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BeiGene Announces PDUFA Goal Date Extension for U.S. sNDA for BRUKINSA for the Treatment of CLL/SLL

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The FDA extended the PDUFA goal date to allow time to review additional clinical data submitted by BeiGene, which was deemed a major amendment to the sNDA. The submission included final response analysis from the global ALPINE clinical trial showing BRUKINSA demonstrated superiority versus ibrutinib in overall response rate (ORR) as assessed by an Independent Review Committee (IRC) in adult patients with relapsed or refractory (R/R) CLL or SLL. This final response analysis was announced by the company on April 11, 2022.

"We will continue to work closely with the FDA to facilitate the review of our sNDA for BRUKINSA in CLL/SLL," said John V. Oyler, Co-Founder, Chairman and CEO of BeiGene. "We are confident that the data in our filing demonstrate BRUKINSA’s potential in the treatment of CLL/SLL and are committed to bringing this important medicine to CLL/SLL patients in the U.S. as soon as possible following regulatory approval."

The sNDA filing in CLL/SLL includes data from two pivotal randomized Phase 3 studies and eight supportive studies in B-cell malignancies. The two global Phase 3 trials of BRUKINSA in CLL/SLL are: SEQUOIA (NCT03336333) comparing BRUKINSA to bendamustine and rituximab in treatment-naïve (TN) patients and ALPINE (NCT03734016) comparing BRUKINSA to ibrutinib in relapsed or refractory (R/R) patients. Additionally, the SEQUOIA study enrolled patients with deletion 17p in a non-randomized arm evaluating BRUKINSA monotherapy in this high-risk population. ALPINE and SEQUOIA enrolled patients from a total of 17 countries, including the United States, multiple countries in Europe, China, Australia, and New Zealand. Interim results from the ALPINE trial and the SEQUOIA trial were reported at the 26th European Hematology Association (EHA) (Free EHA Whitepaper) (EHA2021) Virtual Congress in June 2021 and at the 63rd American Society for Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021, respectively.

About ALPINE

ALPINE is a randomized, global Phase 3 trial (NCT03734016) comparing BRUKINSA against ibrutinib in previously treated patients with relapsed or refractory chronic lymphocytic leukemia CLL or SLL. In the trial, a total of 652 patients were randomized into two arms, with the first receiving BRUKINSA (160 mg orally twice daily) and the second receiving ibrutinib (420 mg orally once daily) until disease progression or unacceptable toxicity. The primary analysis of overall response rate (ORR), defined by pre-specified non-inferiority of BRUKINSA versus ibrutinib, was assessed by investigator and independent review committee (IRC) using the modified 2008 iwCLL guidelines, with modification for treatment-related lymphocytosis for patients with CLL, and per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. There was hierarchical testing of non-inferiority followed by superiority in ORR as assessed by investigator and IRC. Key secondary endpoints include progression-free survival (PFS) and event rate of atrial fibrillation or flutter; other secondary endpoints include duration of response, overall survival, and incidence of adverse events. The study is ongoing with a planned formal analysis of PFS when the target number of events is reached.

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA has previously been approved for three indications in the United States: for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (Nov. 2019)*; for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) (Aug. 2021); and for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (Sept. 2021)*.

BRUKINSA is supported by a broad clinical program which includes more than 3,900 subjects in 35 trials across 28 markets. To date, BRUKINSA has received approvals covering 50 countries and regions, including the United States, China, the EU and Great Britain, Canada, Australia, South Korea, Switzerland and additional international markets.

*This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients, most commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 8% of patients. Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse reactions

The most common adverse reactions, including laboratory abnormalities, in ≥ 30% of patients who received BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and musculoskeletal pain (30%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Gamida Cell to Present Corporate Highlights at the JMP Securities Life Sciences Conference

On June 13, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), the leader in the development of NAM-enabled cell therapy candidates for patients with hematologic and solid cancers and other serious diseases, reported that company management will present its corporate highlights at the JMP Securities Life Sciences Conference, June 16, 2022 with a presentation at 2:00 p.m. ET in New York, NY (Press release, Gamida Cell, JUN 13, 2022, View Source [SID1234615943]).

Management will discuss 2022 catalysts and potential milestones including the U.S. market opportunity for omidubicel upon potential U.S. Food and Drug Administration (FDA) approval, accelerating the development of its first-in-class NAM-enabled natural killer (NK) cell therapy candidate, GDA-201, as a potential new approach for patients with follicular and diffuse large B-cell lymphomas, and expansion of its NAM-enabled cell therapy pipeline with multiple next-generation, genetically engineered NK cells.

