On December 9, 2021 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate the mutant tumor suppressor protein, p53, reported that the U.S. Food and Drug Administration (FDA) has removed the full clinical hold on the Company’s clinical trial evaluating the combination of its lead compound, eprenetapopt, with acalabrutinib or with venetoclax and rituximab in lymphoid malignancies (Press release, Aprea, DEC 9, 2021, View Source [SID1234596654]).

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"We are pleased to have addressed the FDA’s concerns and receive clearance to proceed with future clinical study of eprenetapopt in non-Hodgkin’s lymphomas," said Eyal Attar, M.D., Chief Medical Officer of Aprea Therapeutics. "We look forward to continued evaluation of eprenetapopt as a therapeutic option for these patients with unmet medical need."

On December 9, 2021 Investigators from US Oncology Research, The US Oncology Network (The Network), and OntadaTM reported that it will share results from more than 30 studies exploring areas such as diffuse large B cell lymphoma, non-Hodgkin lymphoma, multiple myeloma and hematological adverse event management in the community oncology setting at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, US Oncology, DEC 9, 2021, View Source [SID1234596681]). The ASH (Free ASH Whitepaper) Annual Meeting, a leading scientific event in malignant and non-malignant hematology, will take place in Atlanta, Georgia and virtually from Dec. 11-14, 2021.

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"We are making tremendous strides in caring for a wide array of hematological malignancies, including hard-to-treat blood cancers, and have much more to offer patients than in years past. However, there is still need for advances," said Robert L. Coleman, MD, FACOG, FACS, chief scientific officer, US Oncology Research. "We are excited about presenting our latest findings and coming back together with the community as we continue to learn, collaborate and innovate towards improved patient outcomes."

In a late-breaking abstract session on Tuesday, Dec. 14 from 9:00 am to 10:30 am ET, results will be presented from "The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma."

"Approximately 40 percent of patients with newly diagnosed diffuse large B-cell lymphoma are not cured with the current standard of care regimen known as R-CHOP," said study co-author John Burke, MD, a hematologist with Rocky Mountain Cancer Centers, a practice in The Network. "In the Phase 3 POLARIX study, we compared a combination of the CD79b-targeting antibody–drug conjugate, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisone, or pola-R-CHP, with R-CHOP. The results of the POLARIX study may have significant implications for the way we treat diffuse large B-cell lymphoma in the front-line setting in the future and look forward to the findings being shared at the ASH (Free ASH Whitepaper) Meeting."

Additionally, Dr. Burke will present an abstract titled, "Efficacy and Safety of Umbralisib, Ublituximab (U2), and U2 Plus Bendamustine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)," in an oral presentation Sunday, Dec. 12 at 5:30 pm.

"Patients with relapsed or refractory DLBCL generally have a poor prognosis, particularly if they are not candidates for autologous stem cell transplantation or experience relapse following approved CAR-T therapies. In the UNITY-NHL study, we systematically explored the efficacy and tolerability of the PI3K-d/CK1-e inhibitor, umbralisib, alone, and in combination with the glycoengineered anti-CD20 monoclonal antibody ublituximab, followed by a cohort treated with umbralisib, ublituximab and bendamustine," said lead author Dr. Burke. "We found that the triplet regimen was effective and well tolerated in patients with relapse or refractory DLBCL who were unsuitable for transplant or who had relapsed following transplant."

In an oral abstract session on Monday, Dec. 13 at 4:45 pm, results will be presented from the study, "Completed Induction Phase Analysis of Magnify: Phase 3b Study of Lenalidomide + Rituximab (R2) Followed By Maintenance in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma."

"Unfortunately, people with relapsed indolent non-Hodgkin lymphoma have limited standard treatment options," said study co-author David Andorsky, MD, hematologist with Rocky Mountain Cancer Centers. "Therefore, our analysis from the induction phase of the Phase 3b MAGNIFY trial which provides additional evidence that lenalidomide combined with rituximab is active with a tolerable safety profile in a wide range of patients with relapsed or refractory disease is encouraging."

Jerome Goldschmidt, MD, oncologist at Blue Ridge Cancer Care, a practice in The Network, will present results during a poster presentation titled, "Understanding Hematological Adverse Event Management through Health Care Resource Utilization, Costs, and Treatment Patterns of Patients with Extensive-Stage Small Cell Lung Cancer Treated in the Community Oncology Setting," on Saturday, Dec. 11 from 5:30 pm to 7:30 pm. Dr. Goldschmidt, lead author of the abstract, worked with Ontada researchers on this retrospective, observational study. Ontada is an oncology real-world data and evidence, clinical education and provider technology business dedicated to improving the lives of cancer patients.

