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Business Wire
a day ago
- Business
- Business Wire
BeOne Medicines Unveils Promising Clinical Data for Two Novel Breast Cancer Therapies at ASCO 2025
SAN CARLOS, Calif.--(BUSINESS WIRE)-- BeOne Medicines Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company, announced new clinical data from its emerging breast cancer pipeline at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Poster presentations feature preliminary results of the dose escalation studies of two investigational molecules: BG-C9074, a novel B7-H4-targeting antibody-drug conjugate (ADC) in patients with advanced solid tumors, including breast cancer, and BG-68501, a cyclin-dependent kinase-2 inhibitor (CDK2i), in HR+/HER2- breast cancer patients with prior CDK4/6i exposure. 'Presenting the first clinical data for two novel breast cancer candidates at ASCO 2025 marks a pivotal moment for BeOne,' said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne. 'These early results highlight the strong potential of our B7-H4-targeting ADC and CDK2 inhibitor to address critical gaps in breast cancer treatment. Alongside our advancing CDK4 inhibitor, they represent just the beginning of a pipeline built on targeted, biology-driven innovation. As we debut our new identity as BeOne, this milestone reflects the momentum behind our science and our commitment to delivering impactful therapies to cancer patients worldwide.' BeOne is advancing a robust pipeline of differentiated investigational medicines for breast cancer that may both effectively combat the disease and potentially improve quality of life for patients receiving treatment. BG-C9074, a B7-H4-targeting ADC (Abstract #3033) BeOne presented initial results of the ongoing first-in-human, Phase 1a dose escalation study of BG-C9074 monotherapy in 78 patients with advanced solid tumors, of which more than a quarter were breast cancer patients. BG-C9074, an investigational topoisomerase I inhibitor ADC that targets the B7-H4 protein, which is broadly expressed in breast and gynecologic cancers, is designed with an innovative drug linker to deliver a potent cancer-killing drug directly to the cancer cells. With limited follow-up among the 56 efficacy-evaluable patients, preliminary clinical responses were observed at multiple dose levels across various tumor types without selection for B7-H4 expression in these heavily pretreated patients. Confirmed overall response rate (ORR) was 16.1% (9/56; 95% CI: 7.6%–28.3%), with 9 confirmed partial responses; unconfirmed ORR was 25.0% (14/56; 14.4%-38.4%) (n=14 partial responses). Confirmed disease control rate (DCR) was 73.2% (59.7%-84.2%) and confirmed clinical benefit rate (CBR) was 17.9% (8.9%-30.4%). Pharmacokinetics (PK) were observed to be approximately dose-proportional across dose levels. BG-C9074 showed a manageable safety and tolerability profile in patients with B7-H4 advanced solid tumors, including breast cancer. There were 5 dose-limiting toxicities (DLTs) reported among 3 dose levels, all related to treatment: grade 3 fatigue (n=1); grade 3 febrile neutropenia (n=2); and grade 4 platelet count decreased (n=2). The most common treatment-emergent adverse events (TEAEs) were nausea, fatigue, and neutropenia*. The most common grade ≥3 TEAEs were neutropenia and thrombocytopenia†. There were no TEAEs leading to treatment discontinuation or death. These data support the continued development of BG-C9074 in patients with advanced solid tumors. (NCT06233942) BG-68501, a CDK2 inhibitor (Abstract# 3115) Dose-escalation data from the first-in-human, Phase 1a study of a novel CDK2 inhibitor, BG-68501, were presented as a poster today. BG-68501 is designed to address elevated CDK2 activity as well as cyclin E1-driven upregulation, two key resistance mechanisms that often limit the effectiveness of CDK4/6 inhibitors in treating HR+/HER2- breast cancer. CDK inhibitors target checkpoint proteins that control cell division to stop the growth of cancer cells. A total of 57 enrolled patients with advanced solid tumors, including 19 patients with HR+/HER2- metastatic breast cancer, received BG-68501 as monotherapy or in combination with fulvestrant in escalating dose cohorts (all received prior CDK4/6i). Of the 37 efficacy-evaluable patients (all with monotherapy), unconfirmed overall response rate (ORR) was 5.4% (2/37; 95% CI: 0.7%–18.2%). Two extensively pretreated patients (5.4%) experienced unconfirmed partial response (PR), 15 patients (40.5%) had stable disease (SD), 15 patients (40.5%) had progressive disease (PD), and 5 patients (13.5%) were not evaluable/not assessed. Of the 2 patients with PR, both were breast