A webcast of the event will be available on the "Investors & Media" section of Gamida Cell’s website at www.gamida-cell.com, and will be available for at least 14 days following the event.

About Omidubicel

Omidubicel is an advanced cell therapy candidate under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant for patients with blood cancers. Omidubicel is the first stem cell transplant donor source to receive Breakthrough Therapy Designation from the U.S. FDA and has also received Orphan Drug Designation in the U.S. and EU. Gamida Cell has completed an international, multi-center, randomized Phase 3 study (NCT0273029) evaluating the safety and efficacy of omidubicel in patients with hematologic malignancies undergoing allogeneic bone marrow transplant compared to a comparator group of patients who received a standard umbilical cord blood transplant. That study achieved its primary endpoint, demonstrating a highly statistically significant reduction in time to neutrophil engraftment, a key milestone in a patient’s recovery from a stem cell transplant. The Phase 3 study also achieved its secondary endpoints of reduced time to platelet engraftment, reduced infections and fewer days of hospitalization. Gamida Cell initiated a rolling BLA submission for omidubicel in the first quarter of 2022 with full BLA submission on track for the second quarter of 2022. In 2019, approximately 8,000 patients who were 12 years old and up with hematologic malignancies underwent an allogeneic stem cell transplant.1 Unfortunately it is estimated that another 1,200 patients were eligible for transplant but could not find a donor source.2 Omidubicel has the opportunity, upon FDA approval to improve outcomes for patients based on transplanter feedback and increase access for patients to get to transplant. Omidubicel has the potential to treat approximately 2,000 – 2,500 patients each year in the U.S. For more information about omidubicel, please visit View Source

Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

About GDA-201

Gamida Cell applied the capabilities of its nicotinamide (NAM)-enabled cell expansion technology to develop GDA-201, an innate NK cell immunotherapy candidate for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201, the lead candidate in the NAM-enabled NK cell pipeline, has demonstrated promising initial clinical trial results. GDA-201 addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs. Furthermore, GDA-201 improves antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells. There are approximately 40,000 patients with relapsed/refractory lymphoma in the E.U.5 and U.S. which is the patient population that will be studied in the GDA-201 Phase 1/2 clinical trial

For more information about GDA-201, please visit View Source For more information on the Phase 1/2 clinical trial of GDA-201, please visit www.clinicaltrials.gov.

GDA-201 is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

About NAM Technology

Our NAM-enabling technology, supported by positive Phase 3 data, is designed to enhance the number and functionality of targeted cells, enabling us to pursue a curative approach that moves beyond what is possible with existing therapies. Leveraging the unique properties of NAM (Nicotinamide), we can expand and metabolically modulate multiple cell types — including stem cells and natural killer cells — with appropriate growth factors to maintain the cells’ active phenotype and enhance potency. Additionally, our NAM technology improves the metabolic fitness of cells, allowing for continued activity throughout the expansion process.

BeiGene Announces BRUKINSA™ (zanubrutinib) Is Approved in 50 Markets

On June 13, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide reported that its BTK inhibitor BRUKINSA (zanubrutinib) has been approved by the Ministry of Health in Kuwait, the National Health Regulatory Authority in Bahrain and the Ministry of Public Health in Qatar for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy (Press release, BeiGene, JUN 13, 2022, View Source [SID1234615942]). BeiGene is working with NewBridge Pharmaceuticals, a specialty company in the Middle East and North Africa (MENA) regions established to bridge the access gap by partnering with global pharma and biotech companies, to bring BRUKINSA to patients in Kuwait, Bahrain, Qatar, Saudi Arabia, United Arab Emirates, and other markets in the MENA region following regulatory approvals.

"Non-Hodgkin’s lymphoma is among the five most common cancers in Kuwait, Bahrain, and Qatar, with MCL in particular having a poor prognosis. Patients typically require multiple lines of therapy where the duration of response to subsequent lines of treatment is continually reduced," said Dr. Abdul Aziz Hamadah, Head of Hematology Department, Kuwait Cancer Control Center. "BRUKINSA is a next-generation BTK inhibitor designed as a highly potent, selective, bioavailable, and irreversible inhibitor with potentially advantageous pharmacokinetic and pharmacodynamic properties."

"BeiGene’s vision is to develop impactful medicines and reach far more patients around the world. Over the past year, BeiGene has achieved approval for BRUKINSA in five countries in the MENA region including Saudi Arabia, United Arab Emirates, Kuwait, Bahrain and Qatar," said Mohammed Al-Kapany, Senior Director of New Markets in MENA at BeiGene. "We are proud to be on a path to bringing an important new treatment option to patients."

