 2024 Jazz Pharmaceuticals reported the U.S. Food and Drug Administration (FDA) accelerated approval of Ziihera (zanidatamab-hrii) 50mg/mL for injection for intravenous use for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test (Press release, Jazz Pharmaceuticals, NOV 20, 2024, View Source [SID1234648527]). Ziihera was approved under accelerated approval based on a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months as determined by independent central review (ICR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 The Phase 3 HERIZON-BTC-302 confirmatory trial is ongoing to evaluate zanidatamab in combination with standard-of-care therapy versus standard-of-care therapy alone in the first-line setting for patients with HER2-positive BTC.

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!

"BTC is a devastating disease with a poor prognosis and five-year survival rates under five percent in the metastatic setting. Patients with unresectable or metastatic HER2-positive BTC have had a high unmet need with limited treatment options and few approved therapies," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "The approval of Ziihera, which previously received Breakthrough Therapy Designation from the FDA for this indication, is an important advance and offers the first and only dual HER2-targeted bispecific antibody and chemotherapy-free treatment for patients living with BTC. We look forward to advancing research of zanidatamab in BTC and other HER2-expressing solid tumors, with the goal of improving outcomes for more people diagnosed with these difficult-to-treat HER2-positive cancers."

The FDA approval of Ziihera is based on compelling data from the HERIZON-BTC-01 trial, which included the evaluation of zanidatamab as a single agent in previously treated HER2-positive (as determined by Roche Diagnostic’s PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody companion diagnostic) BTC and is the largest Phase 2b clinical trial to date specifically for this patient population. The trial achieved its primary endpoint of confirmed objective response rate (cORR) by independent central review (ICR) and results were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2023, published in The Lancet Oncology, and included in the 2023 Best of ASCO (Free ASCO Whitepaper) program. Longer follow-up data showing improvement upon previously reported DOR were reported at the ASCO (Free ASCO Whitepaper) Annual Meeting 2024.1

"As a clinical investigator and medical oncologist focused on advancing the care of patients with biliary tract and liver cancers, I have experienced firsthand the significant unmet need for effective therapies for patients with these diseases," said Dr. James Harding, associate attending, Gastrointestinal Oncology and Early Drug Development Services, at Memorial Sloan Kettering Cancer Center. "Zanidatamab has demonstrated antitumor activity and is now a new option for patients with HER2-positive biliary tract cancer. I look forward to continued and successful drug development for patients with biliary tract cancer."

"Metastatic biliary tract cancer, BTC, places a significant burden on patients, affecting their quality of life and their emotional and mental well-being, as well as that of their families," said Stacie Lindsey, CEO and founder of the Cholangiocarcinoma Foundation. "The approval of Ziihera offers a promising treatment option. It provides patients and their loved ones the possibility of more time together and an improved quality of life, which is invaluable for the entire BTC community."

The efficacy of Ziihera was evaluated in 62 patients with HER2-positive (IHC 3+ by central assessment) BTC in Cohort 1 of HERIZON-BTC-01, with major efficacy outcome measures of ORR and DOR as determined by ICR according to RECIST (Response Evaluation Criteria in Solid Tumors) v1.1.1 The study demonstrated an ORR of 52% [95% confidence interval (CI): 39, 65)] with a Kaplan Meier (KM) estimated median DOR of 14.9 months [95% CI: 7.4-not estimable] by ICR.1

Boxed Warning for Embryo-fetal toxicity: Exposure to Ziihera during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.1

The safety profile for Ziihera has been demonstrated in 80 patients in the HERIZON-BTC-01 trial. Serious adverse reactions occurred in 53% of patients who received Ziihera. The most common adverse reactions in patients who received Ziihera (≥ 20%) were diarrhea, infusion-related reaction, abdominal pain, and fatigue. Serious adverse reactions in > 2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received Ziihera. Permanent discontinuation due to an adverse reaction occurred in 2.5% of patients who received Ziihera.1 See additional safety information below and full prescribing information View Source

The confirmatory, global, randomized Phase 3 trial HERIZON-BTC-302 (NCT06282575) is ongoing and is evaluating zanidatamab in combination with standard-of-care therapy versus standard-of-care therapy alone in the first-line setting for patients with HER2-positive BTC. Continued approval for Ziihera may be contingent upon verification and description of clinical benefit in this confirmatory trial.

Zanidatamab is also being investigated in a number of additional tumor types, including Phase 3 trials in gastroesophageal adenocarcinomas (GEAs) and metastatic breast cancer (mBC). The HERIZON-GEA-01 trial evaluating the potential of zanidatamab plus chemotherapy with or without tislelizumab as first-line treatment for patients with advanced/metastatic HER2-positive GEAs. The EmpowHER-303 trial is evaluating the potential of zanidatamab in combination with physician’s choice chemotherapy for the treatment of HER2-positive mBC for patients who have progressed on, or are intolerant to, previous trastuzumab deruxtecan treatment.