cancer patients, and one was ongoing with treatment at the time of data cutoff, while the other had discontinued treatment. Unconfirmed clinical benefit rate (CBR) was 8.1% (3/37; 95% CI: 1.7%-21.9%) and unconfirmed disease control rate (DCR) was 45.9% (17/37; 95% CI: 29.5%-63.1%). BG-68501 demonstrated a linear PK profile consistent with preclinical data and signs of pharmacodynamic responses. BG-68501 demonstrated a manageable safety and tolerability profile, with no DLTs observed to date during dose escalation. The most common TEAEs were vomiting, nausea, and fatigue, and TEAEs leading to treatment discontinuation occurred in 4 patients (7%) across all dose levels. There were no TEAEs leading to death. The data support continued development of BG-68501 as a next-line option for tumors with CDK2 dependency. (NCT06257264) For additional information about our presence at the 2025 ASCO Annual Meeting, please visit our meeting hub: BeOne will host an investor R&D Day on June 26 at 8:30 am ET covering its deep and broad global innovation pipeline and platforms, as well as the Company's vision, differentiated capabilities, and value creation drivers. A live webcast will be accessible from the investors section of BeOne's website at or An archived replay will be available for 90 days following the event. About Our Breast Cancer Pipeline BeOne is advancing a robust portfolio of investigational medicines for breast cancer, including three molecules in clinical development – two cyclin-dependent kinase (CDK) inhibitors, BGB-43395, a CDK4 inhibitor, and BG-68501, a CDK2 inhibitor, and an antibody-drug conjugate (ADC), BG-C9074. BeOne also plans to evaluate the potential of BCL2 inhibition in breast cancer, with next-generation BCL2 inhibitor, BGB-21447, expected to begin clinical testing in solid tumor indications soon. Multispecific antibodies and targeted protein degraders with potential applications in breast cancer are among the preclinical assets being developed. About Breast Cancer Breast cancer accounts for close to one in four cancer cases and one in six cancer deaths in women worldwide. 1 Globally, breast cancer is the second most common cancer and the fourth highest cause of cancer mortality as well as the leading cause of cancer death in women. 1 More than 2.3 million patients were diagnosed with breast cancer in 2022, and over 666,000 deaths were reported globally. 1 Approximately two-thirds of breast cancer cases are the HR+/HER2- subtype. 2 About BeOne BeOne Medicines is a global oncology company domiciled in Switzerland that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a portfolio spanning hematology and solid tumors, BeOne is expediting development of its diverse pipeline of novel therapeutics through its internal capabilities and collaborations. With a growing global team of more than 11,000 colleagues spanning six continents, the Company is committed to radically improving access to medicines for far more patients who need them. To learn more about BeOne, please visit and follow us on LinkedIn, X, Facebook and Instagram. Forward-Looking Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the potential of BeOne's B7-H4-targeting ADC and CDK2 inhibitor to address critical gaps in breast cancer treatment; the ability of BeOne to deliver impactful therapies to cancer patients worldwide; the ability of BeOne's pipeline to effectively combat breast cancer and improve quality of life for patients; and BeOne's plans, commitments, aspirations, and goals under the heading 'About BeOne.' Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeOne's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeOne's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeOne's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeOne's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeOne's limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and maintain profitability; and those risks more fully discussed in the section entitled 'Risk Factors' in BeOne's most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeOne's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeOne undertakes no duty to update such information unless required by law. To access BeOne media resources, please visit our News & Media site. *Neutropenia was defined by a custom MedDRA basket with neutropenia and neutrophil count decrease preferred terms. †Thrombocytopenia was defined by a custom MedDRA basket with thrombocytopenia and platelet count decreased preferred terms. 1 Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. April 4, 2024. 2 National Cancer Institute, SEER. Cancer Stat Facts: Female Breast Cancer Subtypes. Accessed November 11, 2024.
