A Randomized, Double-Blind, Placebo-Controlled, 2-Cohort, Phase III Study of Saruparib Combined With Physician's Choice of Androgen Receptor Pathway Inhibitor in Patients With Metastatic Hormone-Sensitive Prostate Cancer, Previously Treated With Docetaxel or PSMA-directed 177Lutetium-Containing Therapy Without Disease Progression, and With Prostate-Specific Antigen ≥ 0.2 ng/mL: EvoPAR-Prostate05

The primary objective of this study is to measure efficacy of saruparib + physician's choice of ARPI compared with placebo + ARPI in men with metastatic hormone-sensitive prostate cancer (mHSPC) who have previously received docetaxel chemotherapy or a prostate-specific membrane antigen (PSMA)-directed lutetium-177 radioligand therapy with no evidence of disease progression and PSA ≥ 0.2 ng/mL.

Start Date01 Oct 2026

Sponsor / Collaborator

AstraZeneca PLC

NCT07446855

/ RecruitingPhase 1/2

A Modular Open-label, Phase I/IIa Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Ascending Doses of AZD4956 as Monotherapy, and in Combination With Anti-Cancer Agents in Participants With Advanced/Metastatic Homologous Recombination Repair Defective Solid Tumours

The purpose of this modular, first trial in human study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of ascending dose levels (DLs) of AZD4956 monotherapy and in combination with other anti-cancer agents in participants with advanced/metastatic solid tumours with homologous recombination repair (HRR) deficiencies.

Start Date17 Mar 2026

Sponsor / Collaborator

AstraZeneca PLC

NCT07336446

/ RecruitingPhase 1/2

A Phase I/II, Modular, Open-Label, Multi-Centre Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD9750 as Monotherapy and in Combination With Other Anticancer Agents in Participants With Metastatic Prostate Cancer (ANDROMEDA)

ANDROMEDA is a first-in-human, Phase I/II, open-label, multicenter study of AZD9750 in participants with metastatic prostate cancer. The trial evaluates safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of AZD9750 as monotherapy and in combination with saruparib.

Start Date27 Jan 2026

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with Saruparib

100 Translational Medicine associated with Saruparib

100 Patents (Medical) associated with Saruparib

Literatures (Medical) associated with Saruparib

01 Aug 2026·BIOMEDICINE & PHARMACOTHERAPY

Resistance-centered pharmacology of DNA damage response-targeted therapy: Mechanisms, predictive biomarkers, and biomarker-guided adaptive treatment strategies in solid tumors

Review

Author: An, Jeongmin ; Zhao, Fei ; Qin, Sisi ; Kim, Wootae ; Qiao, Wang ; Zhichao, Xu ; Seo, Gayoung ; Siyao, Tang

DNA damage response (DDR)-targeted agents, particularly poly(ADP-ribose) polymerase inhibitors (PARPi), have transformed treatment of homologous recombination (HR)-deficient solid tumors. Yet inevitable therapeutic resistance limits durability of clinical benefit and now defines the central pharmacological challenge of the field, driving development of next-generation DDR inhibitors including saruparib, ART6043, RP-3467, ART0380/alnodesertib, ceralasertib, and peposertib. Existing reviews predominantly catalog DDR around isolated pathways or individual drug classes, failing to capture resistance as a cross-pathway, network-level pharmacological phenomenon. Here, we provide a resistance-mechanism-centered pharmacological framework that systematically connects DDR protein alterations, predictive biomarkers, and matched therapeutic strategies into a unified, clinically actionable roadmap. Pan-cancer analysis of TCGA Pan-Cancer Atlas data (10,348 tumors across 31 cancer types) reveals statistically significant pathway co-alteration patterns (Spearman ρ = 0.76-0.89; FDR < 0.05) that reframe DDR dysfunction as coordinated network-level disruption rather than isolated single-pathway loss. We classify clinical resistance into six mechanistically distinct categories - BRCA1/2 reversion mutations, 53BP1/Shieldin-mediated HR restoration, replication fork stabilization, Polθ-mediated theta-mediated end joining, ABCB1-driven drug efflux, and cGAS-STING-mediated immune evasion - and pharmacologically map each to detectable biomarkers and matched therapeutic strategies, supported by 2024-2026 clinical trial data including PETRA, EvoPAR-Prostate01/02, STELLA, MEDIOLA, TOPACIO, ATHENA-COMBO, CAPRI, and the practice-changing DUO-O trial. We propose a biomarker-guided adaptive treatment algorithm integrating longitudinal circulating tumor DNA monitoring, functional RAD51 foci assays, and AI-driven multi-omics integration to enable real-time resistance detection and mechanism-guided therapy switching. This framework advances DDR-targeted oncology from static biomarker selection toward a dynamic, resistance-aware, mechanism-matched therapeutic strategy for patients with metastatic solid tumors.

