TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Initial results from dose escalation in the first-in-human phase 1 trial of DS-9606 suggest early promising clinical activity in patients with advanced solid tumors known to express Claudin-6 (CLDN6). These data were presented today during a Proffered Paper session (610O) at the 2024 European Society for Medical Oncology (#ESMO24)..

东京和新泽西州巴斯金岭（BUSINESS WIRE）--DS-9606首次人体1期临床试验中剂量递增的初步结果表明，已知表达Claudin-6（CLDN6）的晚期实体瘤患者的早期有希望的临床活性。这些数据今天在2024年欧洲肿瘤内科学会（ESMO24）的一次论文会议（6100）上发表。。

DS-9606 is an investigational CLDN6 directed, modified pyrrolobenzodiazepine (PBD) antibody drug conjugate (ADC) from Daiichi Sankyo’s (TSE: 4568) second antibody drug conjugate (ADC) platform.

DS-9606是来自Daiichi Sankyo（TSE:4568）第二抗体-药物缀合物（ADC）平台的研究性CLDN6指导的修饰吡咯苯并二氮杂卓（PBD）抗体-药物缀合物（ADC）。

CLDN6 is expressed in several tumor types including endometrial, ovarian and gastric cancers, germ cell tumors (GCT) and non-small cell lung cancer (NSCLC), and can be associated with poor prognosis, making CLDN6 a promising therapeutic target.1-6

CLDN6在几种肿瘤类型中表达，包括子宫内膜癌，卵巢癌和胃癌，生殖细胞肿瘤（GCT）和非小细胞肺癌（NSCLC），并且可能与预后不良有关，使CLDN6成为有希望的治疗靶点

Preliminary safety and efficacy results of DS-9606 were reported from the dose escalation part of the phase 1 trial in 53 heavily pretreated patients, including 19 with ovarian, 11 with GCT, seven with gastric/esophageal, seven with NSCLC, five with pancreatic, two with breast and two with endometrial cancer.

DS-9606的初步安全性和有效性结果来自53名经过严重预处理的患者的1期试验的剂量递增部分，包括19名卵巢癌患者，11名GCT患者，7名胃/食管癌患者，7名非小细胞肺癌患者，5名胰腺癌患者，2名乳腺癌患者和2名子宫内膜癌患者。

Patients received a median of four prior therapies (range, 1- 9)..

患者接受了四种先前治疗的中位数（范围1-9）。。

The safety and tolerability of DS-9606 were evaluated at increasing dose levels from 0.016 mg/kg to 0.225 mg/kg with no dose-limiting toxicities observed and no treatment withdrawals due to treatment-related adverse events. The most common treatment emergent adverse events (TEAEs) of any grade in ≥7.5% of patients were nausea (18.9%), fatigue (18.9%), anemia (17.0%), abdominal pain (15.1%), constipation (13.2%), vomiting (13.2%), diarrhea (11.3%), pyrexia (9.4%), weight loss (9.4%), decreased appetite (9.4%), arthralgia (9.4%), cough (9.4%), sinusitis (7.5%), dyspnea (7.5%) and pleural effusion (7.5%).

在从0.016 mg/kg增加到0.225 mg/kg的剂量水平下评估DS-9606的安全性和耐受性，未观察到剂量限制性毒性，也未因治疗相关不良事件而停止治疗。在≥7.5%的患者中，任何级别最常见的治疗紧急不良事件（TEAE）为恶心（18.9%），疲劳（18.9%），贫血（17.0%），腹痛（15.1%），便秘（13.2%），呕吐（13.2%），腹泻（11.3%），发热（9.4%），体重减轻（9.4%），食欲下降（9.4%），关节痛（9.4%），咳嗽（9.4%），鼻窦炎（7.5%），呼吸困难（7.5%）和胸腔积液（7.5%）。

Grade 3 or higher TEAEs occurred in 30.2% of patients (n=16) and included anemia (3.8%), abdominal pain (3.8%), pleural effusion (3.8%), constipation (1.9%), vomiting (1.9%) and diarrhea (1.9%). When grouped, skin-associated events (17%) were also identified as common TEAEs with the majority being grade 1 except for one grade 2 (skin hyperpigmentation) and one grade 3 (rash) event, which resulted in a dose reduction for each patient..