Yahoo
2 days ago
- Business
- Yahoo
Camizestrant reduced the risk of disease progression or death by 56% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 Phase III trial
First pivotal trial to demonstrate clinical value of monitoring circulating tumor DNA to detect and treat emerging resistance in 1st-line therapy ahead of disease progression in breast cancer First and only next-generation oral SERD and complete ER antagonist to demonstrate consistent progression-free survival benefit in combination with widely approved CDK4/6 inhibitors in 1st-line advanced breast cancer WILMINGTON, Del., June 01, 2025--(BUSINESS WIRE)--Positive results from 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 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 tumors have an emergent ESR1 mutation. These results will be presented today during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL (abstract #LBA4) and simultaneously published in The New England Journal of Medicine. Results showed the camizestrant combination reduced the risk of disease progression or death by 56% compared to standard-of-care treatment (based on a hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.31–0.60; p<0.00001) as assessed by investigator. Median PFS was 16.0 months for patients who switched to the camizestrant combination versus 9.2 months for the comparator arm. Importantly, a consistent PFS benefit was observed across all CDK4/6 inhibitors and clinically relevant subgroups in the trial, including analysis by age, race, region, time of ESR1 mutation detection and type of ESR1 mutation. The camizestrant combination was also associated with a meaningful delay in time to deterioration in quality of life, where in an exploratory endpoint, the camizestrant combination reduced the risk of deterioration in global health status and quality of life by 47% compared with the AI combination (HR 0.53; 95% CI, 0.33-0.82; nominal p<0.001). The median time to deterioration of global health status was 23.0 months in patients treated with the camizestrant combination, versus 6.4 months in patients that continued treatment with the AI combination (EORTC QLQ-C30). The camizestrant combination also delayed the time to deterioration of pain compared with the AI combination. Data for 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, a trend toward extended treatment benefit was observed with the camizestrant combination based on PFS2 (HR 0.52; 95% CI 0.33-0.81; p=0.0038 [interim analysis threshold p=0.0001]). The trial will continue to assess OS, PFS2 and other key secondary endpoints. Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, London, UK, and co-principal investigator for the trial, said: "Today's news marks a pivotal moment in breast cancer care and redefines how we think about drug resistance in this type of breast cancer. The results of the innovative SERENA-6 trial 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 more than halved the risk of disease progression or death and delayed deterioration in quality of life by nearly 18 months. This proactive approach exemplifies a new treatment strategy in oncology; by treating developing resistance before it causes disease progression and deterioration in quality of life, we can extend the benefit of 1st-line treatment to optimize patient outcomes." Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumor DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer. Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this 1st-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of HR-positive breast cancer." Summary of results: SERENA-6 Camizestrant + CDK4/6 inhibitor (n=155) AI + CDK4/6 inhibitor (n=155) PFSi Median PFS (months) 16.0 (12.7-18.2) 9.2 (7.2-9.5) Hazard ratio (95% CI) 0.44 (0.31-0.60) p-value p<0.00001 Time to deterioration in global health status/quality of lifeii Mean TTD (months) 23.0 (13.8-NC) 6.4 (2.8, 14.0) Hazard ratio (95% CI) 0.53 (0.33-0.82) p-value (nominal) p<0.001 PFS2iii Events 38 47 Hazard ratio (95% CI) 0.52 (0.33-0.81) p-value P=0.0038 [interim analysis threshold P=0.0001] CI, confidence interval; HR, hazard ratio; NC, not calculable; TTD, time-to-deterioration.i PFS was defined per RECIST v1.1. HR was estimated using the Cox proportional hazard model adjusted for stratification Assessments were conducted at baseline, weeks 4, 8 and 12 and then every 8 weeks until PFS2. Analysis conducted in patients with a baseline score and at least one post-baseline assessment. TTD in global health status/quality of life, an exploratory endpoint, was defined as the time from randomization to first deterioration that was confirmed at a subsequent timepoint measured using the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire (EORTC QLQ-30). Deterioration was defined as a decrease from baseline ≥16.6. HR was estimated using the Cox proportional hazard model stratified by time of ESR1 mutation detection (one test vs more than one test), and time from initiation of AI + CDK4/6i to randomization (<18 months vs. ≥18 months).iii HR was estimated using the Cox proportional hazard model adjusted for stratification factors. Final PFS2 analysis will occur at 158 PFS2 events. 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. Consistent with the longer duration of exposure to the combination of camizestrant and CDK4/6 inhibitors in the trial, Grade 3 or higher adverse events from all causes occurred in 60% of patients in the camizestrant arm versus 46% in the AI arm; the majority of which were hematological events typically associated with CDK4/6 inhibitor treatment and included neutropenia (45% vs. 34%), anemia (5% vs. 5%) and leukopenia (10% vs. 3%). If experienced, photopsia - reported as brief flashes of light in the peripheral vision - did not impact daily activities of patients in the trial and was reversible. There were no structural changes in the eye or changes in visual acuity. No new safety signals were identified and discontinuation rates were very low and similar in both arms, with 1% patients discontinuing camizestrant and 2% patients discontinuing an AI. Discontinuation of the CDK4/6 inhibitor occurred in 1% of patients in both arms of the trial. SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumor 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 tumor scans 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. Based on the results of the SERENA-6 Phase III trial, camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) has been granted Breakthrough Therapy Designation (BTD) in the US by the Food and Drug Administration for the treatment of adult patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer upon emergence of ESR1 mutation during first-line endocrine-based therapy. Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.1 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.2 HR-positive breast cancer, characterized by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumors considered HR-positive and HER2-negative.2 ERs often drive the growth of HR-positive breast cancer cells.3 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.4-6 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.6 Once this occurs, treatment options are limited and survival rates are low with 35% of patients anticipated to live beyond five years after diagnosis.2,6,7 Mutations in the ESR1 gene are a key driver of endocrine resistance and are widely tested for in clinical practice at time of disease progression on 1st-line therapies.8,9 These mutations emerge during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes.8,9 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment without disease progression.4 The optimization 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, randomized 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 tumors 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 program, 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 CDK4/6 inhibitors to address a number of areas of unmet need in HR-positive, HER2-negative 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 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-tumor profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors. 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 tumor environment. With fam-trastuzumab deruxtecan-nxki, 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 fulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, the TROP-2-directed ADC, datopotamab deruxtecan-dlnk and next-generation oral SERD and potential new medicine camizestrant. 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. AstraZeneca is also exploring the potential 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 datopotamab deruxtecan-dlnk alone and in combination with immunotherapy 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 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's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit and follow the Company on social media @AstraZeneca. References Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. doi: 10.3322/caac.21834. National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: Accessed June 2025. Scabia V, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun. 2022; 10.1038/s41467-022-30898-0. Cerner CancerMPact database. Accessed June 2025. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944. Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5):821-30. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available at: Accessed June 2025. Brett O, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor‑positive breast cancer. Breast Cancer Res. 2021; 23:85. Zundelevich, A, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020; 22:16. US-101612Last updated 06/25 View source version on Contacts Media Inquiries Fiona Cookson +1 212 814 3923Jillian Gonzales +1 302 885 2677 US Media Mailbox: usmediateam@
Business Wire
2 days ago
- Health
- Business Wire
Camizestrant reduced the risk of disease progression or death by 56% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 Phase III trial
WILMINGTON, Del.--(BUSINESS WIRE)--Positive results from 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 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 tumors have an emergent ESR1 mutation. These results will be presented today during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL (abstract #LBA4) and simultaneously published in The New England Journal of Medicine. Results showed the camizestrant combination reduced the risk of disease progression or death by 56% compared to standard-of-care treatment (based on a hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.31–0.60; p<0.00001) as assessed by investigator. Median PFS was 16.0 months for patients who switched to the camizestrant combination versus 9.2 months for the comparator arm. Importantly, a consistent PFS benefit was observed across all CDK4/6 inhibitors and clinically relevant subgroups in the trial, including analysis by age, race, region, time of ESR1 mutation detection and type of ESR1 mutation. The camizestrant combination was also associated with a meaningful delay in time to deterioration in quality of life, where in an exploratory endpoint, the camizestrant combination reduced the risk of deterioration in global health status and quality of life by 47% compared with the AI combination (HR 0.53; 95% CI, 0.33-0.82; nominal p<0.001). The median time to deterioration of global health status was 23.0 months in patients treated with the camizestrant combination, versus 6.4 months in patients that continued treatment with the AI combination (EORTC QLQ-C30). The camizestrant combination also delayed the time to deterioration of pain compared with the AI combination. Data for 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, a trend toward extended treatment benefit was observed with the camizestrant combination based on PFS2 (HR 0.52; 95% CI 0.33-0.81; p=0.0038 [interim analysis threshold p=0.0001]). The trial will continue to assess OS, PFS2 and other key secondary endpoints. Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, London, UK, and co-principal investigator for the trial, said: 'Today's news marks a pivotal moment in breast cancer care and redefines how we think about drug resistance in this type of breast cancer. The results of the innovative SERENA-6 trial 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 more than halved the risk of disease progression or death and delayed deterioration in quality of life by nearly 18 months. This proactive approach exemplifies a new treatment strategy in oncology; by treating developing resistance before it causes disease progression and deterioration in quality of life, we can extend the benefit of 1st-line treatment to optimize patient outcomes.' Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: 'As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumor DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer. Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this 1st-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of 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. Consistent with the longer duration of exposure to the combination of camizestrant and CDK4/6 inhibitors in the trial, Grade 3 or higher adverse events from all causes occurred in 60% of patients in the camizestrant arm versus 46% in the AI arm; the majority of which were hematological events typically associated with CDK4/6 inhibitor treatment and included neutropenia (45% vs. 34%), anemia (5% vs. 5%) and leukopenia (10% vs. 3%). If experienced, photopsia - reported as brief flashes of light in the peripheral vision - did not impact daily activities of patients in the trial and was reversible. There were no structural changes in the eye or changes in visual acuity. No new safety signals were identified and discontinuation rates were very low and similar in both arms, with 1% patients discontinuing camizestrant and 2% patients discontinuing an AI. Discontinuation of the CDK4/6 inhibitor occurred in 1% of patients in both arms of the trial. SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumor 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 tumor scans 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. Based on the results of the SERENA-6 Phase III trial, camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) has been granted Breakthrough Therapy Designation (BTD) in the US by the Food and Drug Administration for the treatment of adult patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer upon emergence of ESR1 mutation during first-line endocrine-based therapy. Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 1 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally. 1 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. 2 HR-positive breast cancer, characterized by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumors considered HR-positive and HER2-negative. 2 ERs often drive the growth of HR-positive breast cancer cells. 3 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. 4-6 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease. 6 Once this occurs, treatment options are limited and survival rates are low with 35% of patients anticipated to live beyond five years after diagnosis. 2,6,7 Mutations in the ESR1 gene are a key driver of endocrine resistance and are widely tested for in clinical practice at time of disease progression on 1st-line therapies. 8,9 These mutations emerge during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes. 8,9 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment without disease progression. 4 The optimization 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, randomized 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 tumors 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 program, 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 CDK4/6 inhibitors to address a number of areas of unmet need in HR-positive, HER2-negative 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 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-tumor profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors. 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 tumor environment. With fam-trastuzumab deruxtecan-nxki, 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 fulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, the TROP-2-directed ADC, datopotamab deruxtecan-dlnk and next-generation oral SERD and potential new medicine camizestrant. 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. AstraZeneca is also exploring the potential 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 datopotamab deruxtecan-dlnk alone and in combination with immunotherapy 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 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's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit and follow the Company on social media @ AstraZeneca. References Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. doi: 10.3322/caac.21834. National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: Accessed June 2025. Scabia V, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun. 2022; 10.1038/s41467-022-30898-0. Cerner CancerMPact database. Accessed June 2025. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944. Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5):821-30. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available at: Accessed June 2025. Brett O, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor‑positive breast cancer. Breast Cancer Res. 2021; 23:85. Zundelevich, A, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020; 22:16. US-101612 Last updated 06/25
Yahoo
2 days ago
- Business
- Yahoo
Camizestrant reduced the risk of disease progression or death by 56% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 Phase III trial