Added Joe Henein, President and CEO of NewBridge Pharmaceuticals, "Continuing our productive collaboration with BeiGene in the MENA region, we look forward to introducing BRUKINSA to physicians and their patients in Kuwait, Bahrain and Qatar."

The recommended dose of BRUKINSA is either 160 mg twice daily or 320 mg once daily, taken orally with or without food. The dose may be adjusted for adverse reactions and reduced for patients with severe hepatic impairment and certain drug interactions.

About Mantle Cell Lymphoma (MCL)

Non-Hodgkin’s lymphoma (NHL) is one of the five most prevalent cancers in Kuwait.i MCL is rare form of NHL, accounting for five percent of all cases. It develops in the outer edge of a lymph node called the mantle zone. Mantle cell lymphoma occurs more often in men than in women. It is usually diagnosed in people in their early 60s.3 MCL has a poor prognosis, with a median survival of three to four years, and is often diagnosed at a later stage of disease.ii

About BRUKINSA

BRUKINSA is supported by a broad clinical program which includes more than 3,900 subjects in 35 trials across 28 markets. To date, BRUKINSA has received more than 20 approvals covering 50 countries and regions, including the United States, China, the EU, and Great Britain, Canada, Australia and additional international markets. Currently, more than 40 additional regulatory submissions are in review around the world.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 16,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU and U.K., Canada, Australia and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, including a biologics license application (BLA) under FDA review, BeiGene and Novartis announced an option, collaboration and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene is promoting five approved Novartis Oncology products across designated regions of China.

Asher Bio Appoints Andrea Pirzkall, M.D., as Chief Medical Officer

On June 13, 2022 Asher Biotherapeutics, Inc. (Asher Bio), a biotechnology company developing precisely-targeted immunotherapies for cancer, autoimmune, and infectious diseases, reported the appointment of Andrea Pirzkall, M.D., as its first Chief Medical Officer (Press release, Asher Biotherapeutics, JUN 13, 2022, View Source [SID1234615941]). Dr. Pirzkall has a multi-disciplinary clinical background and a proven track record in developing cancer therapies from research to commercialization.

"We are delighted to welcome Andrea to the Asher Bio team at this pivotal time as we transition to a clinical-stage company. Her broad background spans early and late-stage development and includes both small molecule and biologic agents. She has expertise in immunotherapies for cancer and is a successful leader of growing clinical teams. Andrea is an ideal fit to our team as we continue to advance our pipeline," said Craig Gibbs, Ph.D., Chief Executive Officer of Asher Bio. "Her expertise and hands-on style will be valuable assets as we implement clinical strategies to deliver our selective and differentiated immunotherapies for patients with cancer and other diseases."

"I am very excited to join Asher Bio’s highly experienced senior management team and to build and lead the clinical development organization to deliver on the company’s promising pipeline of cis-targeted therapeutics," said Dr. Pirzkall. "I am particularly intrigued by the potential of Asher Bio’s cis-targeting platform approach to overcome limitations and broaden the potential of existing immunotherapy by selectively targeting immune cell subsets, and thereby aiming to improve outcomes for patients. That includes Asher Bio’s lead cis-targeted IL-2 immunotherapy, AB248, which is approaching an IND filing and the start of a Phase 1 clinical trial. AB248 has been designed to selectively activate IL-2 signaling in CD8+ effector T cells, while avoiding systemic toxicities and limiting counterproductive pleotropic signaling that results from IL-2 binding to non-targeted cells. I look forward to working with the team to transition this compound into the clinic."

Most recently, Dr. Pirzkall served as Chief Medical Officer at Replimune Group, Inc., where she was responsible for building, developing, and leading clinical development of the company’s pipeline of next-generation oncolytic immunotherapies. Prior to that, Dr. Pirzkall served as Executive Director of Clinical Development at BeiGene, Ltd., where she led and supported the development, startup and execution of several pivotal studies in lung cancer and head and neck cancers, which successfully led to approvals of tislelizumab (anti-PD1) in China and ongoing filings in other jurisdictions. She also served as the global clinical development lead on the BeiGene, Inc./Celgene Corporation joint development committee. Earlier in her career, Dr. Pirzkall spent 10 years at Genentech, Inc., where she held roles of increasing responsibility, including Principal Medical Director and Clinical Development Team Leader. In this role, she worked with cross-functional teams on therapeutics including Avastin, Tarceva, Perjeta, Cotellic and Tecentriq supporting these novel biologic agents through early to late stages of development in oncology as well as through exploratory and combination studies.

