Osaka, Japan, July 11, 2025 - Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President and COO: Toichi Takino; “Ono”) today announced that Ono Pharma Korea Co., Ltd. (“OPKR”), a Korean subsidiary of Ono, received the additional approval of Opdivo® (nivolumab) Intravenous Infusion ('Opdivo'), an anti-PD-1 antibody, on July 10 from the Ministry of Food and Drug Safety (MFDS) in South Korea, for the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma..

日本大阪，2025年7月11日——小野药品工业株式会社（总部：日本大阪；总裁兼首席运营官：武野贵一；“小野”）今日宣布，其韩国子公司小野制药韩国公司（“OPKR”）于7月10日获得韩国食品药品安全部（MFDS）批准追加使用Opdivo®（纳武利尤单抗）静脉注射剂（“Opdivo”），一种抗PD-1抗体，用于一线治疗无法切除或转移性肝细胞癌患者。

This approval is based on the results from the CheckMate -9DW study, a global multi-center Phase 3 clinical study (CA209-9DW: ONO-4538-92), evaluating Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy for patients with unresectable HCC who have not received prior systemic anti-cancer therapy.

该批准基于 CheckMate -9DW 研究的结果，这是一项全球多中心的 III 期临床研究（CA209-9DW：ONO-4538-92），评估了 Opdivo 联合 Yervoy 与研究者选择的仑伐替尼或索拉非尼单药治疗相比，用于未接受过先前系统性抗癌治疗的不可切除肝细胞癌（HCC）患者的效果。

In this study, in which 85% of patients in the comparator arm were treated with lenvatinib and 15% were treated with sorafenib, Opdivo plus Yervoy met its primary endpoint of overall survival (OS), demonstrating a statistically significant and clinically meaningful improvement in OS compared to lenvatinib or sorafenib monotherapy.

在这项研究中，对照组85%的患者接受仑伐替尼治疗，15%的患者接受索拉非尼治疗，Opdivo联合Yervoy达到了其总生存期（OS）的主要终点，与仑伐替尼或索拉非尼单药治疗相比，显示出在OS上的统计学显著性和临床意义的改善。

The median OS with Opdivo plus Yervoy (n=335) was 23.7 months (95% CI: 18.8-29.4) vs. 20.6 months (95% CI: 17.5-22.5) with lenvatinib or sorafenib (n=333; HR=0.79; 95% CI: 0.65-0.96 P=0.018), reducing the risk of death by 21%..

Opdivo联合Yervoy组（n=335）的中位OS为23.7个月（95% CI：18.8-29.4），而仑伐替尼或索拉非尼组（n=333）为20.6个月（95% CI：17.5-22.5；HR=0.79；95% CI：0.65-0.96，P=0.018），死亡风险降低了21%。

The safety profile of Opdivo plus Yervoy was consistent with previously reported data, with no new safety signals identified.

Opdivo联合Yervoy的安全性与之前报告的数据一致，未发现新的安全性信号。

About CheckMate -9DW Study (CA209-9DW: ONO-4538-92)

关于CheckMate -9DW研究（CA209-9DW：ONO-4538-92）

CheckMate -9DW study is a global multicenter randomized open-label Phase 3 study evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy in patients with advanced hepatocellular carcinoma who have not received prior systemic anti-cancer therapy..

CheckMate -9DW 研究是一项全球多中心随机开放标签的 3 期研究，评估 Opdivo 联合 Yervoy 与研究者选择的仑伐替尼或索拉非尼单药治疗在未接受过先前系统性抗癌治疗的晚期肝细胞癌患者中的效果。

668 patients were randomized to receive Opdivo plus Yervoy (Opdivo 1 mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480 mg Q4W) infusion, or single agent lenvatinib or sorafenib as oral capsules in the control arm (335 patients in the Opdivo and Yervoy combination therapy arm, 333 patients in the control arm).