First pivotal trial to demonstrate clinical value of monitoring circulating tumor DNA to detect and treat emerging resistance in 1st-line therapy ahead of disease progression in breast cancer First and only next-generation oral SERD and complete ER antagonist to demonstrate consistent progression-free survival benefit in combination with widely approved CDK4/6 inhibitors in 1st-line advanced breast cancer WILMINGTON, Del., June 01, 2025--(BUSINESS WIRE)--Positive results from 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 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 tumors have an emergent ESR1 mutation. These results will be presented today during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL (abstract #LBA4) and simultaneously published in The New England Journal of Medicine. Results showed the camizestrant combination reduced the risk of disease progression or death by 56% compared to standard-of-care treatment (based on a hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.31–0.60; p<0.00001) as assessed by investigator. Median PFS was 16.0 months for patients who switched to the camizestrant combination versus 9.2 months for the comparator arm. Importantly, a consistent PFS benefit was observed across all CDK4/6 inhibitors and clinically relevant subgroups in the trial, including analysis by age, race, region, time of ESR1 mutation detection and type of ESR1 mutation. The camizestrant combination was also associated with a meaningful delay in time to deterioration in quality of life, where in an exploratory endpoint, the camizestrant combination reduced the risk of deterioration in global health status and quality of life by 47% compared with the AI combination (HR 0.53; 95% CI, 0.33-0.82; nominal p<0.001). The median time to deterioration of global health status was 23.0 months in patients treated with the camizestrant combination, versus 6.4 months in patients that continued treatment with the AI combination (EORTC QLQ-C30). The camizestrant combination also delayed the time to deterioration of pain compared with the AI combination. Data for 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, a trend toward extended treatment benefit was observed with the camizestrant combination based on PFS2 (HR 0.52; 95% CI 0.33-0.81; p=0.0038 [interim analysis threshold p=0.0001]). The trial will continue to assess OS, PFS2 and other key secondary endpoints. Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, London, UK, and co-principal investigator for the trial, said: "Today's news marks a pivotal moment in breast cancer care and redefines how we think about drug resistance in this type of breast cancer. The results of the innovative SERENA-6 trial 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 more than halved the risk of disease progression or death and delayed deterioration in quality of life by nearly 18 months. This proactive approach exemplifies a new treatment strategy in oncology; by treating developing resistance before it causes disease progression and deterioration in quality of life, we can extend the benefit of 1st-line treatment to optimize patient outcomes." Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumor DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer. Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this 1st-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of HR-positive breast cancer." Summary of results: SERENA-6 Camizestrant + CDK4/6 inhibitor (n=155) AI + CDK4/6 inhibitor (n=155) PFSi Median PFS (months) 16.0 (12.7-18.2) 9.2 (7.2-9.5) Hazard ratio (95% CI) 0.44 (0.31-0.60) p-value p<0.00001 Time to deterioration in global health status/quality of lifeii Mean TTD (months) 23.0 (13.8-NC) 6.4 (2.8, 14.0) Hazard ratio (95% CI) 0.53 (0.33-0.82) p-value (nominal) p<0.001 PFS2iii Events 38 47 Hazard ratio (95% CI) 0.52 (0.33-0.81) p-value P=0.0038 [interim analysis threshold P=0.0001] CI, confidence interval; HR, hazard ratio; NC, not calculable; TTD, time-to-deterioration.i PFS was defined per RECIST v1.1. HR was estimated using the Cox proportional hazard model adjusted for stratification Assessments were conducted at baseline, weeks 4, 8 and 12 and then every 8 weeks until PFS2. Analysis conducted in patients with a baseline score and at least one post-baseline assessment. TTD in global health status/quality of life, an exploratory endpoint, was defined as the time from randomization to first deterioration that was confirmed at a subsequent timepoint measured using the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire (EORTC QLQ-30). Deterioration was defined as a decrease from baseline ≥16.6. HR was estimated using the Cox proportional hazard model stratified by time of ESR1 mutation detection (one test vs more than one test), and time from initiation of AI + CDK4/6i to randomization (<18 months vs. ≥18 months).iii HR was estimated using the Cox proportional hazard model adjusted for stratification factors. Final PFS2 analysis will occur at 158 PFS2 events. 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. Consistent with the longer duration of exposure to the combination of camizestrant and CDK4/6 inhibitors in the trial, Grade 3 or higher adverse events from all causes occurred in 60% of patients in the camizestrant arm versus 46% in the AI arm; the majority of which were hematological events typically associated with CDK4/6 inhibitor treatment and included neutropenia (45% vs. 34%), anemia (5% vs. 5%) and leukopenia (10% vs. 3%). If experienced, photopsia - reported as brief flashes of light in the peripheral vision - did not impact daily activities of patients in the trial and was reversible. There were no structural changes in the eye or changes in visual acuity. No new safety signals were identified and discontinuation rates were very low and similar in both arms, with 1% patients discontinuing camizestrant and 2% patients discontinuing an AI. Discontinuation of the CDK4/6 inhibitor occurred in 1% of patients in both arms of the trial. SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumor 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 tumor scans 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. Based on the results of the SERENA-6 Phase III trial, camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) has been granted Breakthrough Therapy Designation (BTD) in the US by the Food and Drug Administration for the treatment of adult patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer upon emergence of ESR1 mutation during first-line endocrine-based therapy. Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.1 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.2 HR-positive breast cancer, characterized by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumors considered HR-positive and HER2-negative.2 ERs often drive the growth of HR-positive breast cancer cells.3 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.4-6 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.6 Once this occurs, treatment options are limited and survival rates are low with 35% of patients anticipated to live beyond five years after diagnosis.2,6,7 Mutations in the ESR1 gene are a key driver of endocrine resistance and are widely tested for in clinical practice at time of disease progression on 1st-line therapies.8,9 These mutations emerge during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes.8,9 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment without disease progression.4 The optimization 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, randomized 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 tumors 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 program, 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 CDK4/6 inhibitors to address a number of areas of unmet need in HR-positive, HER2-negative 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 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-tumor profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors. 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 tumor environment. With fam-trastuzumab deruxtecan-nxki, 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 fulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, the TROP-2-directed ADC, datopotamab deruxtecan-dlnk and next-generation oral SERD and potential new medicine camizestrant. 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. AstraZeneca is also exploring the potential 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 datopotamab deruxtecan-dlnk alone and in combination with immunotherapy 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 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's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit and follow the Company on social media @AstraZeneca. References Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. doi: 10.3322/caac.21834. National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: Accessed June 2025. Scabia V, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun. 2022; 10.1038/s41467-022-30898-0. Cerner CancerMPact database. Accessed June 2025. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944. Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5):821-30. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available at: Accessed June 2025. Brett O, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor‑positive breast cancer. Breast Cancer Res. 2021; 23:85. Zundelevich, A, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020; 22:16. US-101612Last updated 06/25 View source version on Contacts Media Inquiries Fiona Cookson +1 212 814 3923Jillian Gonzales +1 302 885 2677 US Media Mailbox: usmediateam@ Sign in to access your portfolio
Yahoo
5 days ago
- Business
- Yahoo
Pfizer and Arvinas gamble to shift breast cancer treatment paradigm
Breast cancer (BC) is the most prevalent cancer among women globally with two million diagnosed cases each year. Oestrogen receptor (ER) is expressed in most invasive BC cases (70 to 80%). Many therapies have therefore been developed to target this receptor, including fulvestrant, and more recently the CDK4/6 inhibitors, which act synergistically with endocrine therapies. But following exposure to endocrine and CDK4/6 inhibitor therapy, many patients quickly acquire ER mutations (ESR1m), leading to treatment resistance and leaving a significant unmet need. Pfizer's and Arvinas' vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) ER degrader. The drug exploits the ubiquitin-proteasome system, degrading the mutant ER complex and greatly slowing growth and increasing tumour survivability. As the drug drives degradation and more specific targeting than small-molecule ER inhibitor receptors in preclinical studies, this class could leave a more profound effect with a tolerable safety profile. In the Phase II VERITAC trial, the drug was well-tolerated in a heavily CDK4/6 inhibitor pre-treated BC patient setting. Of 35 patients receiving 200mg of vepdegestrant, there was only one discontinuation and no dose reductions. A press release by Arvinas announced the results from the Phase III trial, VERITAC-2. Significant improvements to progression-free survival were seen with a hazard ratio of 0.60 in the ESR1m patient subpopulation for patients receiving vepdegestrant monotherapy compared to fulvestrant. This improvement was not seen in the overall population, including non-ESR1m patients. These patients had previously experienced progression following CDK4/6 inhibitor treatment. The full trial results are to be announced on 31 May at the 2025 American Society of Clinical Oncology conference. While initial safety and efficacy results are positive, the recent controversy surrounding the efficacy of CDK4/6 inhibitors in improving overall survival for breast cancer patients will hurt sales and the growth of the market share accessible to vepdegestrant. Regardless, the projected impact of vepdegestrant is suspected to be strong for the ESR1m population, which currently affects up to 39% of endocrine-resistant metastatic BC cases. GlobalData's analyst consensus forecasts estimate the drug to reach $1.64 billion in sales for metastatic breast cancer by 2031. "Pfizer and Arvinas gamble to shift breast cancer treatment paradigm" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site.
