Truqap plus Faslodex approved in Japan for patients with advanced HR-positive breast cancer

First and only AKT inhibitor approved in Japan for breast cancer patients with specific biomarker alterations (PIK3CA, AKT1 or PTEN)

Approval based on CAPItello-291 results which showed Truqap plus Faslodex reduced the risk of disease progression or death by 50% vs. 在生物标志物改变的人群中单独使用Faslodex
 

AstraZeneca’s Truqap 结合;结合 Faslodex (fulvestrant) has been approved in Japan for the treatment of adult patients with unresectable or recurrent PIK3CA, AKT1, 或pten改变的激素受体(HR)阳性, HER2-negative breast cancer following progression after treatment with endocrine therapy.

经日本厚生劳动省批准, Labour, 和福利(MHLW)的结果是基于 CAPItello-291 III期试验发表于 新英格兰医学杂志.¹ In the trial, Truqap in combination with Faslodex 疾病进展或死亡的风险降低了50% Faslodex alone in patients with tumours harbouring PI3K/AKT pathway biomarker alterations (based on hazard ratio of 0.50, 95%置信区间0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).¹

In Japan, more than 90,2022年，有1000名女性被诊断出患有乳腺癌, and more than 17,同年有000名病人死于这种疾病.² Globally, hr阳性乳腺癌(表达雌激素或孕激素受体), or both), 最常见的乳腺癌亚型是什么, with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.³ 总的来说，PIK3CA、AKT1的突变和PTEN的改变 occur frequently, affecting approximately 50% of patients with advanced HR-positive breast cancer.^4-6 在这种情况下，内分泌疗法被广泛使用, 通常与周期蛋白依赖性激酶(CDK) 4/6抑制剂联合使用, 但是一些肿瘤对这些疗法产生了耐药性, underscoring the need for additional combination approaches with endocrine therapy to extend time before the initiation of chemotherapy.⁷

Masakazu Toi, MD, PHD, 东京都癌症和传染病中心主任, Komagome Hospital, Japan said: “The approval of capivasertib and fulvestrant signifies a new era of care in advanced hormone receptor-positive breast cancer in Japan, providing a much-needed new treatment option for approximately half of patients in this setting who have tumours harbouring mutations in PIK3CA, AKT1 or alterations in PTEN. It is important for us to detect these specific tumour biomarker alterations in each patient we see, so that they are potentially able to benefit from this important combination to extend the effectiveness of endocrine-based treatment and delay disease progression.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said:
“乳腺癌是日本女性中最常见的癌症, and innovative, 迫切需要新的治疗方案. Today’s approval of Truqap, 一种一流的akt抑制剂, represents a significant step forward for HR-positive breast cancer treatment and an important new option for approximately fifty per cent of patients who have tumours with these specific mutations or alterations.”

在CAPItello-291试验中 Truqap plus Faslodex 是否与之前评估联合用药的试验中观察到的结果相似.¹

The MHLW have also approved a companion diagnostic test to detect the relevant alterations (PIK3CA, AKT1 and PTEN).

中国的监管申请目前正在审查中, the European Union, 还有其他几个国家, and this indication for Truqap in combination with Faslodex is already approved in the US 还有其他几个国家 based on results from the CAPItello-291 trial.

Financial considerations
在日本获得批准后, Astex Therapeutics is eligible to receive a milestone payment from AstraZeneca on first commercial sale of the drug in Japan as well as royalties on future sales in line with the agreement between the two companies.

Notes

HR-positive breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related death worldwide.⁸ 2022年，超过200万名患者被诊断出患有乳腺癌, with more than 665,000 deaths globally.⁸

hr阳性乳腺癌(表达雌激素或孕激素受体), or both), is the most common subtype of breast cancer with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.³

The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER), and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, 并且经常与CDK4/6抑制剂配对.^7,9,10 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.⁹ 一旦出现这种情况，治疗选择就有限了 – with chemotherapy being the current standard of care – and survival rates are low with approximately 30% of patients anticipated to live beyond five years after diagnosis.^3,9,11

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, 乳腺癌研究的活跃领域是什么.

CAPItello-291
CAPItello-291 is a Phase III, double-blind, randomised trial evaluating the efficacy of Truqap in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive, her2低或阴性(免疫组化)0或1+, 或IHC 2+/原位杂交(ISH)阴性)乳腺癌.

The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, 有或没有CDK4/6抑制剂, 对于晚期疾病，最多可以进行一次化疗. The trial has dual primary endpoints of PFS in the overall patient population and in a population of patients whose tumours have qualifying alterations in the PI3K/AKT pathway (PIK3CA, AKT1 or PTEN genes). In the trial, approximately 40% of tumours had these alterations and approximately 70% of patients received a prior CDK4/6 inhibitor.

Truqap
Truqap is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). Truqap 400mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition.

Truqap in combination with Faslodex is approved in the US, Japan 还有其他几个国家 for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1或PTEN)基于CAPItello-291试验的结果. Eligible patients will have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy.

Truqap is currently being evaluated in Phase III trials for the treatment of multiple subtypes of breast cancer and in other tumour types in combination with established treatments. The ongoing clinical research programme is focused on tumours reliant on signalling via the PI3K/AKT pathway, 在肿瘤中，这一途径的生物标志物发生了改变.

Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

Faslodex
Faslodex is an endocrine therapy indicated for the treatment of estrogen receptor-positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, 或在辅助抗雌激素治疗期间或之后疾病复发, 或者抗雌激素治疗的疾病进展.

In the US, EU and Japan, Faslodex is also approved in combination with CDK4/6 inhibitors for the treatment of women with HR-positive, her2阴性的晚期或转移性乳腺癌, 谁的癌症在接受内分泌治疗后进展了. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the estrogen receptor – a key driver of disease progression.

Faslodex is approved as monotherapy or in combination with medicines from various drug classes including CDK4/6, PI3K and AKT inhibitors for the treatment of patients with HR-positive advanced breast cancer and is being evaluated in combination with medicines from other drug classes.

澳门葡京网赌游戏治疗乳腺癌
由于对乳腺癌生物学的了解越来越深入, 澳门葡京网赌游戏开始挑战, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

With Enhertu (trastuzumab deruxtecan), her2导向抗体药物偶联物(ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap，以及下一代SERD和潜在新药卡米司腾. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. 澳门葡京网赌游戏与默沙东 & Co., Inc. 在美国和加拿大)继续研究 Lynparza 并探索其在早期疾病中的潜力.

To bring much-needed treatment options to patients with triple-negative breast cancer, 一种侵袭性乳腺癌, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap 结合化疗，和 Imfinzi 与其他肿瘤药物联合使用，包括 Lynparza and Enhertu.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, 开发并向患者提供改变生活的药物.

该公司专注于一些最具挑战性的癌症. 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.

澳门葡京网赌游戏的愿景是重新定义癌症治疗和, one day, 消除癌症作为死亡原因.

AstraZeneca
澳门葡京网赌游戏(LSE/STO/Nasdaq: AZN)是一家全球性制药公司, 以科学为主导的澳门葡京赌博游戏公司，专注于发现, development, 以及肿瘤学处方药的商业化, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit fitgreenlife.com 并在社交媒体上关注公司 @AstraZeneca.

Contacts
有关联络投资者关系组的详情，请按 here. For Media contacts, click here.

References