About the Phase 2b HERIZON-BTC-01 Trial
The Phase 2b HERIZON-BTC-01 trial of zanidatamab was an open-label, global Phase 2b study, which enrolled 87 patients with HER2-amplified, locally advanced unresectable or metastatic BTC (gallbladder cancer, intra-/extra-hepatic cholangiocarcinoma) into 2 cohorts and included 62 patients with HER2 IHC 3+ BTC. The trial evaluated zanidatamab (20 mg/kg IV every 2 weeks) in patients who had received prior gemcitabine-containing therapy. Patients with prior HER2-targeted therapy use were excluded from the trial. All patients were required to have HER2 status confirmed with tissue samples by a central lab. Patients (n=87) were assigned into two cohorts based on tumor IHC status: Cohort 1 (n=80) included patients who were IHC 2+/3+ (HER2-amplified) and Cohort 2 (n=7) included patients who were IHC 0/1+. Tumors were assessed every 8 weeks per RECIST v1.1. The primary endpoint was ORR by independent central review (ICR) in Cohort 1, with secondary endpoints including other efficacy and safety outcomes.

Investor Webcast on Wednesday, December 11, 2024
The company will host a webcast on Wednesday, December 11, 2024, at 4:30 p.m. ET / 9:30 p.m. GMT to provide investors an overview of clinical data, patient need and commercialization strategy for Ziihera. The webcast will include commentary from a leading BTC expert and the company’s senior management.

Audio webcast/conference call:
U.S. Dial-In Number: +1 800 715 9871
Ireland Dial-In Number: +353 1800 943 926
Additional global dial-in numbers are available here.
Passcode: 4898380

A live webcast of the presentation may be accessed from the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. Please connect to the website prior to the start of the presentation to ensure adequate time for any software downloads that may be necessary to listen to the webcast. An archive of the webcast will be available for at least one week following the presentation on the Investors section of the company’s website at www.jazzpharmaceuticals.com.

More information about Ziihera, the Full Prescribing Information, including Boxed Warning and Patient Information, is available here.

About Ziihera (zanidatamab-hrii)
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab-hrii with HER2 results in internalization leading to a reduction of the receptor on the tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.1 In the United States, Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.1 The U.S. Food and Drug Administration (FDA) granted accelerated approval for this indication based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1

Zanidatamab is not approved anywhere else in the world.

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 FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified 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 1L 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.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY
Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients
of the risk and need for effective contraception.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity
ZIIHERA can cause fetal harm when administered to a pregnant woman. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA.

Left Ventricular Dysfunction

ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). LVEF declined by >10% and decreased to <50% in 4.3% of 233 patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation of ZIIHERA was reported in 0.9% of patients. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7). LVD resolved in 70% of patients.

Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions.

The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%.

Infusion-Related Reactions
ZIIHERA can cause infusion-related reactions (IRRs). An IRR was reported in 31% of 233 patients treated with ZIIHERA as a single agent in clinical studies, including Grade 3 (0.4%), and Grade 2 (25%). IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day.

Prior to each dose of ZIIHERA, administer premedications to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use.

If an IRR occurs, slow, or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs.

Diarrhea

ZIIHERA can cause severe diarrhea.

Diarrhea was reported in 48% of 233 patients treated in clinical studies, including Grade 3 (6%) and Grade 2 (17%). If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue ZIIHERA based on severity.

ADVERSE REACTIONS

Serious adverse reactions occurred in 53% of 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA. Serious adverse reactions in >2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA.

The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%).

USE IN SPECIFIC POPULATIONS

Pediatric Use

Safety and efficacy of ZIIHERA have not been established in pediatric patients.

Geriatric Use

Of the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older.

No overall differences in safety or efficacy were observed between these patients and younger adult patients.

About Biliary Tract Cancer
BTC, including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers globally and are often associated with a poor prognosis.2,3 The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers. Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.4,5,6,7

On November 20, 2024 Rakovina Therapeutics Inc. (TSX-V: RKV) ("Rakovina" or the "Company"), a biopharmaceutical company committed to advancing new cancer therapies based on novel DNA-damage response targeting technologies, reported an upcoming poster presentation highlighting preliminary results of its Deep Docking and generative Artificial Intelligence (AI) drug development program at the Neuro-Oncology Annual Meeting in Houston, Texas, on November 22, 2024 (Press release, Rakovina Therapeutics, NOV 20, 2024, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-announces-upcoming-poster-presentation-at-the-29th-annual-society-for-neuro-oncology-meeting-in-houston-texas [SID1234648524]).

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The poster will be available to conference attendees as virtual e-posters on the virtual meeting platform on November 22, 2024.

Poster Details:

Title: Utilizing Artificial Intelligence for the Discovery of Novel PARP1-Selective Inhibitors for Use Against Brain Tumors
Presentation Date: November 22, 2024
Session: 7:30pm CST
Abstract Number: DDDR-15
About the Annual Society for Neuro-Oncology (SNO) Annual Meeting

The SNO Annual Meeting is the premier global event in neuro-oncology, bringing together over 2,600 researchers, clinicians, and scientists from more than 40 countries to advance the field of neuro-oncology. This influential conference will feature leading experts in oncology, providing a platform for the latest research, treatments, and innovations. The 2024 meeting will take place at the George R. Brown Convention Center in Houston, Texas, from November 21-24. For more information, visit: View Source