Osaka, Japan, May 17, 2024 - Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President: Toichi Takino; “Ono”) today announced that it has received supplemental approvals for BRAFTOVI® (generic name: encorafenib) Capsule (“BRAFTOVI”), a BRAF inhibitor, and MEKTOVI® (generic name: binimetinib) Tablet (“MEKTOVI”), a MEK inhibitor, when used in combination, in Japan for the two new indications of “unresectable thyroid cancer with a BRAF mutation that has progressed following chemotherapy”, and “unresectable anaplastic thyroid cancer with a BRAF mutation”..

日本大阪，2024年5月17日-大野制药有限公司（总部：日本大阪；总裁：Toichi Takino；“大野”）今天宣布，它已获得BRAF抑制剂BRAFTOVI®（通用名：encorafenib）胶囊（“BRAFTOVI”）和MEK抑制剂MEKTOVI®（通用名：binimetinib）片剂（“MEKTOVI”）的补充批准，联合使用，用于日本的两种新适应症“化疗后进展的BRAF突变的不可切除甲状腺癌”和“BRAF突变的不可切除的间变性甲状腺癌”。。

These approvals are based on the results of a Phase 2 study (ONO-7702/7703-03), conducted in Japan in 22 patients with unresectable BRAFV600-mutant thyroid cancer, including 5 patients with anaplastic thyroid cancer. The study met its primary endpoint of objective response rate (ORR) as assessed by the Independent Central Review in the overall patient population, which was 54.5% (12/22 cases, 95% confidence interval: 32.2 - 75.6%) in the combination therapy of BRAFTOVI and MEKTOVI.

这些批准是基于在日本对22例不可切除的BRAFV600突变型甲状腺癌患者（包括5例间变性甲状腺癌患者）进行的2期研究（ONO-7702/7703-03）的结果。该研究达到了客观缓解率（ORR）的主要终点，这是由整体患者人群的独立中央评估评估得出的，BRAFTOVI和MEKTOVI联合治疗的客观缓解率为54.5%（12/22例，95%置信区间：32.2-75.6%）。

The safety profile of the combination therapy of BRAFTOVI and MEKTOVI in the study was consistent with those previously reported in the clinical trials of BRAFTOVI and MEKTOVI..

该研究中BRAFTOVI和MEKTOVI联合治疗的安全性与之前在BRAFTOVI和MEKTOVI临床试验中报道的一致。。

About Phase 2 study (ONO-7702/7703-03)

关于第二阶段研究（ONO-7702/7703-03）

The study is a multi-centre, open-label, uncontrolled Phase 2 study (ONO-7702/7703-03), conducted in Japan, evaluating the efficacy and safety of the combination therapy of BRAFTOVI and MEKTOVI in patients with unresectable BRAFV600-mutant thyroid cancer. Patients received the combination therapy with BRAFTOVI 450 mg once daily, and MEKTOVI 45 mg twice daily, until it was determined that treatment could not be given due to disease progression or safety reasons.

该研究是一项在日本进行的多中心，开放标签，不受控制的2期研究（ONO-7702/7703-03），评估了BRAFTOVI和MEKTOVI联合治疗不可切除的BRAFV600突变型甲状腺癌患者的疗效和安全性。患者每天一次接受BRAFTOVI 450 mg的联合治疗，每天两次接受MEKTOVI 45 mg的联合治疗，直到确定由于疾病进展或安全原因无法进行治疗。

The primary endpoint of the study was objective response rate (ORR) as assessed by the Independent Central Review. Secondary endpoints include ORR as assessed by physician of each medical institutes, disease control rate (DCR), overall survival (OS) and progression-free survival (PFS)..

该研究的主要终点是独立中央审查评估的客观缓解率（ORR）。次要终点包括每个医疗机构的医生评估的ORR，疾病控制率（DCR），总生存期（OS）和无进展生存期（PFS）。。

About Thyroid Cancer

关于甲状腺癌

Thyroid cancer (TC) is a malignant tumor that develops in the thyroid tissue located around the trachea or in front of the neck. Histologically, it is roughly divided into differentiated carcinoma (approximately 97% of TC), undifferentiated carcinoma (1 - 2%), and medullary carcinoma (1 - 2%). In Japan, it is estimated that approximately 18,700 new cases are diagnosed with TC per year with approximately 1,900 deaths per year resulting from the disease in 2023*.

甲状腺癌（TC）是一种恶性肿瘤，发生于气管周围或颈部前方的甲状腺组织中。组织学上，它大致分为分化癌（约占TC的97%），未分化癌（1-2%）和髓样癌（1-2%）。在日本，据估计，2023年，每年约有18700例新病例被诊断出患有TC，每年约有1900人死于该疾病*。

BRAF mutation is reported in 37 - 68% of TC patients..