01 Jun 2026·BIOORGANIC CHEMISTRY

Discovery of selective PARP1/CDK6 dual target inhibitors modulating Wnt signaling pathway for the treatment of TNBC

Article

Author: Zheng, Keying ; Wang, Cheng ; Li, Na ; Lai, Yiling ; Fan, Heqing ; Liu, Fanglan ; Zeng, Jingting ; Fan, Yongwei ; Xia, Chunhua

The combination of PARP1 and CDK6 inhibitors shows synergistic anticancer effects in TNBC. However, first-generation PARP inhibitors lack optimal PARP trapping efficiency and enzyme family selectivity, often leading to hematotoxicity. Herein, we report the rational design and synthesis of a series of second-generation selective PARP1/CDK6 dual inhibitors, based on the structural features of the latest selective PARP1 inhibitor AZD5305. Among these, PC8 exhibits potent dual inhibition of PARP1 (IC₅₀ = 0.126 μM) and CDK6 (IC₅₀ = 0.197 μM), showing selectivity over PARP2 (IC₅₀ = 0.824 μM). PC8 effectively inhibits the proliferation and migration of TNBC cells, and induces intracellular ROS accumulation, thereby exacerbating mitochondrial dysfunction and DNA damage. Additionally, it modulates the classical Wnt signaling pathway. Furthermore, compared with first-generation inhibitors, PC8 displays improved metabolic stability in liver microsomes. As a novel selective PARP1/CDK6 dual inhibitor with improved pharmacological properties, PC8 represents a promising lead structure for further optimization of second-generation PARP1/CDK6 dual inhibitors for the treatment of TNBC.

01 May 2026·Cell Reports

PARP1-specific inhibitor displays PARP1-detrapping activity

Article

Author: Laker, Ellen ; Smith, Rebecca ; Suskiewicz, Marcin J ; Simmons, Michael D R ; Zobel, Florian F H ; Chatrin, Chatrin ; Baretić, Domagoj ; Tsang, Kyle ; Schützenhofer, Kira ; Ahel, Ivan

The successful use of PARP inhibitors against primarily homologous recombination-deficient tumors relies on their ability to inhibit the catalytic activity of PARP1 and PARP2, leading to their retention at sites of DNA damage, known as PARP "trapping." Different PARP inhibitors vary in their trapping ability and thus in their resulting toxicity. Here, we develop an inducible complementation system for the expression of tagged PARP1 variants to assess the impact of different mutations in the PARP1 catalytic site on ADP-ribosylation (ADPr) activity, trapping, and cell survival. Testing these cell lines for their behavior and sensitivity to different PARP inhibitors, we find that saruparib, a first-in-class PARP1-specific inhibitor, promotes the release of certain PARP1 catalytic mutants and resistance to this inhibitor. We also characterize a PARP1 catalytic mutant with intact mono(ADP-ribosyl)ation activity but devoid of poly(ADP-ribosyl)ation, enabling us to demonstrate a significant contribution of mono(ADP-ribosyl)ation toward PARP1 release from sites of DNA damage.