30.2%的患者（n=16）发生3级或更高的TEAE，包括贫血（3.8%），腹痛（3.8%），胸腔积液（3.8%），便秘（1.9%），呕吐（1.9%）和腹泻（1.9%）。分组时，与皮肤相关的事件（17%）也被确定为常见的TEAE，除1级（皮肤色素沉着过度）和1级（皮疹）事件外，大多数为1级，这导致每位患者的剂量减少。。

Preliminary efficacy results were observed in doses greater than or equal to 0.072 mg/kg (except 0.190 mg/kg due to immature data) and included four confirmed objective responses including two responses observed in patients with GCT and one response each in patients with gastric/esophageal cancer and NSCLC.

。

Of seven evaluable patients with GCT, the two patients with confirmed objective response remained on treatment for more than six months and five had a greater than or equal to 90% reduction in alpha-fetoprotein and human chorionic gonadotropin tumor markers. Twenty one of the 53 patients are still receiving treatment with DS-9606 as of data cutoff of June 14, 2024..

在7名可评估的GCT患者中，2名确诊客观反应的患者仍在接受治疗超过6个月，其中5名甲胎蛋白和人绒毛膜促性腺激素肿瘤标志物降低了90%以上。截至2024年6月14日的数据截止日期，53名患者中有21名仍在接受DS-9606治疗。。

“These initial results of DS-9606 are encouraging, particularly those observed in germ cell tumors which are known to express CLDN6 and where the majority of patients experienced a reduction in tumor markers,” said Manish R. Patel, MD, Director of Drug Development, Florida Cancer Specialists and Sarah Cannon Research Institute.

。

“Enrollment continues into the study in order to determine the recommended dose for expansion and better understand how advanced solid tumors may respond to DS-9606.”.

“为了确定扩张的推荐剂量，并更好地了解晚期实体瘤对DS-9606的反应，研究人员继续进行研究。”。

“While these results provide preliminary proof-of-concept for DS-9606, further clinical evaluation is warranted across different tumor types that are known to express CLDN6,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We continue to apply our science and technology expertise to DS-9606, which has been developed from our second antibody drug conjugate platform in order to create potentially new and innovative treatments for certain patients with cancer.”.

“虽然这些结果为DS-9606提供了初步的概念证明，但有必要对已知表达CLDN6的不同肿瘤类型进行进一步的临床评估，”第一三共研发全球负责人Ken Takeshita医学博士说。“我们继续将我们的科学技术专业知识应用于DS-9606，DS-9606是从我们的第二抗体-药物偶联物平台开发的，旨在为某些癌症患者创造潜在的新的创新治疗方法。”。

About the Phase 1 Trial

关于第一阶段试验

The multicenter, open-label, first-in-human phase 1 trial is evaluating the safety, tolerability and efficacy of DS-9606 in adult patients with advanced solid tumors that are known to express CLDN6.

这项多中心，开放标签，首次人体1期试验正在评估DS-9606在已知表达CLDN6的晚期实体瘤成年患者中的安全性，耐受性和有效性。

The dose escalation part of the study is assessing the safety and tolerability of increasing doses of DS-9606 to determine the maximum tolerated dose and/or the recommended dose for expansion. Dose expansion will follow to further evaluate the safety and tolerability as well as efficacy of DS-9606 at the recommended dose in patients with advanced solid tumors in cohorts that will be determined based on data obtained in dose escalation..

该研究的剂量递增部分是评估增加剂量的DS-9606的安全性和耐受性，以确定最大耐受剂量和/或推荐的扩展剂量。随后将扩大剂量，以进一步评估DS-9606在推荐剂量下对晚期实体瘤患者的安全性和耐受性以及疗效，该剂量将根据剂量递增中获得的数据确定。。

The study will evaluate safety and efficacy endpoints, including objective response rate, duration of response and progression-free survival per investigator assessment. Pharmacokinetic and immunogenicity endpoints will also be evaluated.

该研究将评估安全性和有效性终点，包括客观缓解率，缓解持续时间和每个研究者评估的无进展生存期。还将评估药代动力学和免疫原性终点。

The phase 1 trial is currently enrolling patients in Europe and North America. For more information, please visit ClinicalTrials.gov.