据报道，37%至68%的TC患者存在BRAF突变。。

Cancer Statics in Japan, 2024, The Editorial Board of Cancer Statistics, Foundation for Promotion of Cancer Research (FPCR), March 2024

日本癌症统计，2024年，癌症统计编辑委员会，癌症研究促进基金会（FPCR），2024年3月

Overview of BRAFTOVI® Capsule 50 mg and 75 mg

BRAFTOVI概述® 胶囊50 mg和75 mg

Product Name

产品名称

BRAFTOVI® Capsule 50 mg and 75 mg

布拉夫托维® 胶囊50 mg和75 mg

Generic name (JAN)

通用名称（一月）

Encorafenib

Encorafenib

Indication

指示

Unresectable melanoma with a BRAF mutation

不可切除的BRAF突变黑色素瘤

Unresectable advanced or recurrent colorectal cancer with a BRAF mutation that has progressed following chemotherapy

化疗后进展为BRAF突变的不可切除的晚期或复发性结直肠癌

Unresectable thyroid cancer with a BRAF mutation that has progressed following chemotherapy

化疗后进展为BRAF突变的不可切除甲状腺癌

Unresectable anaplastic thyroid cancer with a BRAF mutation

具有BRAF突变的不可切除的间变性甲状腺癌

Dosage and administration

剂量和给药

<Unresectable melanoma with a BRAF mutation, Unresectable thyroid cancer with a BRAF mutation that has progressed following chemotherapy, Unresectable anaplastic thyroid cancer with a BRAF mutation>

<不可切除的BRAF突变黑色素瘤，化疗后进展的BRAF突变不可切除的甲状腺癌，BRAF突变不可切除的间变性甲状腺癌>

In combination with binimetinib, usually, for adults, administer 450 mg of encorafenib orally once a day. According to patients’ condition, the dose should be reduced.

通常，对于成年人，与binimetinib联合使用，每天一次口服450 mg encorafenib。根据患者的情况，应减少剂量。

<Unresectable advanced or recurrent colorectal cancer with a BRAF mutation that has progressed following chemotherapy>

<化疗后进展为BRAF突变的不可切除的晚期或复发性结直肠癌>

In combination with cetuximab (genetical recombination) or with binimetinib and cetuximab (genetical recombination), usually, for adults, administer 300 mg of encorafenib orally once a day. According to patients’ condition, the dose should be reduced.

与西妥昔单抗（基因重组）或binimetinib和西妥昔单抗（基因重组）联合使用，通常对于成年人，每天一次口服300 mg encorafenib。根据患者的情况，应减少剂量。

Manufacturer/distributor

制造商/分销商

Ono Pharmaceutical Co., Ltd.

大野制药有限公司。

Note: Underlined parts show the revised ones due to this approval.

注：带下划线的部分表示因本次批准而修订的部分。

Overview of MEKTOVI® Tablet 15 mg

MEKTOVI概述® 片剂15 mg

Product Name

产品名称

MEKTOVI® Tablet 15 mg

阿维菌素® 片剂15 mg

Generic name (JAN)

通用名称（一月）

Binimetinib

比尼替尼

Indication

指示

Unresectable melanoma with a BRAF mutation

不可切除的BRAF突变黑色素瘤

Unresectable advanced or recurrent colorectal cancer with a BRAF mutation that has progressed following chemotherapy

化疗后进展为BRAF突变的不可切除的晚期或复发性结直肠癌

Unresectable thyroid cancer with a BRAF mutation that has progressed following chemotherapy

化疗后进展为BRAF突变的不可切除甲状腺癌

Unresectable anaplastic thyroid cancer with a BRAF mutation

具有BRAF突变的不可切除的间变性甲状腺癌

Dosage and administration

剂量和给药

<Unresectable melanoma with a BRAF mutation, Unresectable thyroid cancer with a BRAF mutation that has progressed following chemotherapy, Unresectable anaplastic thyroid cancer with a BRAF mutation>

<不可切除的BRAF突变黑色素瘤，化疗后进展的BRAF突变不可切除的甲状腺癌，BRAF突变不可切除的间变性甲状腺癌>

In combination with encorafenib, usually, for adults, administer 45 mg of encorafenib orally twice a day. According to patients’ condition, the dose should be reduced.

通常，对于成年人，与encorafenib联合使用时，每天两次口服45 mg encorafenib。根据患者的情况，应减少剂量。

<Unresectable advanced or recurrent colorectal cancer with a BRAF mutation that has progressed following chemotherapy>

<化疗后进展为BRAF突变的不可切除的晚期或复发性结直肠癌>

In combination with encorafenib and cetuximab (genetical recombination), usually, for adults, administer 45 mg of binimetinib orally twice a day. According to patients’ condition, the dose should be reduced.