News (Medical) associated with Saruparib

24 Jul 2026

·www.astrazeneca.com

Enhertu plus pertuzumab recommended for approval in the EU by CHMP as 1st-line treatment for patients with HER2-positive metastatic breast cancer

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) in combination with pertuzumab has been recommended for approval in the European Union (EU) for the 1st-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the DESTINY-Breast09 Phase III trial presented at the 2025 American Society of Clinical Oncology Annual Meeting and subsequently published in The New England Journal of Medicine.1 Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “HER2-positive metastatic breast cancer is an aggressive subtype, so starting patients on an effective HER2-targeted treatment early and continuing it for as long as they benefit can have a meaningful impact on long-term outcomes. DESTINY-Breast09 sets a new benchmark with a median progression-free survival of more than three years, underscoring the potential of Enhertu plus pertuzumab to redefine first-line treatment for patients with HER2-positive metastatic breast cancer.” John Tsai, Global Head, R&D, Daiichi Sankyo, said: “Enhertu in combination with pertuzumab improved progression-free survival by more than one year compared with the current first-line standard of care, representing a meaningful advantage early in the treatment of patients with metastatic HER2-positive disease. Today’s positive CHMP opinion brings us closer to making Enhertu available in the EU as a first-line treatment option for eligible patients with HER2-positive metastatic breast cancer, marking an important milestone in moving this medicine earlier in the treatment pathway.” In DESTINY-Breast09, Enhertu in combination with pertuzumab reduced the risk of disease progression or death by 44% versus a taxane, trastuzumab and pertuzumab (THP) (based on a hazard ratio of 0.56; 95% confidence interval [CI]: 0.44-0.71; p<0.00001) in patients with HER2-positive metastatic breast cancer who had not received prior chemotherapy or HER2-targeted therapy or had received neoadjuvant or adjuvant HER2-targeted therapy more than six months before the diagnosis of advanced or metastatic disease. Median progression-free survival (PFS) was 40.7 months with Enhertu in combination with pertuzumab compared to 26.9 months with THP. The PFS benefit was consistent across subgroups, including for the prespecified stratification factorsof hormone receptor status, de novo or recurrent disease and PIK3CA mutation status. The safety profile of Enhertu plus pertuzumab was consistent with the known profiles of each individual therapy with no new safety concerns identified. Enhertu in combination with pertuzumab is approved in the US, Switzerland and other countries as a 1st-line treatment for patients with metastatic HER2-positive breast cancer based on the results from the DESTINY-Breast09 trial. Enhertu is also under review in the EU for patients with HER2-positive breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment based on data from the DESTINY-Breast05 trial. Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. Notes HER2-positive metastatic breast cancer Breast cancer is the most common cancer in women worldwide and the leading cause of cancer-related death among women.2 Approximately, 2.4 million breast cancer cases were diagnosed in 2024, with more than 690,000 deaths globally.2 In Europe, approximately 540,000 cases of breast cancer are diagnosed annually, with more than 140,000 deaths.3 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or whose disease has progressed 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 tumours including breast cancer.5 HER2 protein overexpression may occur as a result of HER2 gene amplification.4 Approximately one in five cases of breast cancer is considered HER2-positive.5 HER2-positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 that affects 15% to 20% of patients with metastatic breast cancer.6 While HER2-targeted therapies