Prior to moving to industry, Dr. Pirzkall trained in radiation oncology and completed her dissertation at the University of Heidelberg and the German Cancer Research Center. She completed a fellowship in Medical Physics/Radiation Oncology at the University San Francisco (UCSF) and held academic positions as Associate Adjunct Professor of Radiation Oncology, Radiology, and Neurosurgery at UCSF. Dr. Pirzkall holds a Doctor of Medicine from Friedrich-Schiller University Jena, Germany.

TROPION-Breast02 Phase 3 Trial of Datopotamab Deruxtecan Initiated in Patients with Previously Untreated Metastatic Triple Negative Breast Cancer

On June 13, 2022 Daiichi Sankyo (TSE: 4568) reported that the first patient was dosed in the global TROPION-Breast02 phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus investigator’s choice of chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) not eligible to receive PD-1/PD-L1 inhibitor therapy (Press release, Daiichi Sankyo, JUN 13, 2022, View Source [SID1234615940]).

Datopotamab deruxtecan is a specifically designed TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Approximately 10 to 15% of breast cancers are considered triple negative, the most aggressive subtype of breast cancer.1,2,3 Compared to patients with other breast cancer subtypes, the prognosis for patients with metastatic TNBC is generally worse, with five-year survival rates estimated at 12% and median overall survival generally less than two years.3,4 TNBC is defined by tumors that test negative for estrogen and progesterone hormone receptors (HRs) as well as human epidermal growth factor 2 receptor (HER2), as determined by an IHC test and/or an ISH test; HER2 negative cancers are currently defined as IHC 0, IHC 1+ or IHC 2+/ISH-.3,5

"Patients with metastatic triple negative breast cancer who are not able to receive PD-1/PD-L1 inhibitor treatment often experience recurrence following chemotherapy, so additional options in the first-line treatment setting are needed," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "The TROPION-Breast02 trial will build on the preliminary efficacy and safety profile seen in the relapsed or refractory triple negative breast cancer arm of the TROPION-PanTumor01 trial to evaluate whether datopotamab deruxtecan may be a more effective treatment than chemotherapy for patients in the first line setting."

"Initial results of datopotamab deruxtecan in patients with pretreated metastatic triple negative breast cancer, a group with a significant unmet need, have been encouraging," said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. "We are building on these early results by moving forward with the TROPION-Breast02 trial, the second pivotal trial of datopotamab deruxtecan in breast cancer, to determine if this antibody drug conjugate may potentially be used earlier in the treatment of metastatic triple negative breast cancer."

About TROPION-Breast02
TROPION-Breast02 is a global, randomized, open-label, two-arm, multicenter study assessing the efficacy and safety of datopotamab deruxtecan (6 mg/kg) compared with investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC. TNBC is defined as HR negative, meaning tumors test negative for estrogen and progesterone hormone receptors, and HER2 negative, determined by an IHC test and/or an ISH test.3,5 HER2 negative cancers are currently defined as IHC 0, IHC 1+ or IHC 2+/ISH-.5 Patients must not be candidates for PD-1/PD-L1 inhibitor therapy and must be eligible for one of the investigator’s choice of chemotherapy options.

The dual primary endpoints of TROPION-Breast02 are progression-free survival (PFS) assessed by blinded independent central review and overall survival. Secondary endpoints include PFS assessed by investigator, objective response rate, duration of response, disease control rate, pharmacokinetics and safety.

TROPION-Breast02 will randomize approximately 600 patients with TNBC at sites in Asia, Africa, Europe and North America. For more information visit ClinicalTrials.gov.

About Triple Negative Breast Cancer
Approximately 10 to 15% of breast cancers are considered triple negative, the most aggressive subtype of breast cancer.1,2,3 Compared to patients with other breast cancer subtypes, the prognosis for patients with metastatic TNBC is generally worse, with five-year survival rates estimated at 12% and median overall survival generally less than two years.3,4 TNBC is defined by tumors that test negative for estrogen and progesterone hormone receptors (HRs) as well as human epidermal growth factor 2 receptor (HER2), as determined by an IHC test and/or an ISH test; HER2 negative cancers are currently defined as IHC 0, IHC 1+ or IHC 2+/ISH-.3,5

About TROP2
TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein overexpressed in several types of solid tumors, including breast cancer.6 TROP2 expression has been detected in a wide range of breast cancer subtypes, including approximately 80% of patients with TNBC.7,8,9 High TROP2 expression is an unfavorable prognostic factor for overall survival in all types of breast cancer.7

About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of three leading ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG13 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers.

A comprehensive development program called TROPION is underway globally with trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple solid tumors, including TNBC, HR positive/HER2 negative breast cancer, non-small cell lung cancer, small cell lung cancer, urothelial, gastric and esophageal cancer. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialize datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of datopotamab deruxtecan.