"Our study found that there is significant burden of myelosuppressive hematological adverse events among extensive stage small cell lung cancer patients in the community oncology setting. Notably, patients with grade ≥3 hematological adverse events appear to have more dose reductions, treatment delays and healthcare service utilizations than those without," said Dr. Goldschmidt. "Future research should strive to understand the full scope of hematologic adverse event management and define the role therapies that protect bone marrow from these adverse events can play in reducing this burden."

Robert Rifkin, MD, medical director of biosimilars for McKesson, associate chair of hematology research and myeloma disease lead for The US Oncology Network, and hematologist with Rocky Mountain Cancer Centers, co-authored an analysis of outcomes among people with triple-class refractory multiple myeloma titled, "Real-World Treatment Patterns and Clinical, Economic, and Humanistic Burden in Triple-Class Refractory Multiple Myeloma: Analysis of the Connect Multiple Myeloma (MM) Disease Registry." The oral presentation will take place on Saturday, Dec. 11 at 10:00 am.

"Treatment resistance remains a challenge for most multiple myeloma patients and their outcomes and health-related quality of life worsens with each line of therapy. Patients who are refractory to immunomodulatory drugs, proteasome inhibitors and anti-CD38 antibodies, or triple-class refractory, have an especially bleak prognosis and high disease burden," said Dr. Rifkin. "Data presented from the ongoing prospective Connect MM Disease Registry confirm that people with triple-class refractory multiple myeloma experience poor survival, substantial hospitalizations and a clinically meaningful decline in health-related quality of life and suggest that novel tolerable and efficacious therapeutic agents are urgently needed to address the burden of illness in triple-refractory multiple myeloma."

The full schedule of affiliated data presentations, including timing and author information, can be found here. For more information or to interview a trial investigator, contact Claire Crye at 281.825.9927 or [email protected] or Edie DeVine at 209.814.9564 or [email protected].

On December 9, 2021 Seattle Cancer Care Alliance (SCCA), the only National Comprehensive Cancer Network (NCCN)-designated cancer center in Washington state, reported that more than 20 of the organization’s clinicians will showcase new research at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), taking place December 11-14, 2021, in Atlanta (Press release, Seattle Cancer Care Alliance, DEC 9, 2021, View Source [SID1234596708]).

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SCCA clinicians and researchers will unveil findings on areas of investigation into treatments for patients with various hematological malignancies, including lymphoma, leukemia and myeloma. Clinicians will discuss findings on CAR-T therapies targeting CD20 cells, multiple myeloma and chronic lymphocytic leukemia. Key research also includes findings on hematopoietic stem cell transplant (HCT) and outcomes and utilization for a range of treatments.

"Our team at Seattle Cancer Care Alliance is committed to understanding, developing and advancing cutting-edge cancer treatments," said Nancy Davidson, MD, president and executive director of SCCA. "Our researchers and clinicians are known leaders in the hematological clinical research space; we are proud of their work and continued contributions to this space. We look forward to energized discussion on the implications of the research presented and the role the research plays in contributing to expanded treatment options for patients."

For more information about SCCA physician-researchers presenting their pioneering research at the 63rd ASH (Free ASH Whitepaper) annual meeting, visit View Source

Below is a list of SCCA’s lead abstracts and presentations:

CAR-T Therapies:

Abstract: 3872 – Safety and Efficacy of Third Generation CD20 Targeted CAR-T (MB-106) for Treatment of Relapsed/Refractory B-NHL and CLL

SCCA Author: Mazyar Shadman, MD, MPH
Abstract: 2815 – Pharmacodynamic Analysis of CAR-T Cell Persistence in Patients with Hematologic Malignancies Treated with NKTR-255, an IL-15 Receptor Agonist That Enhances CD8+ T-Cells: Preliminary Results from a Phase 1 Study

SCCA Author: Alexandre V. Hirayama, MD
Abstract: 1749 – Long-Term Follow-up and Single-Cell Multiomics Characteristics of Infusion Products in Patients with Chronic Lymphocytic Leukemia Treated with CD19 CAR-T Cells