第一阶段试验目前正在欧洲和北美招募患者。有关更多信息，请访问ClinicalTrials.gov。

About Claudin-6 (CLDN6)

关于Claudin-6（CLDN6）

Claudin-6 (CLDN6), a member of the claudin family, is a gene that encodes a protein that plays an important role in cell production and differentiation.7,8 CLDN6 is expressed in several tumor types including endometrial, ovarian and gastric cancers, GCT and NSCLC, and can be associated with poor prognosis, making CLDN6 a promising therapeutic target.1-6.

Claudin-6（CLDN6）是Claudin家族的成员，是一种编码在细胞产生和分化中起重要作用的蛋白质的基因[7,8]。CLDN6在几种肿瘤类型中表达，包括子宫内膜癌，卵巢癌和胃癌，GCT和NSCLC，可能与预后不良有关，使CLDN6成为一种有前景的治疗靶点。

About DS-9606

关于DS-9606

DS-9606 is an investigational CLDN6 directed, modified PBD ADC. Designed using Daiichi Sankyo’s second ADC technology platform, DS-9606 consists of a humanized CLDN6 monoclonal antibody, developed in collaboration with Tokyo University of Pharmacy and Life Sciences, attached to a modified PBD payload.

DS-9606是一种研究性CLDN6指导的改良PBD ADC。DS-9606使用Daiichi Sankyo的第二个ADC技术平台设计，由人源化CLDN6单克隆抗体组成，该抗体是与东京药物学和生命科学大学合作开发的，连接到改良的PBD有效载荷上。

DS-9606 is being evaluated in a phase 1 clinical trial in several advanced solid tumors that are known to express CLDN6..

DS-9606正在一项1期临床试验中对几种已知表达CLDN6的晚期实体瘤进行评估。。

About the ADC Portfolio of Daiichi Sankyo

关于第一三共的ADC投资组合

The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.

Daiichi Sankyo ADC组合由七个临床开发中的ADC组成，这些ADC由Daiichi Sankyo内部发现的两个不同的ADC技术平台精心打造而成。

The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca.

临床开发中最深入的ADC平台是Daiichi Sankyo的DXd ADC技术，其中每个ADC由单克隆抗体组成，通过基于四肽的可切割接头连接到许多拓扑异构酶I抑制剂有效载荷（exatecan衍生物，DXd）。DXd ADC投资组合目前由ENHERTU（一种HER2导向的ADC）和datopotamab deruxtecan（Dato DXd）（一种TROP2导向的ADC）组成，它们正在与阿斯利康（AstraZeneca）联合开发并在全球商业化。

Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo..

Patritumab deruxtecan（HER3 DXd），一种HER3导向的ADC，ifinatamab deruxtecan（I-DXd），一种B7-H3导向的ADC，以及raludotatug deruxtecan（R-DXd），一种CDH6导向的ADC，正在与默克公司联合开发和全球商业化。DS-3939是一种TA-MUC1定向的ADC，由Daiichi Sankyo开发。。

The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified PBD payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.

第二个Daiichi Sankyo ADC平台由连接到修饰的PBD有效载荷的单克隆抗体组成。DS-9606是一种CLDN6定向的PBD ADC，是利用该平台进行临床开发的几个计划ADC中的第一个。

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

Datopotamab deruxtecan，ifinatamab deruxtecan，patritumab deruxtecan，raludotatug deruxtecan，DS-3939和DS-9606是尚未在任何国家批准用于任何适应症的研究药物。安全性和有效性尚未确定。

About Daiichi Sankyo

关于第一三共

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs.

Daiichi Sankyo是一家创新的全球医疗保健公司，致力于社会的可持续发展，发现、开发和提供新的护理标准，以丰富世界各地的生活质量。凭借120多年的经验，第一三共利用其世界一流的科学技术，为癌症，心血管疾病和其他医疗需求未得到满足的疾病患者创造新的模式和创新药物。

For more information, please visit www.daiichisankyo.com..

欲了解更多信息，请访问www.daiichisankyo.com。。

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