have improved outcomes, prognosis remains poor with most patients experiencing disease progression within two years of first-line treatment with THP, which has been the standard of care for more than a decade.6-8 Further, approximately one in three patients do not receive any treatment following first-line therapy due to disease progression or death.10,11 DESTINY-Breast09 DESTINY-Breast09 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP as first-line treatment in patients with HER2-positive metastatic breast cancer who had not received prior chemotherapy or HER2-targeted therapy or had received neoadjuvant or adjuvant HER2-targeted therapy more than six months before the diagnosis of advanced or metastatic disease. Patients were randomised 1:1:1 to receive either Enhertu monotherapy with a pertuzumab matching placebo; Enhertu in combination with pertuzumab; or THP. Randomisation was stratified by prior treatment (de novo metastatic disease versus progression from early-stage disease), hormone receptor (HR) status and PIK3CA mutation status. The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR in both the Enhertu monotherapy and Enhertu combination arms. Secondary endpoints include investigator-assessed PFS, overall survival, ORR, duration of response, pharmacokinetics and safety. The investigational arm assessing Enhertu monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis. DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, 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, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Enhertu (5.4mg/kg) followed by THP is approved in the US, China and Singapore as a neoadjuvant treatment for adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer based on the results from the DESTINY-Breast11 trial. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (5.4mg/kg) is approved in the US as an adjuvant treatment for adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following trastuzumab (with or without pertuzumab) and taxane-based treatment based on the DESTINY-Breast05 trial. Enhertu (5.4mg/kg) in combination with pertuzumab is approved in the US, Switzerland, India, Israel, United Arab Emirates, Saudi Arabia, Korea and Singapore as a 1st-line treatment for adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer based on the results from the DESTINY-Breast09 trial. Enhertu (5.4mg/kg) is approved in more than 100 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a 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/regions worldwide 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 locally or regionally authorised test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. Enhertu (5.4mg/kg) is approved in more than 100 countries/regions 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 (5.4mg/kg) is approved in more than 80 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours 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 90 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 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-Gastric04 trials. Enhertu (5.4mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and/or HERALD trials. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu clinical development programme A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as a monotherapy, in combination or sequentially with other cancer medicines across multiple HER2-targetable cancers. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) 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 Datroway. 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, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and expanding 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, Etcamah. 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. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with Etcamah 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/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, 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 Oncology Corporate and financial

