– The addition of nivolumab to low dose tivozanib after prior immune checkpoint inhibitor (ICI) is not superior to standard dose tivozanib alone; as a result, the primary endpoint was not met –

–在先前的免疫检查点抑制剂（ICI）后，将nivolumab添加到低剂量tivozanib中并不优于单独的标准剂量tivozanib；因此，主要终点没有得到满足——

–  Tivozanib monotherapy (control arm) results provide clinically meaningful efficacy and safety data following front-line ICI combinations –

–Tivozanib单一疗法（对照组）的结果提供了一线ICI组合后具有临床意义的疗效和安全性数据–

–  Safety results reinforce tivozanib is well-tolerated –

–安全性结果强化了tivozanib的耐受性–

–  Data to be submitted to upcoming scientific meeting –

–将提交给即将召开的科学会议的数据–

BOSTON, July 18, 2024 /PRNewswire/ -- AVEO Oncology, an LG Chem company ('AVEO'), announced today that the TiNivo-2 Phase 3 clinical trial in patients with advanced metastatic renal cell carcinoma (RCC) whose tumors had progressed following prior immune checkpoint inhibitor (ICI) treatment did not meet the primary endpoint of increasing progression free survival (PFS) when nivolumab was added to low dose (0.89 mg) FOTIVDA® (tivozanib).

波士顿，2024年7月18日/PRNewswire/--LG化学公司（“AVEO”）AVEO Oncology今天宣布，TiNivo-2 3期临床试验针对晚期转移性肾细胞癌（RCC）患者，其肿瘤在先前的免疫检查点抑制剂（ICI）治疗后进展，当nivolumab加入低剂量（0.89 mg）FOTIVDA®（tivozanib）时，未达到增加无进展生存期（PFS）的主要终点。

Importantly, the clinical trial's control arm using FOTIVDA as monotherapy at the standard dose (1.34 mg) demonstrated a clinically meaningful outcome in median PFS in the second-line following ICI combination therapy. These results build on the prior ICI dataset from the TIVO-3 clinical trial, FOTIVDA's pivotal phase 3 study, and further support the approved use of FOTIVDA as a safe and effective treatment option in relapsed or refractory advanced RCC following two or more prior systemic therapies..

重要的是，使用FOTIVDA作为标准剂量（1.34 mg）的单药治疗的临床试验对照组在ICI联合治疗后的二线中位PFS中显示出临床上有意义的结果。这些结果建立在TIVO-3临床试验（FOTIVDA的关键3期研究）的先前ICI数据集的基础上，并进一步支持在两种或两种以上先前的全身治疗后，FOTIVDA被批准用于复发或难治性晚期RCC的安全有效治疗选择。。

The results from the TiNivo-2 clinical trial are consistent with other recent RCC phase 3 trials in a similar patient population, making this the second phase 3 clinical trial to suggest that there is no clinical benefit derived from rechallenging RCC patients with immunotherapy after receiving ICI beyond progression on previous ICIs..

TiNivo-2临床试验的结果与最近在类似患者人群中进行的其他RCC 3期临床试验一致，这使其成为第二个3期临床试验，表明在接受ICI治疗后，用免疫疗法再次挑战RCC患者不会产生临床益处，超过先前ICI的进展。。

'The PFS and safety of the FOTIVDA control arm in the second-line following ICI combinations adds to the growing body of evidence of the importance of a highly selective anti-VEGFR TKI therapy as an effective, well-tolerated treatment option for relapsed or refractory RCC patients treated with prior ICI combination therapy,' says Michael P.

“在ICI联合治疗后，FOTIVDA对照组在二线治疗中的PFS和安全性增加了越来越多的证据，证明高选择性抗VEGFR TKI治疗对于复发或难治性RCC患者是一种有效的，耐受性良好的治疗选择，”Michael P说。

Bailey, AVEO Oncology Chief Executive Officer and President. 'While the addition of an ICI to low dose FOTIVDA did not improve PFS outcomes after prior ICI, we consider the control arm data an important, evidence-based and clinically meaningful contribution to the oncology community treating relapsed or refractory advanced RCC following front-line ICI combinations.'.

AVEO肿瘤学首席执行官兼总裁贝利（Bailey）虽然在低剂量FOTIVDA中添加ICI并不能改善先前ICI后的PFS结果，但我们认为对照组数据是对一线ICI组合后治疗复发或难治性晚期RCC的肿瘤学界的重要，循证和临床有意义的贡献。

Toni Choueiri, M.D., Director of the Lank Center for Genitourinary Oncology, Director of the Kidney Cancer Center at Dana-Farber Cancer Institute, Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School, and lead investigator comments, 'The PFS and safety results from the control arm support tivozanib as an effective and well-tolerated treatment option in the second-line following an ICI combination as prior systemic therapy.'.