SCCA Author: Alexandre V. Hirayama, MD
Abstract: 551 – Safety and Efficacy of Fully Human BCMA CAR T Cells in Combination with a Gamma Secretase Inhibitor to Increase BCMA Surface Expression in Patients with Relapsed or Refractory Multiple Myeloma

SCCA Author: Andrew J. Cowan, MD
Abstract: 905 – Clinical Translation of SC-DARIC33: A Pharmacologically Controlled CD33-Targeted Anti-AML CAR T Cell Product Regulated By Low Nanomolar Concentrations of Rapamycin

SCCA Author: Jacob S. Appelbaum, MD, PhD
Abstract: 470 – SCRI-CAR19x22v2 T Cell Product Demonstrates Bispecific Activity in B-ALL

SCCA Author: Corinne Summers, MD
Hematopoietic Stem Cell Transplant (HCT):

Abstract: 645 – Donor Bone Marrow Derived Macrophage Engraftment into the Central Nervous System of Allogeneic Transplant Patients

SCCA Author: Keith R. Loeb, MD, PhD
Abstract: 646 – Non-Genetic Determinants of Clonotypic T Cell Expansion Following Allogeneic Stem Cell Transplant

SCCA Author: Albert C. Yeh, MD
Abstract: 2868 – COVID-19 in Pediatric Hematopoietic Cell Transplant Recipients: A CIBMTR Study

SCCA Author: Neel S. Bhatt, MBBS, MPH
Abstract: 648 – Early Cytomegalovirus Reactivation after Allogenic Bone Marrow Transplantation Is Associated with the Loss of Recipient-Derived Humoral Immunity and Is Reduced By IL-6 Inhibition

SCCA Author: Ping Zhang, MD
Treatments of Hematological Malignancies:

Abstract: 1208 – The Efficacy and Safety of Low-Dose Inotuzumab Ozogamicin in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia: Interim Results of a Phase 4 Study

SCCA Author: Ryan D. Cassaday, MD
Abstract: 34 – A Phase 1/2 Trial of Cladribine, High-Dose Cytarabine, G-CSF, and Dose-Escalated Mitoxantrone (CLAG-M) Plus Gemtuzumab Ozogamicin in Adults with Newly-Diagnosed Acute Myeloid Leukemia (AML) or Other High-Grade Myeloid Neoplasm

SCCA Author: Roland B. Walter, MD, PhD, MS
Abstract: 813 – Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Follicular Lymphoma: Primary Analysis from a Phase 2 Study (CITADEL-203)

SCCA Author: Ryan C. Lynch, MD
Abstract: 233 – Concurrent Pembrolizumab with AVD for Untreated Classical Hodgkin Lymphoma

SCCA Author: Ryan C. Lynch, MD
Abstract: 1410 – Phase 2 Study of Zanubrutinib in BTK Inhibitor-Intolerant Patients (Pts) with Relapsed/Refractory B-Cell Malignancies

SCCA Author: Mazyar Shadman, MD, MPH
Abstract: 1363 – Oral Ixazomib in Untreated Follicular Lymphoma Permits COVID-19 Vaccine Response and Its Efficacy Is Associated with Clinical Factors and Gene Expression Signatures

SCCA Author: Solomon A. Graf, MD
Abstract: 799 – Global Proteomic Profiling Identifies Novel Prognostic Factors in Undifferentiated Leukemia Blasts from Patients with NPM1 Mutations: A Previously Unreported Approach to Biomarker Discovery from the Fred Hutch and SWOG

SCCA Author: Derek L. Stirewalt, MD
Abstract: 403 – CD22 CAR Optimization for Improved in-Human Activity Following Inadequate CD22 CAR Activity in Phase 1 Clinical Trial PLAT-04

SCCA Author: Corinne Summers, MD
Abstract: 2339 – Infectious Complications after Intensive Chemotherapy with CLAG-M or ‘7+3’ for Adults with Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms

SCCA Author: Anna B. Halpern, MD
Abstract: 3341 – Development of Astatine-211 (211At)-Based Anti-CD123 Radioimmunotherapy for Acute Leukemias and Other CD123+ Hematologic Malignancies

SCCA Author: Johnnie J. Orozco, MD, PhD
Abstract: 2745 – TIG-007: Study of EOS884448/GSK4428859A Alone, and in Combination with Iberdomide with or without Dexamethasone, in Participants with Relapsed or Refractory Multiple Myeloma