Clinical ResultDrug ApprovalPhase 3License out/inASCO

23 Jul 2026

·www.astrazeneca.com

Etcamah (camizestrant) in combination with a CDK4/6 inhibitor approved in the EU for 1st-line advanced ER-positive breast cancer

AstraZeneca’s Etcamah (camizestrant) in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) has been approved in the European Union (EU) for the treatment of adult patients with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer upon detection of ESR1 mutation and without disease progression during 1st-line endocrine therapy in combination with a CDK4/6 inhibitor. The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and was based on the positive results from the pivotal SERENA-6 Phase III trial published in The New England Journal of Medicine.1 In a planned interim analysis, the Etcamah combination reduced the risk of disease progression or death by 56% versus standard-of-care treatment with an aromatase inhibitor (AI) (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (based on a hazard ratio [HR] of 0.44; 95% confidence interval [CI]:0.31-0.60; p<0.00001; median progression-free survival (PFS) 16.0 versus 9.2 months). In Europe, breast cancer remains the leading cause of cancer death among women, with more than 140,000 deaths in 2024 and more than 540,000 patients diagnosed in the same year.2 Hormone receptor (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.3 More than 97% of HR-positive breast cancer tumours are ER-positive.4,5 Across the UK, France, Germany, Spain and Italy, approximately 37,000 patients with HR-positive metastatic breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies paired with CDK4/6 inhibitors.6-8 However, many patients have tumours that develop resistance to these therapies, at which point treatment options are limited and survival rates are low, with only approximately 36% of patients anticipated to live beyond five years after diagnosis.3,8 Mutations in the ESR1 gene are a key driver of endocrine resistance and are associated with poor outcomes, emerging during treatment of the disease and becoming more prevalent as the disease progresses.9,10 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment before disease progression.6 François-Clément Bidard MD, PhD, Professor of Medical Oncology at Institut Curie & Versailles University (Paris/Saclay) France and co-principal investigator for the trial, said: “Today’s approval is welcome news for the one in three patients in Europe with this form of advanced breast cancer whose tumours develop ESR1 mutations before disease progression and are in urgent need of new options that both delay this progression and extend the benefit of 1st-line treatments. As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumour DNA in the 1st-line breast cancer setting, SERENA-6 represents a significant advance in clinical practice and it is now important to identify patients who may be able to benefit from this combination and intervene promptly before their disease progresses.” Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “The approval of the Etcamah combination marks an important shift in the 1st-line treatment paradigm for patients with ER-positive, HER2-negative advanced breast cancer in Europe, providing a new standard-of-care to address emerging resistance ahead of disease progression. It also reflects the strength of AstraZeneca’s oncology pipeline and our commitment to translate innovative science into practice-changing treatment options for patients.” Data for the key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of the interim analysis of the SERENA-6 trial, however, a subsequent pre-planned analysis demonstrated a statistically significant and clinically meaningful PFS2 benefit of 25.7 months versus 19.1 months in favour of the Etcamah combination (HR: 0.63; 95% CI: 0.46-0.86; p=0.00373) and OS continued to mature in favour of the Etcamah combination (HR: 0.87; 95% CI: 0.57-1.30). The trial will continue to assess OS as a key secondary endpoint. The safety profile of Etcamah in combination with palbociclib, ribociclib or abemaciclib in the SERENA-6 trial 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.1 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 innovative trial design used ctDNA monitoring via a blood test at the time of routine tumour scans every two to three months to identify patients for early signs of endocrine resistance via the emergence of ESR1 mutations. Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to Etcamah from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor. Etcamah is also approved in Japan, the United Arab Emirates and Saudi Arabia based on the SERENA-6 Phase III trial. Regulatory applications for Etcamah in this setting are currently under review in several other countries including the US where the US Food and Drug Administration recently extended the Prescription Drug User Fee Act date to review the updated results from the trial. Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.11 More than two million patients were diagnosed with breast cancer in 2024, with more than 690,000 deaths globally.11 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.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 ER-driven disease, which are often paired with CDK4/6 inhibitors.6-8 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 Etcamah 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. Etcamah Etcamah (camizestrant) is a potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist, administered orally, once daily. The recommended dose of Etcamah in combination with a CDK4/6 inhibitor is 75mg. Etcamah in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) is approved in the EU, Japan and several other countries for the treatment of adult patients with HR-positive (or ER-positive), HER2-negative locally advanced or metastatic breast cancer upon detection or emergence of ESR1 mutation and without disease progression during 1st-line endocrine therapy based on the results from the SERENA-6 trial. The broad, robust and innovative Etcamah clinical development programme, including the SERENA-4, CAMBRIA-1 and CAMBRIA-2 Phase III trials, is evaluating the safety and efficacy of Etcamah 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. Etcamah 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 a statistically significant and clinically meaningful improvement in PFS versus Faslodex (fulvestrant) in the overall trial population, including in patients with ESR1 tumour mutations irrespective of 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. 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 antibody drug conjugate (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, Etcamah. 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. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with Etcamah 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/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, 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 Matthew Bowden Company Secretary AstraZeneca PLC Oncology Corporate and financial