通常，对于成年人，与encorafenib和西妥昔单抗（基因重组）联合使用，每天两次口服45 mg binimetinib。根据患者的情况，应减少剂量。

Manufacturer/distributor

制造商/分销商

Ono Pharmaceutical Co., Ltd.

大野制药有限公司。

Note: Underlined parts show the revised ones due to this approval.

注：带下划线的部分表示因本次批准而修订的部分。

About BRAFTOVI® and MEKTOVI®

关于BRAFT® 和MEKT®

BRAFTOVI is a small molecule BRAF kinase inhibitor and MEKTOVI is a small molecule MEK inhibitor. BRAF and MEK are important protein kinases in the MAPK signalling pathway (RAS-RAF-MEK-ERK), which regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis.

BRAFTOVI是一种小分子BRAF激酶抑制剂，MEKTOVI是一种小分子MEK抑制剂。BRAF和MEK是MAPK信号通路（RAS-RAF-MEK-ERK）中的重要蛋白激酶，其调节几种关键的细胞活性，包括增殖，分化，存活和血管生成。

Inappropriate activation of proteins in this pathway has been shown to occur in many types of cancers including melanoma, colorectal cancer and thyroid cancer. Both BRAFTOVI and MEKTOVI target key enzymes in this pathway. In Japan, Ono received a manufacturing and marketing approval of BRAFTOVI and MEKTOVI for the treatment of unresectable melanoma with a BRAF mutation in combination therapy of the products in January 2019 and launched them in February 2019.

已显示该途径中蛋白质的不适当激活发生在许多类型的癌症中，包括黑色素瘤，结直肠癌和甲状腺癌。BRAFTOVI和MEKTOVI都靶向该途径中的关键酶。 在日本，小野于2019年1月获得了BRAFTOVI和MEKTOVI的生产和销售批准，用于治疗BRAF突变的不可切除黑色素瘤，并于2019年2月推出。

Thereafter, Ono received additional approval in November 2020 for the treatment of unresectable advanced or recurrent colorectal cancer with a BRAF mutation that has progressed following chemotherapy, in triplet combination treatment of BRAFTOVI, MEKTOVI and cetuximab, an anti-human EGFR monoclonal antibody, as well as in doublet combination treatment of BRAFTOVI and cetuximab. Abroad, Array BioPharma Inc.

此后，小野于2020年11月获得额外批准，用于治疗化疗后进展的BRAF突变的不可切除的晚期或复发性结直肠癌，三联疗法治疗BRAFTOVI，MEKTOVI和西妥昔单抗（一种抗人EGFR单克隆抗体），以及BRAFTOVI和西妥昔单抗的双重联合治疗。 在国外，Array BioPharma Inc。

(a wholly owned subsidiary of Pfizer Inc.) and its collaboration partner, Pierre Fabre, received an approval of BRAFTOVI and MEKTOVI for the treatment of unresectable or metastatic melanoma with BRAFV600E or V600K mutation and launched them in 2018 in the US and EU, respectively. Thereafter, the companies received supplemental approval for the treatment of metastatic colorectal cancer with a BRAFV600E mutation following prior therapy in the US and EU in 2020.

（辉瑞公司的全资子公司）及其合作伙伴皮埃尔·法布尔（PierreFabre）获得了布拉夫托维（BRAFTOVI）和梅克托维（MEKTOVI）的批准，用于用BRAFV600E治疗不可切除或转移性黑色素瘤 或 V600K突变，并于2018年分别在美国和欧盟推出。此后，这些公司在2020年之前在美国和欧盟接受治疗后，获得了BRAFV600E突变转移性结直肠癌治疗的补充批准。

Additionally, Pfizer received supplemental approval in the US for the treatment of metastatic non-small cell lung cancer with a BRAFV600E mutation in 2023.

此外，辉瑞公司于2023年在美国获得补充批准，用于治疗具有BRAFV600E突变的转移性非小细胞肺癌。

About the Ono Pharmaceutical Co., Ltd. and Pfizer Inc. Collaboration

关于大野制药有限公司与辉瑞公司的合作

In May 2017, Ono entered into the license agreement with Array BioPharma Inc. (became a subsidiary of Pfizer Inc. as of July 30, 2019) regarding BRAFTOVI (encorafenib), a BRAF inhibitor and MEKTOVI (binimetinib), a MEK inhibitor and received rights to develop and commercialize both products in Japan and South Korea..

2017年5月，小野与Array BioPharma Inc.（截至2019年7月30日成为辉瑞公司的子公司）就BRAF抑制剂BRAFTOVI（encorafenib）和MEK抑制剂MEKTOVI（binimetinib）签订了许可协议，并获得了在日本和韩国开发和商业化这两种产品的权利。。