Goserelin Acetate

First and only next-generation oral SERD and complete ER antagonist to demonstrate 1st-line benefit in combination with widely approved CDK4/6 inhibitors LONDON, UK I February 26, 2025 I Positive high-level results from a planned interim analysis of the SERENA-6 Phase III trial showed that AstraZeneca’s camizestrant in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) demonstrated a highly statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS). The trial evaluated switching to the camizestrant combination versus continuing standard-of-care treatment with an aromatase inhibitor (AI) (anastrozole or letrozole) in combination with a CDK4/6 inhibitor in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumours have an emergent ESR1 mutation. The key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of this interim analysis. However, the camizestrant combination demonstrated a trend toward improvement in PFS2. The trial will continue as planned to further assess key secondary endpoints. SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumour DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The novel trial design used ctDNA monitoring at the time of routine tumour scan visits to identify patients for early signs of endocrine resistance and the emergence of ESR1 mutations. Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to camizestrant from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor. François-Clément Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie & UVSQ/Université Paris-Saclay, France, and co-principal investigator for the trial, said: “Patients have an urgent need for new treatments that delay disease progression on 1st-line endocrine-based therapies. The results from SERENA-6 show that switching from an aromatase inhibitor to camizestrant in combination with any of the three CDK4/6 inhibitors after emergence of an ESR1 mutation delays progression of disease and extends the benefit of 1st-line treatment, representing an important step forward for patients, and a potential shift in clinical practice.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “These impressive results demonstrate the versatility of camizestrant in combination with all the widely approved CDK4/6 inhibitors to provide a well-tolerated new potential treatment option in the first-line setting for the one in three patients with HR-positive, HER2-negative advanced breast cancer whose tumours develop ESR1 mutations during treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor. This critical read-out moves us one step closer to realising the potential of camizestrant to become a new standard-of-care as we look to shift the treatment paradigm and establish this new endocrine therapy backbone in HR-positive breast cancer.” The safety profile of camizestrant in combination with palbociclib, ribociclib or abemaciclib in SERENA-6 was consistent with the known safety profile of each medicine. No new safety concerns were identified and discontinuations were very low and similar in both arms. Globally, approximately 200,000 patients with HR-positive breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies that target estrogen receptor (ER)-driven disease, which are often paired with CDK4/6 inhibitors. 1-3 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease. 3 Mutations in the ESR1 gene are a key driver of endocrine resistance and are widely tested for in clinical practice. 4,5 Thesemutations develop during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes. 4,5 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment without disease progression. 1 Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 6 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally. 6 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 7 HR-positive breast cancer, characterised by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumours considered HR-positive and HER2-negative. 7 ERs often drive the growth of HR-positive breast cancer cells. 8 Once resistance to the treatment of HR-positive breast cancer with CDK4/6 inhibitors and current endocrine therapies occurs, treatment options are limited and survival rates are low with 35% of patients anticipated to live beyond five years after diagnosis. 3,7,9 The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research. SERENA-6 SERENA-6 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib ) versus treatment with an AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) in patients with HR-positive, HER2-negative advanced breast cancer (patients with either locally advanced disease, or metastatic disease) whose tumours have an emergent ESR1 mutation. The global trial enrolled 315 adult patients with histologically confirmed HR-positive, HER2-negative advanced breast cancer, undergoing treatment with an AI in combination with a CDK4/6 inhibitor as 1st-line treatment. The primary endpoint of the SERENA-6 trial is PFS as assessed by investigator, with secondary endpoints including OS, and PFS2 by investigator assessment. Camizestrant Camizestrant is an investigational, potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist that is currently in Phase III trials for the treatment of HR-positive breast cancer. AstraZeneca’s broad, robust and innovative clinical development programme, including the SERENA-6, SERENA-4, CAMBRIA-1 and CAMBRIA-2 trials, is evaluating the safety and efficacy of camizestrant when used as a monotherapy or in combination with other agents to address a number of areas of unmet need in this specific type of breast cancer. Camizestrant has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations. In the SERENA-2 Phase II trial, camizestrant demonstrated PFS benefit versus Faslodex (fulvestrant) irrespective of ESR1 mutation status or prior treatment with CDK4/6 inhibitors in patients with ER-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy. The SERENA-1 Phase I trial demonstrated that camizestrant is well tolerated and has a promising anti-tumour profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors. Combinations with other agents are ongoing in SERENA-1. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, 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. With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP-2-directed ADC, Datroway (datopotamab deruxtecan) and next-generation oral SERD and potential new medicine camizestrant. PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and 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 these settings and to explore its potential in earlier disease. AstraZeneca is also exploring the efficacy and safety of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab). 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. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @ AstraZeneca . Contacts For details on how to contact the Investor Relations Team, please click here . For Media contacts, click here . References SOURCE: AstraZeneca

Based on DESTINY-Breast06 Phase III trial results which showed ENHERTU demonstrated superiority vs. chemotherapy with a median progression-free survival of more than one year Approval brings AstraZeneca and Daiichi Sankyo’s ENHERTU to an earlier HR-positive treatment setting and broadens the patient population eligible for treatment with a HER2-directed therapy to those with HER2-ultralow disease WILMINGTON, DE, USA I January 27, 2025 I AstraZeneca and Daiichi Sankyo’sENHERTU ® (fam-trastuzumab deruxtecan-nxki) has been approved in the US for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a Food and Drug Administration (FDA)-approved test, that has progressed on one or more endocrine therapies in the metastatic setting. The approval was granted by the FDA after securing Priority Review and Breakthrough Therapy Designation and was based on results from the DESTINY-Breast06 Phase III trial, which were presented at the 2024 American Society of Clinical Oncology (ASCO) Meeting and published in The New England Journal of Medicine . Aditya Bardia, MD, MPH, Program Director of Breast Oncology and Director of Translational Research Integration, UCLA Health Jonsson Comprehensive Cancer Center, US, and investigator in the DESTINY-Breast06 trial, said: “Endocrine therapy is typically used in the initial treatment of HR-positive metastatic breast cancer and following progression, subsequent chemotherapy is associated with poor outcomes. With a median progression-free survival exceeding one year and a response rate of more than 60 percent, trastuzumab deruxtecanoffers a potential new standard of care for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer following endocrine therapy.” Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca, said: “Building on the practice-changing previous approvals for ENHERTU, this new approval brings this important medicine to an earlier treatment setting and a broader patient population with HER2-expressing metastatic breast cancer. The approval also highlights the importance of testing metastatic breast cancer tumors for detectable staining with astandard IHC test to identify those who may be eligible for treatment with ENHERTU following endocrine therapy.” Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, said: “ENHERTUcontinues to redefine the classification and treatment of HR-positive metastatic breast cancer with important new data across the spectrum of HER2 expression. Today’s approval underscores our ongoing commitment to realizing the full potential of this innovative antibody drug conjugate and represents another paradigm shift in how certain breast cancers can be treated.” Krissa Smith, Vice President, Education, Susan G. Komen, said: “We are excited to see more treatment options for these patients which enable more personalized care. It is critical for patients to understand the HER2 status of their metastatic breast cancer to help them make informed treatment decisions. Patients with tumors that are HER2-low or HER2-ultralow now have more options to consider with their healthcare team.” In the trial, ENHERTU showed a 36% reduction in the risk of disease progression or death versus chemotherapy (hazard ratio [HR] 0.64; 95% confidence interval [CI]: 0.54-0.76; p<0.0001) in the overall trial population of patients with chemotherapy-naïve HER2-low or HER2-ultralow metastatic breast cancer. A median progression-free survival (PFS) of 13.2 months was seen in patients randomized to ENHERTUcompared to 8.1 months in those randomized to chemotherapy. The confirmed objective response rate (ORR) in the overall trial population was 62.6% for ENHERTUversus 34.4% for chemotherapy. In an exploratory analysis of patients with HER2-ultralow expression, results were seen to be consistent between patients with HER2-low expression and HER2-ultralow expression. HER2 status in the trial was confirmed by a central laboratory and was performed on a tumor sample obtained at the time of initial metastatic diagnosis or later. Approximately 85-90% of patients with HR-positive, HER2-negative metastatic breast cancer were determined to have actionable levels of HER2-expression. 1 Further, nearly two-thirds of patients previously assessed as IHC 0 at a local laboratory were classified as HER2-low or HER2-ultralow upon central analysis of the tumor sample. 