Clinical ResultPhase 3Phase 1Drug ApprovalImmunotherapy

26 Jun 2026

·www.astrazeneca.com

AstraZeneca and Daiichi Sankyo’sDatroway (datopotamab deruxtecan) has been recommended for approval in the European Union (EU) as monotherapy for the 1st-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the TROPION-Breast02 Phase III trial, which were presented at the 2025 European Society for Medical Oncology Congress and published in Annals of Oncology. Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “As one of the hardest cancers to treat, today only 15% of patients with metastatic triple-negative breast cancer survive beyond five years. This positive opinion from the CHMP marks an important step forward in bringing the potential of Datroway to transform outcomes for patients with this type of cancer in the EU.” John Tsai, MD, Global Head, R&D, Daiichi Sankyo, said: “Triple-negative breast cancer remains one of the most aggressive types of breast cancer, with limited treatment options for patients with metastatic disease who are not candidates for immunotherapy and are currently treated with traditional chemotherapy. This positive recommendation by the CHMP underscores the potential for Datroway to replace traditional chemotherapy in this setting and we look forward to working closely with the EMA to bring this new indication to patients in the EU.” In the trial, Datroway demonstrated a statistically significant and clinically meaningful 5.0-month improvement in median overall survival (OS) (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.64-0.98; p=0.0291) compared to chemotherapy as 1st-line treatment in this patient population. Median OS was 23.7 months for patients treated with Datroway versus 18.7 months for those treated with chemotherapy. Datroway reduced the risk of disease progression or death by 43% compared to chemotherapy (HR 0.57; 95% CI 0.47-0.69; p<0.0001) as assessed by blinded independent central review (BICR). Datroway was also associated with more robust treatment responses, including an objective response rate (ORR) of 62.5% compared to an ORR of 29.3% with chemotherapy.1 The safety profile of Datroway in TROPION-Breast02 was consistent with previous clinical trials of Datroway in breast cancer. Datroway was approved in the US in May 2026 for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy. Additional reviews are underway in China and Japan, as well as Australia, Canada, Singapore and Switzerland as part of Project Orbis. Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. Notes Triple-negative breast cancer TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.2,3 In Europe, there are an estimated 83,000 diagnoses of TNBC each year.2,4 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.5-7 Metastatic TNBC is the most aggressive type of breast cancer and has one of the worst prognoses, with median OS of just 12 to 18 months and only about 15% of patients living five years following diagnosis.5,8,9 While some breast cancers may test positive for oestrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.5 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.5 For patients with metastatic disease with PD-L1 expressing tumours, the addition of immunotherapy to chemotherapy has improved outcomes in the 1st-line setting.10,11However, for approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, prior to the approval of Datroway, chemotherapy was the standard 1st-line treatment.12 TROP2 is a protein broadly expressed in several solid tumours, including TNBC.13 TROP2 is associated with increased tumour progression and poor survival in patients with breast cancer.14,15 TROPION-Breast02 TROPION-Breast02 is a global, multicentre, randomised, open-label Phase III trial evaluating the efficacy and safety of Datroway versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumours did not express PD-L1 as well as patients with PD-L1 expressing tumours who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrolment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as stable brain metastases. The dual primary endpoints of TROPION-Breast02 are OS and progression-free survival (PFS) as assessed by blinded independent central review. Secondary endpoints include PFS as assessed by investigator, ORR, duration of response, disease control rate, pharmacokinetics and safety. TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For more information, visit ClinicalTrials.gov. Datroway Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the US only) is a TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Datroway is one of seven DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Datroway is also approved in more than 40 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on results from the TROPION-Breast01 trial. Datroway is approved in the US for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy based on the results from the TROPION-Breast02 trial. Datroway is available in the US under accelerated approval for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy based on results from the TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. Datroway clinical development programme A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including NSCLC, TNBC and urothelial cancer. The programme includes eight Phase III trials in lung cancer, five Phase III trials in breast cancer, and one Phase II/III trial in urothelial cancer evaluating Datroway as a monotherapy and in combination with other cancer treatments in various settings. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu (trastuzumab deruxtecan) in March 2019 and Datroway 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 Datroway. 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, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and expanding 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 first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway, and next-generation oral SERD, Etcamah. 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. 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 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/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, 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 Matthew Bowden Company Secretary AstraZeneca PLC Oncology Corporate and financial