SCCA Author: Leona Holmberg, MD, PhD
Abstract: 3909 – Patient-Reported Outcomes (PROs) Among Patients with Steroid-Refractory or -Dependent Chronic Graft-vs-Host Disease (cGVHD) Randomized to Ruxolitinib (RUX) vs Best Available Therapy (BAT)

SCCA Author: Stephanie J. Lee, MD, MPH
Abstract: 2094 – Absence of Hyperactivation of Fibrinolysis Explains the Lack of Hemostatic Efficacy of Prophylactic Tranexamic Acid (TXA) in Hypoproliferative Thrombocytopenia

SCCA Author: Terry B. Gernsheimer, MD
Abstract: 1609 – The IL-2/IL-15 Mimetic NL-201 Prevents Myeloma Relapse after ASCT By Expanding Highly Cytolytic T Cells in the Bone Marrow That Are Resistant to Exhaustion

SCCA Author: Simone A. Minnie, PhD
Abstract: 328 – The Combination of Anti-Tigit and Lenalidomide Promotes Synergistic Myeloma-Specific Immunity after ASCT

SCCA Author: Simone A. Minnie, PhD

On December 9, 2021 QIAGEN (NYSE: QGEN; Frankfurt Prime Standard: QIA) and Denovo Biopharma LLC reported a collaboration to develop a blood-based companion diagnostic (CDx) test to identify patients expressing Denovo Genomic Marker 1 (DGM1TM) who are likely to respond to Denovo’s investigational cancer drug DB102TM for treatment of diffuse large B-cell lymphoma (DLBCL), one of the most common lymphoid cancers (Press release, Qiagen, DEC 9, 2021, View Source [SID1234605581]).

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Under the agreement, QIAGEN will develop a diagnostic assay that can detect the Denovo Genomic Marker 1 (DGM1TM) in DLBCL patients, a biomarker discovered by Denovo that predicts the responsiveness to DB102. Also known as enzastaurin, Denovo’s drug is a first-in-class investigational small molecule inhibitor of PKC-beta, a protein whose presence has been compellingly linked to DLBCL cases.

"We are proud to be at the cutting edge of precision medicine, a quantum leap from traditional one-drug-fits all medicine," said Jonathan Arnold, Vice President, Head of Oncology and Precision Diagnostics at QIAGEN. "Our molecular testing expertise will help Denovo to develop the use of the DGM1 marker with the DB102 drug for patients with DLBCL."

QIAGEN will develop a real-time qualitative PCR companion diagnostic for the QIAGEN Rotor-Gene Q MDx instrument and apply for premarket approval (PMA) with the US-based Food and Drug Administration (FDA). The goal is to get the PMA for the test contemporaneously with Denovo receiving new drug application (NDA) approval for its DB102. The drug and the DGM1 marker are currently in a phase III trial, called ENGINE, on newly diagnosed, high-risk DLBCL patients.

"As our ENGINE trial nears completion, we are pleased to be working with QIAGEN on commercial development of our DB102 program to enable patients and physicians to potentially benefit from DB102 treatment," said Xiao-Xiong Lu, Denovo’s Chief Technology Officer. "As a pioneer in precision medicine QIAGEN brings extensive experience in companion diagnostics, including ten FDA-approved tests."

QIAGEN is the global leader in collaborations with pharmaceutical and biotechnology companies to co-develop companion diagnostics, which detect clinically relevant genetic abnormalities to provide insights that guide clinical decision-making in diseases such as cancer. The company has an unmatched depth and breadth of technologies from next-generation sequencing (NGS) to polymerase chain reaction (PCR) for companion diagnostic development. Its ten PCR-based CDx tests with FDA approval include therascreen EGFR for non-small cell lung cancer, therascreen KRAS for colorectal cancer, therascreen FGFR for urothelial cancer, therascreen PIK3CA for breast cancer based on tissue or plasma samples and the therascreen BRAF kit for colorectal cancer.

Currently, QIAGEN is working under master collaboration agreements with more than 25 companies to develop and commercialize companion diagnostic tests for their drug candidates – a deep pipeline of potential future products to advance Precision Medicine for the benefit of patients.

On December 9, 2021 AstraZeneca reported that New results from the DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a higher progression-free survival (PFS) and objective response rate (ORR) in pre-specified patient subgroups compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane (Press release, AstraZeneca, DEC 9, 2021, View Source [SID1234596655]).

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Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo).