668名患者被随机分配接受Opdivo加Yervoy（Opdivo 1 mg/kg 加 Yervoy 3 mg/kg 每三周一次，最多四剂，随后进行Opdivo单药治疗480 mg 每四周一次）静脉注射，或在对照组中接受单药Lenvatinib或Sorafenib口服胶囊（335名患者在Opdivo和Yervoy联合治疗组，333名患者在对照组）。

The primary endpoint of the study is OS and key secondary endpoints include objective response rate (ORR), duration of response (DOR) and time to symptom deterioration (TTSD)..

研究的主要终点是总生存期（OS），关键的次要终点包括客观缓解率（ORR）、缓解持续时间（DOR）和症状恶化时间（TTSD）。

About Hepatocellular Carcinoma

关于肝细胞癌

Liver cancer is the third most frequent cause of cancer death worldwide. It is estimated that there were approximately 866,000 new cases of liver cancer worldwide in 2022, with an estimated approximately 758,000 deaths

肝癌是全球第三大癌症死亡原因。据估计，2022年全球新增肝癌病例约为866,000例，估计约有758,000人死亡。

. In South Korea, it is estimated that there were approximately 15,000 new cases of liver cancer in 2022, with an estimated approximately 13,000 deaths

在韩国，2022年估计有约15,000例新发肝癌病例，估计约有13,000人死亡。

. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for 90% of all liver cancers

肝细胞癌（HCC）是最常见的原发性肝癌类型，占所有肝癌的90%。

. In the past, many cases of HCC developed caused by viral liver disease, such as infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV), but in recent years, the number of cases caused by non-viral liver diseases has been increasing

过去，许多肝细胞癌（HCC）病例是由病毒性肝病引起的，例如乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染，但近年来，由非病毒性肝病引起的病例数量一直在增加。

. With the rise in non-viral liver cancer, HCC is often diagnosed in an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes.

随着非病毒性肝癌的增加，HCC常在晚期被诊断出来，此时有效的治疗选择有限，且通常预后较差。

Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation

在五年内，多达70%的患者会经历复发，尤其是那些在手术或消融后仍被认为处于高风险的患者。

About Opdivo

关于Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response by blocking the interaction between PD-1 and its ligands. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers since the approval for the treatment of melanoma in Japan in July 2014.

Opdivo是一种程序性死亡受体-1（PD-1）免疫检查点抑制剂，旨在通过阻断PD-1与其配体之间的相互作用，独特地利用人体自身的免疫系统来帮助恢复抗肿瘤免疫反应。通过利用人体自身的免疫系统来对抗癌症，自2014年7月在日本获批用于治疗黑色素瘤以来，Opdivo已成为多种癌症的重要治疗选择。

Opdivo is currently approved in more than 65 countries, including Japan, South Korea, Taiwan, the US and European Union..

Opdivo目前已在包括日本、韩国、台湾、美国和欧盟在内的65多个国家获得批准。

In Japan, Ono launched Opdivo for the treatment of unresectable melanoma in September 2014. Thereafter, Opdivo received an approval for additional indications of unresectable advanced or recurrent non-small cell lung cancer in December 2015, unresectable or metastatic renal cell carcinoma in August 2016, relapsed or refractory classical Hodgkin lymphoma in December 2016, recurrent or metastatic head and neck cancer in March 2017, unresectable advanced or recurrent gastric cancer which has progressed after chemotherapy in September 2017, unresectable advanced or recurrent malignant pleural mesothelioma which has progressed after chemotherapy in August 2018, microsatellite instability high (MSI-High) unresectable advanced or recurrent colorectal cancer that has progressed following chemotherapy and unresectable advanced or recurrent esophageal cancer that has progressed following chemotherapy in February 2020, cancer of unknown primary in December 2021, adjuvant treatment of urothelial carcinoma in March 2022, malignant mesothelioma (excluding malignant pleural mesothelioma) in November 2023, unresectable advanced or recurrent malignant epithelial tumors in February 2024, and unresectable urothelial carcinoma in December 2024..

