TOKYO, July 31, 2024 -- Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced today that it has concluded a license agreement with F. Hoffmann-La Roche Ltd (hereafter “Roche”) [Head Office: Basel, Switzerland. Thomas Schinecker] for inavolisib, a PI3K alpha inhibitor, currently in development for advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation in combination with palbociclib and fulvestrant.

东京，2024年7月31日——Chugai Pharmaceutical Co.，Ltd.（东京：4519）今天宣布，它已经与F.Hoffmann La Roche Ltd（以下简称“Roche”）[总部：瑞士巴塞尔，Thomas Schinecker]就PI3Kα抑制剂inavolisib达成了许可协议，目前正在开发中，用于晚期激素受体阳性，HER2阴性的乳腺癌，其PIK3CA突变与palbociclib和氟维司群联合使用。

Under the license agreement between Roche and Chugai, Chugai obtained exclusive rights for the development and marketing of inavolisib in Japan. Roche will receive an upfront fee and milestone payments..

根据罗氏和Chugai之间的许可协议，Chugai获得了在日本开发和销售inavolisib的专有权。罗氏将收到预付费和里程碑付款。。

“PIK3CA mutations are detected in approximately 40%1 of patients with hormone receptor (HR)-positive breast cancer. Patients with PIK3CA mutated HR-positive, HER2 negative advanced BC have a poorer prognosis and thus there remains a significant unmet need for this patient group. Inavolisib, which has shown positive data in global clinical trials, is expected to be a new treatment option for patients with breast cancer.

“大约40%的激素受体（HR）阳性乳腺癌患者检测到PIK3CA突变。PIK3CA突变HR阳性，HER2阴性的晚期BC患者预后较差，因此该患者组的需求仍显着未得到满足。Inavolisib在全球临床试验中显示出阳性数据，有望成为乳腺癌患者的新治疗选择。

Chugai will work closely with Roche to conduct domestic development in order to bring inavolisib to patients with breast cancer as soon as possible,” said Chugai’s President and CEO, Dr. Osamu Okuda..

Chugai将与罗氏公司密切合作，进行国内开发，以便尽快将inavolisib带给乳腺癌患者，”Chugai总裁兼首席执行官OsamuOkuda博士说。。

Inavolisib was discovered by Genentech, a member of the Roche Group, and is currently under development for two global Phase III clinical studies in patients with locally advanced or metastatic HR-positive/HER2-negative breast cancer with PIK3CA mutations (INAVO120 and INAVO121) and one global Phase III clinical study in patients with PIK3CA mutated HER2-positive breast cancer (INAVO122).

Inavolisib是由罗氏集团（Roche Group）成员基因泰克（Genentech）发现的，目前正在开发两项针对局部晚期或转移性HR阳性/HER2阴性乳腺癌伴PIK3CA突变（INAVO120和INAVO121）患者的全球III期临床研究，以及一项针对PIK3CA突变HER2阳性乳腺癌（INAVO122）患者的全球III期临床研究。

The INAVO120 study demonstrated that the inavolisib-based regimen (in combination with palbociclib and fulvestrant) more than doubled progression-free survival, reducing the risk of disease worsening or death by 57% compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.0001) in the first-line setting.

INAVO120研究表明，与单独使用palbociclib和氟维司群相比，基于inavolisib的方案（联合使用palbociclib和氟维司群）的无进展生存期增加了一倍以上，疾病恶化或死亡风险降低了57%（15.0个月比7.3个月；风险比[HR]=0.43，95%CI:0.32-0.59，p＜0.0001）。

The inavolisib-based regimen has also been shown to be well tolerated with a manageable safety profile.Based on the positive results of the INAVO120 study, inavolisib has been granted Breakthrough Therapy Designation for the treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer with PIK3CA mutations in the first-line setting as well as Priority Review by the U.S.

基于inavolisib的方案也被证明具有良好的耐受性和可控的安全性。根据INAVO120研究的阳性结果，inavolisib已被授予突破性治疗指定，用于治疗HR阳性，HER2阴性的局部晚期或转移性乳腺癌，并在一线治疗中具有PIK3CA突变，以及美国的优先审查。

Food and Drug Administration (FDA) for the new drug application with a PDUFA date of November 27, 2024.