1 The safety profile of ENHERTU in DESTINY-Breast06 was consistent with previous clinical trials of ENHERTUin breast cancer with no new safety concerns identified. ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. ENHERTUis already approved in more than 75 countries, including the US, for patients with HER2-low metastatic breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. Regulatory applications are under review in the EU, Japan and several other countries based on the DESTINY-Breast06 results. Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide . Notes Financial considerations Following this approval for ENHERTUin the US, an amount of $175m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the HER2-low and HER2-ultralow chemotherapy-naïve breast cancer indication. The milestone will be capitalized as an addition to the upfront payment made by AstraZeneca to Daiichi Sankyo in 2019 and subsequent capitalized milestones and will be amortized through the profit and loss statement. Sales of ENHERTU in the US are recognized by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from ENHERTU sales in the US as Alliance Revenue in the Company’s financial statements. Further details on the financial arrangements were set out in the March 2019 announcement of the collaboration. Breast cancer and HER2 expression Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 2 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally. 2 In the US, more than 300,000 cases of breast cancer are diagnosed annually. 3 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 4 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer. 5 Patients with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are classified as HER2-positive and treated with HER2-directed therapies, representing approximately 15-20% of all breast cancers. 6 Historically, tumors that were not classified as HER2-positive were classified as HER2-negative. 7 HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers. 4 Endocrine therapies are widely given consecutively in the early lines of treatment for HR-positive metastatic breast cancer. However, after initial treatment, further efficacy from endocrine therapy is often limited. 8 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 8-11 Despite being classified as HER2-negative, many of these tumors may still carry some level of HER2 expression. 7 Prior to the approvals of ENHERTU in HER2-low or HER2-ultralow metastatic breast cancer based on the DESTINY-Breast04 and DESTINY-Breast06 trials, there were no targeted therapies specifically approved for these patient populations. 12,13 DESTINY-Breast06 DESTINY-Breast06 is a global, randomized, open-label, Phase III trial evaluating the efficacy and safety ofENHERTU (5.4mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients were also eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting 1st-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months. The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), overall survival (OS) in the HER2-low patient population and OS in the overall trial population. Other secondary endpoints include ORR, duration of response, time to first subsequent treatment or death, time to second subsequent treatment or death and safety. DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) in Asia, Europe, Australia, North America and South America. For more information about the trial, visit ClinicalTrials.gov . ENHERTU ENHERTU is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTUis the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. ENHERTU (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridization [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU(5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. ENHERTU (5.4 mg/kg) is approved in the US for adult patients with unresectable or metastatic hormone receptor HR-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic settingbased on the results from the DESTINY-Breast06 trial. ENHERTU (5.4mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 ( ERBB2 ) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 , DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication will depend on whether a randomized controlled confirmatory clinical trial can demonstrate clinical benefit in this population. ENHERTU (5.4mg/kg) is approved in the US, Russia, Israel and Brazil for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02 , DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU development program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan-dlnk in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan-dlnk. 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 tumor environment. With ENHERTU, a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicinesfulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan-dlnk, in this setting. PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with Merck & Co., Inc. (MSD outside the US and Canada) continue to research olaparib in these settings and to explore its potential in earlier disease. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan-dlnk alone and in combination with immunotherapydurvalumab, capivasertib in combination with chemotherapy, and durvalumab in combination with other oncology medicines, including olaparib and ENHERTU. 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 catalyze 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. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References SOURCE: AstraZeneca