Positive high-level results from the SERENA-2 Phase II trial showed that AstraZeneca’s next-generation oral selective estrogen receptor degrader (ngSERD) camizestrant met the primary endpoint of demonstrating a statistically significant and clinically meaningful progression-free survival (PFS) benefit at both 75mg and 150mg dose levels versus Faslodex (fulvestrant) 500mg in post-menopausal patients with estrogen receptor (ER)-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy for advanced disease.
Camizestrant was well tolerated, and its safety profile was consistent with that observed in previous trials with no new safety signals identified.
Breast cancer is the most common cancer worldwide, with an estimated 2.3 million patients diagnosed in 2020.1 Approximately 70% of breast cancer tumours are considered HR-positive and HER2-low or negative.2 Endocrine therapies are widely used for the treatment of HR-positive breast cancer, but many patients with advanced disease develop resistance to 1st-line CDK4/6 inhibitors and estrogen receptor-targeting therapies, underscoring the need for additional options.3
Mafalda Oliveira, MD, PhD, Vall d’Hebron Institute of Oncology in Barcelona, Spain and lead investigator in the SERENA-2 Phase II trial, said: “The results from SERENA-2 show that camizestrant provides a significant improvement in progression-free survival compared to fulvestrant, which has been used to treat patients with HR-positive breast cancer for almost twenty years. These results are meaningful, highlighting the potential of this next-generation oral SERD and supporting the ongoing research program.”
Susan Galbraith, EVP, Oncology R&D, AstraZeneca, said: “Our goal with our next generation oral SERD camizestrant is to improve on currently available endocrine therapies for patients with HR-positive breast cancer in early and metastatic disease. The exciting efficacy and compelling safety results from the SERENA-2 trial underscore the potential for camizestrant to achieve this goal in patients with ER-driven breast cancer and we look forward to advancing our comprehensive Phase III clinical programme for camizestrant.”
The data will be presented at a forthcoming medical meeting.
AstraZeneca has a broad clinical development programme for camizestrant in advanced breast cancer, including the pivotal SERENA-6 Phase III trial assessing camizestrant in
combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib or abemaciclib) in patients with HR-positive metastatic breast cancer who have detectable ESR1 mutations on 1st-line treatment and the SERENA-4 Phase III trial evaluating camizestrant plus palbociclib in HR-positive, locally advanced or metastatic breast cancer from the start of therapy in the 1st-line setting. The indication for SERENA-6 has been granted Fast Track Designation by the US Food and Drug Administration.
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in development for patients with breast cancer. In addition to these results, the Company has also announced today positive results from the CAPitello-291 Phase III trial of capivasertib in HR-positive advanced breast cancer.
Notes
HR-positive breast cancer
HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer, and the growth of HR-positive breast cancer cells is often driven by ER.2,4,5 Endocrine therapies that target ER-driven disease are widely used as 1st-line treatment for this form of breast cancer in the advanced setting, and often paired with CDK4/6 inhibitors.3 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease and treatment options are limited.3 Optimising endocrine therapy and overcoming resistance for patients with ER-driven disease at all stages of treatment are active areas of focus for breast cancer research.
SERENA-2
SERENA-2 is a randomised, open-label, parallel group, multicentre Phase II trial evaluating camizestrant at several dose levels compared to Faslodex in advanced ER-positive, HER2-negative breast cancer. The primary endpoints are PFS defined by response evaluation criteria in solid tumours (RECIST) version 1.1 for 75mg camizestrant versus Faslodex (500mg) and for 150mg camizestrant versus Faslodex. 240 patients were randomised to receive camizestrant or Faslodex until disease progression. Secondary endpoints include safety, objective response rate and clinical benefit rate (CBR) at 24 weeks.
SERENA-2 is part of a larger clinical programme focused on camizestrant, evaluating the safety and efficacy when used as a monotherapy or in combination with other agents, to address a number of areas of unmet need in HR-positive breast cancer.
Camizestrant
Camizestrant is a potent, next-generation oral SERD and pure ERα antagonist, that has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations.
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, a CDK4/6 inhibitor. Combinations with other agents are ongoing in SERENA-1.
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.
With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca is aiming to improve outcomes in previously treated HER2-positive and HER2-low breast cancer. AstraZeneca and Daiichi Sankyo 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 (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with ngSERD and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
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 metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.
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 capivasertib in combination with chemotherapy, and 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.
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 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