2014年9月，小野药品在日本推出Opdivo用于治疗不可切除的黑色素瘤。此后，Opdivo在2015年12月获得用于不可切除的晚期或复发性非小细胞肺癌的额外适应症批准，2016年8月用于不可切除或转移性肾细胞癌，2016年12月用于复发或难治性经典霍奇金淋巴瘤，2017年3月用于复发或转移性头颈部癌症，2017年9月用于化疗后进展的不可切除的晚期或复发性胃癌，2018年8月用于化疗后进展的不可切除的晚期或复发性恶性胸膜间皮瘤，2020年2月用于微卫星不稳定性高（MSI-High）且化疗后进展的不可切除的晚期或复发性结直肠癌以及化疗后进展的不可切除的晚期或复发性食管癌，2021年12月用于原发不明癌，2022年3月用于尿路上皮癌的辅助治疗，2023年11月用于恶性间皮瘤（不包括恶性胸膜间皮瘤），2024年2月用于不可切除的晚期或复发性恶性上皮肿瘤，并将于2024年12月用于不可切除的尿路上皮癌。

About Yervoy

关于Yervoy

Yervoy is a recombinant, human monoclonal antibody, and binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Yervoy binds to CTLA-4, and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells.

Yervoy是一种重组的人源单克隆抗体，能够与细胞毒性T淋巴细胞相关抗原-4（CTLA-4）结合。CTLA-4是T细胞活化的负调节因子。Yervoy与CTLA-4结合后，可阻断CTLA-4与其配体CD80/CD86的相互作用。研究表明，CTLA-4的阻断可以增强T细胞的活化和增殖，包括肿瘤浸润性效应T细胞的活化和增殖。

Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma.

抑制CTLA-4信号传导还可以降低T调节细胞功能，这可能有助于提高T细胞的总体反应性，包括抗肿瘤免疫反应。2011年3月25日，美国食品药品监督管理局（FDA）批准Yervoy 3 mg/kg单药疗法用于无法手术切除或转移性黑色素瘤患者。

Yervoy is now approved in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. In Japan, Yervoy was approved for the indication of unresectable malignant melanoma in July 2015..

Yervoy目前已在50多个国家获得批准。Yervoy有广泛的、正在进行的开发计划，涵盖多种肿瘤类型。在日本，Yervoy于2015年7月获批用于不可切除的恶性黑色素瘤的治疗。

About the Ono and Bristol Myers Squibb Collaboration

关于小野制药和百时美施贵宝的合作

In 2011, through a collaboration agreement with Bristol Myers Squibb (BMS), Ono granted BMS its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to Opdivo except the US at the time. In July 2014, Ono and BMS further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agent and combination regimens – for patients with cancer in Japan, South Korea and Taiwan..

2011年，通过与百时美施贵宝（BMS）的合作协议，小野药品授予BMS在全球范围内开发和商业化Opdivo的领土权利，但日本、韩国和台湾地区除外，当时小野药品在这些地区保留了除美国外的所有Opdivo权利。2014年7月，小野药品和BMS进一步扩大了双方的战略合作协议，共同开发和商业化多种免疫疗法——包括单药治疗和联合方案——用于日本、韩国和台湾的癌症患者。

About Ono Pharma Korea Co., Ltd.

关于小野制药韩国公司

Ono Pharma Korea Co., Ltd. (Seoul, Korea; “OPKR”) is an Ono’s wholly-owned subsidiary established in December 2013. OPKR has established our own sales organization in South Korea and marketed Opdivo, an anti-PD-1 antibody/anti-neoplastic drug through our own sales organization since 2015. OPKR has been committed to developing and marketing innovative new products to meet unmet medical needs and bring them to patients in South Korea as soon as possible..

韩国小野制药有限公司（韩国首尔；“OPKR”）是小野制药于2013年12月成立的全资子公司。OPKR在韩国建立了自己的销售组织，并自2015年起通过自身的销售团队推广抗PD-1抗体/抗癌药物Opdivo。OPKR一直致力于开发和营销创新的新产品，以满足未被满足的医疗需求，并尽快将这些产品带给韩国的患者。