Phase 3ImmunotherapyClinical ResultDrug Approval

100 Deals associated with Saruparib

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Hormone-dependent prostate cancer	Phase 3	Canada	AstraZeneca PLC	01 Oct 2026
Adenocarcinoma of prostate	Phase 3	United States	AstraZeneca PLC	06 Aug 2025
Adenocarcinoma of prostate	Phase 3	China	AstraZeneca PLC	06 Aug 2025
Adenocarcinoma of prostate	Phase 3	Japan	AstraZeneca PLC	06 Aug 2025
Adenocarcinoma of prostate	Phase 3	Argentina	AstraZeneca PLC	06 Aug 2025
Adenocarcinoma of prostate	Phase 3	Australia	AstraZeneca PLC	06 Aug 2025
Adenocarcinoma of prostate	Phase 3	Austria	AstraZeneca PLC	06 Aug 2025
Adenocarcinoma of prostate	Phase 3	Belgium	AstraZeneca PLC	06 Aug 2025
Adenocarcinoma of prostate	Phase 3	Brazil	AstraZeneca PLC	06 Aug 2025
Adenocarcinoma of prostate	Phase 3	Canada	AstraZeneca PLC	06 Aug 2025

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05367440 (PETRANHA, ASCO_GU2026)	Phase 1/2	Hormone-dependent prostate cancer homologous recombination repair mutation (HRRm)	93	Saruparib + ARPI + ADT	dgwnramgtm(styeippsdf) = xsqlegamwb gfegvvwsol (noleulnkfz ) View more	Positive	26 Feb 2026
NCT05367440 (PETRANHA, ASCO_GU2026)	Phase 1/2		93	Saruparib + ARPI + ADT (HRRm)	taztrljoqy(zkcoqwtsqw) = kbhjneoeve jemilziahm (bxbekfhwtq, 50.0 - 100.0) View more	Positive	26 Feb 2026
NCT04644068 (PETRA, SABCS2025)	Phase 1/2	Recurrent HER2-Negative Breast Carcinoma ER positive \| HER2 negative \| BRCA1/2 mutation ... View more	38	Saruparib + Camizestrant	ibmlkmqdni(dyrvopgmqo) = ildpbxccej kgjkqfsbsg (xwdszuepxt ) View more	Positive	10 Dec 2025
NCT04644068 (PETRA, SABCS2025)	Phase 1/2		38	Saruparib + Camizestrant (BRCA1/BRCA2 mutation or PALB2 mutation)	whdwwgfddu(gxgvcupvbw) = bwunztdfkz buoglyaasa (hmchjrhleb, 4.4 - 7.3)	Positive	10 Dec 2025
NCT04644068 (PETRA, AACR2024) Manual	Phase 1/2	Advanced Malignant Solid Neoplasm PALB2 Mutation \| RAD51C Mutation \| BRCA2 Mutation \| ... View more	141	Saruparib	uemnjrrpwg(nlxymvbajz) = xfpbvwussr zllzrmtyjv (ppfbuyhior, 35.7 - 61.3) View more	Positive	08 Apr 2024
NCT05367440 (PETRANHA, ASCO_GU2024) Manual	Phase 1/2	Metastatic Prostate Carcinoma	48	enzalutamide or abiraterone acetate or darolutamide+AZD5305	avkhghfpir(uzniytqrrs) = zpxhpbbdor mzaxhdgqhw (pzxfzocczj ) View more	Positive	25 Jan 2024
NCT05123482 (Pubmed \| Clin Cancer Res)	Phase 1	Ovarian Cancer \| Endometrial Carcinoma \| Advanced Malignant Solid Neoplasm ... homologous recombination repair deficiency \| elevated levels of B7-H4 View more	-	AZD8205	czjszogxtl(ifhiskvcvc) = jmrduhylpz qzhbiyjeqb (dckxjfqhlf )	-	14 Mar 2023
NCT04644068 (PETRA, AACR2022) Manual	Phase 1	Ovarian Cancer \| Breast Cancer \| Prostatic Cancer ... BRCA1 Mutation \| BRCA2 Mutation \| PALB2 Mutation ... View more	46	AZD5305	hggrejbwys(tabcdpppmq) = cgibqmjosj mradsmdvyc (irawannwuc ) View more	Positive	15 Jun 2022

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