A similar PFS and ORR benefit was observed in exploratory analyses in patients defined by stable brain metastases, hormone receptor status, number of prior lines of therapy, prior pertuzumab treatment, or status of visceral metastasis. Results were presented in an oral presentation at the 2021 San Antonio Breast Cancer Symposium (SABCS).

In patients with stable brain metastases at baseline, treatment with Enhertu resulted in higher PFS compared to T-DM1 (PFS by blinded independent central review (BICR) hazard ratio [HR] 0.25; 95% confidence interval [CI] 0.13-0.45). Additionally, in this subgroup, Enhertu improved PFS to a median of 15 months versus 3 months for T-DM1.

Sara Hurvitz, MD, FACP, medical oncologist, professor of medicine, and director of the Breast Cancer Clinical Trials Program in the division of hematology-oncology at the David Geffen School of Medicine at UCLA, and medical director for the Clinical Research Unit at the UCLA Jonsson Comprehensive Cancer Center in Santa Monica, CA, said: "The main goals in the treatment of HER2-positive metastatic breast cancer, including those with stable brain metastases are to improve symptoms, stabilise or reduce the tumour size and improve overall survival. The higher progression-free survival seen in DESTINY-Breast03 in the subgroup of patients with stable brain metastases are encouraging, and underscores the excitement around another potential treatment option for patients who have experienced disease progression on currently available therapies."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "More treatment options are needed to delay progression and extend survival for patients with HER2-positive metastatic breast cancer who develop brain metastases. These additional analyses from DESTINY-Breast03 reinforce the potential of Enhertu with similar benefits in the different subgroups."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "These additional analyses from DESTINY-Breast03 continue to demonstrate the benefit of Enhertu compared to T-DM1 in patient subgroups, including 15-month progression-free survival in those with stable brain metastases, illustrating the potential of this treatment to become the new standard of care in patients with previously treated HER2-positive metastatic breast cancer. These data will support our ongoing conversations with global health authorities to realise our commitment to bring Enhertu to patients with previously treated HER2-positive breast cancer earlier in the metastatic setting."

Between 30 to 50% of patients with HER2-positive metastatic breast cancer will develop brain metastases, and while increased availability of HER2 therapies has improved systemic disease control, prognosis following the development of brain metastases remains poor.1-5

Confirmed ORR for patients with stable brain metastases at baseline was 67.4% with Enhertu versus 20.5% with T-DM1. A retrospective, non-prespecified evaluation of intracranial response among patients with stable brain metastases who received scans at baseline provided preliminary evidence that treatment with Enhertu is associated with intracranial tumour response and reduction in Central Nervous System disease with 10 (27.8%) complete responses (CR) and 13 (36.1%) partial responses (PR) compared to one (2.8%) CR and 11 (30.6%) PRs in those treated with T-DM1.

Summary of DESTINY-Breast03 subgroup analyses

Summary of DESTINY-Breast03 subgroup analyses table
CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; NE, not estimable; ORR, objective response rate
a Absolute ORR Difference, % [Enhertu-T-DM1]
b Patients with rapid progression on (neo)adjuvant therapy were included. Line of therapy does not include endocrine therapy.

The safety profile of the most common adverse events with Enhertu in DESTINY-Breast03 remains consistent with previous clinical trials of Enhertu in breast cancer with no new safety concerns identified. Adjudicated drug-related interstitial lung disease or pneumonitis was reported in 27 patients (10.5%) treated with Enhertu and five patients (1.9%) treated with T-DM1 overall, with no Grade 4 or 5 events.

Based on the primary results of DESTINY-Breast03, Enhertu received its fourth Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens in September 2021.

Enhertu is approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in more than 30 countries based on the results from the DESTINY-Breast01 trial.

Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

Notes

DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate, duration of response, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.6 More than two million patients with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.6 Approximately one in five cases of breast cancer are considered HER2-positive.7

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers.8 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.9

Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.1 Additionally, it is estimated that 30 to 50% of patients will develop brain metastases, and while increased availability of HER2 therapies has improved systemic disease control, prognosis following development of brain metastases remains poor.1-5 More treatment options are needed to further delay progression and extend survival.1-4

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4 mg/kg) is also approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

A Type II Variation is currently under review by the European Medicines Agency (EMA) for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior anti-HER2-based regimen.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.

Enhertu received its fourth BTD in the US, which was for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens.

Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and investigational agents next-generation oral SERD and camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.