食品和药物管理局（FDA）的新药申请，PDUFA日期为2024年11月27日。

Chugai will continue to effectively utilize the research and development resources of the Roche Group to find innovative new drugs so as to satisfy unmet medical needs.

楚盖将继续有效利用罗氏集团的研发资源，寻找创新新药，以满足未满足的医疗需求。

About inavolisib Inavolisib is an investigational, oral targeted treatment that could provide well-tolerated, durable disease control and potentially improved outcomes for people with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer.

关于inavolisib inavolisib是一种研究性口服靶向治疗，可为PIK3CA突变，激素受体阳性，人表皮生长因子受体2阴性，局部晚期或转移性乳腺癌患者提供耐受性良好，持久的疾病控制和潜在改善的结果。

Inavolisib has been designed to help minimize the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha..

Inavolisib旨在帮助最大程度地减少治疗的总体负担和毒性，并且由于其对PI3Kα亚型与其他亚型的高效力和特异性，以及促进突变PI3Kα降解的独特作用机制，与其他PI3K抑制剂有所不同。。

About the INAVO120 study The INAVO120 study is a global Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of inavolisib in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease..

关于INAVO120研究INAVO120研究是一项全球III期，随机，双盲，安慰剂对照研究，评估inavolisib联合palbociclib和氟维司群与安慰剂联合palbociclib和氟维司群对PIK3CA突变，激素受体（HR）阳性，人表皮生长因子受体2（HER2）阴性，局部晚期或转移性乳腺癌患者的疗效和安全性，这些患者的疾病在治疗期间或完成辅助内分泌治疗后12个月内进展，并且之前没有接受过转移性疾病的全身治疗。。

The study included 325 patients. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.

该研究包括325名患者。主要终点是无进展生存期（PFS）。次要终点包括总生存率，客观缓解率和临床获益率。

The INAVO120 study met its primary endpoint, extending PFS by 7.7 months compared to the control group, demonstrating the superiority of the combination of inavolisib, palbociclib and fulvestrant (hazard ratio, 0.43 [95% CI = 0.32, 0.59]; p<0.0001)2. Regarding safety, the incidence of hyperglycemia, diarrhea, stomatitis, nausea, and skin rash was higher in the inavolisib group compared to the control group, but most of these events were Grade 1-2 (incidence of Grade 3-4 events was hyperglycemia: 5.6%, stomatitis: 5.6%, diarrhea: 3.7%, nausea: 0.6%, and skin rash: 0%), confirming that the inavolisib was well tolerated and the safety profile was manageable..

INAVO120研究达到了其主要终点，与对照组相比，PFS延长了7.7个月，证明了inavolisib，palbociclib和氟维司群联合治疗的优越性（风险比为0.43[95%CI=0.32,0.59]；p<0.0001）2。关于安全性，与对照组相比，inavolisib组的高血糖，腹泻，口腔炎，恶心和皮疹的发生率更高，但大多数事件为1-2级（3-4级事件的发生率为高血糖：5.6%，口腔炎：5.6%，腹泻：3.7%，恶心：0.6%，皮疹：0%），证实inavolisib耐受性良好，安全性可控。。

About Hormone Receptor-Positive Breast Cancer HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70%3 of cases. A defining feature of HR-positive breast cancer is that its tumor cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumor growth.

关于激素受体阳性乳腺癌HR阳性乳腺癌是所有乳腺癌中最普遍的类型，约占病例的70%。HR阳性乳腺癌的一个决定性特征是其肿瘤细胞具有与一种或两种激素（雌激素或孕激素）结合的受体，这可能有助于肿瘤的生长。

People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. The PI3K signaling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.

被诊断患有HR阳性转移性乳腺癌的人通常面临疾病进展和治疗副作用的风险，因此需要额外的治疗选择。PI3K信号通路通常在HR阳性乳腺癌中失调，通常是由于激活PIK3CA突变，这已被确定为与细胞周期蛋白依赖性激酶4/6抑制剂联合使用对标准内分泌治疗产生内在抗性的潜在机制。