Toni Choueiri，医学博士，Lank泌尿生殖系统肿瘤中心主任，Dana-Farber癌症研究所肾癌中心主任，Jerome和Nancy Kohlberg主席，哈佛医学院医学教授，首席研究员评论道，“控制臂的PFS和安全性结果支持tivozanib作为ICI联合治疗之前的全身治疗后的二线有效且耐受性良好的治疗选择。”。

The TiNivo-2 clinical trial was designed to evaluate the benefit of adding nivolumab, a PD-1 checkpoint inhibitor, to low dose FOTIVDA versus standard dose FOTIVDA in the second-line following ICI combinations or the third-line setting following prior ICI. The TiNivo-2 clinical trial enrolled patients across clinical sites in North America, Latin America, and Europe.

TiNivo-2临床试验旨在评估在ICI组合后的二线或先前ICI后的三线设置中，在低剂量FOTIVDA与标准剂量FOTIVDA中添加nivolumab（一种PD-1检查点抑制剂）的益处。TiNivo-2临床试验在北美，拉丁美洲和欧洲的临床地点招募了患者。

Patients with RCC who progressed after receiving immunotherapy were randomized to either tivozanib single agent or in combination with nivolumab. The trial's primary outcome was progression free survival; secondary endpoints included overall survival, overall response rate, duration of response, and safety..

接受免疫治疗后进展的RCC患者被随机分配到tivozanib单药或与nivolumab联合治疗。该试验的主要结果是无进展生存期；次要终点包括总生存率，总有效率，反应持续时间和安全性。。

Detailed findings are expected to be presented at an upcoming medical meeting.

预计将在即将举行的医学会议上介绍详细的发现。

TiNivo-2 Clinical Trial DetailsPhase 3 clinical trial designed to evaluate the safety and efficacy of tivozanib in combination with nivolumab, as compared to tivozanib as a monotherapy, in RCC patients whose tumors have progressed following prior immune checkpoint inhibitor therapy, known as the TiNivo-2 trial..

TiNivo-2临床试验细节第3阶段临床试验旨在评估替沃扎尼联合nivolumab作为单一疗法与替沃扎尼相比的安全性和有效性，用于先前免疫检查点抑制剂治疗后肿瘤进展的RCC患者，称为TiNivo-2试验。。

About FOTIVDA® (tivozanib) FOTIVDA® (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S.

关于FOTIVDA®（tivozanib）FOTIVDA®（tivozanib）是一种口服的下一代血管内皮生长因子受体（VEGFR）酪氨酸激酶抑制剂（TKI）。它是VEGFR 1,2和3的有效选择性抑制剂，半衰期长，旨在提高疗效和耐受性。AVEO获得美国。

Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021, for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies, based on data from the TIVO-3 trial comparing FOTIVDA to sorafenib. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner Recordati UK Ltd.

食品和药物管理局（FDA）于2021年3月10日批准FOTIVDA，用于治疗两种或两种以上先前全身治疗后复发或难治性晚期肾细胞癌（RCC）的成年患者，基于TIVO-3试验的数据比较FOTIVDA与索拉非尼。FOTIVDA于2017年8月在其合作伙伴Recordati UK Ltd的欧盟和其他国家获得批准。

for the treatment of adult patients with advanced RCC. FOTIVDA was discovered by Kyowa Kirin..

用于治疗晚期RCC的成年患者。FOTIVDA是由Kyowa Kirin发现的。。

IMPORTANT SAFETY INFORMATIONWARNINGS AND PRECAUTION

重要安全信息警告和注意事项

Hypertension and Hypertensive Crisis: Hypertension was reported in 45% of FOTIVDA-treated patients with 22% of the events ≥Grade 3. Hypertensive crises were reported in 0.8% of patients. Do not initiate FOTIVDA in patients with uncontrolled hypertension. Monitor for hypertension and treat as needed.

高血压和高血压危象：45%的FOTIVDA治疗患者报告有高血压，22%的事件≥3级。0.8%的患者报告有高血压危象。不要在未控制的高血压患者中启动FOTIVDA。监测高血压并根据需要进行治疗。

Reduce the FOTIVDA dose for persistent hypertension not controlled by anti-hypertensive medications. Discontinue FOTIVDA for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis..

减少不受抗高血压药物控制的持续性高血压的FOTIVDA剂量。对于无法通过抗高血压治疗控制的严重高血压或高血压危象，停止使用福替达。。

Cardiac Failure: Cardiac failures were reported in 1.6% of FOTIVDA-treated patients, with 1% of events reported as ≥Grade 3; 0.6% of events were fatal. Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA. Manage with dose interruption, dose reduction, or discontinuation..

心力衰竭：1.6%的FOTIVDA治疗患者报告有心力衰竭，1%的事件报告为≥3级；0.6%的事件是致命的。。管理剂量中断、剂量减少或停药。。

Cardiac Ischemia and Arterial Thromboembolic Events: Cardiac ischemia in FOTIVDA-treated patients were reported in 3.2%; 0.4% of events were fatal. Arterial thromboembolic events were reported in 2.0% of FOTIVDA-treated patients, including death due to ischemic stroke (0.1%). Closely monitor patients who are at risk for, or who have a history of these events.

心脏缺血和动脉血栓栓塞事件：FOTIVDA治疗患者的心脏缺血报告率为3.2%；0.4%的事件是致命的。据报道，2.0%的FOTIVDA治疗患者发生动脉血栓栓塞事件，包括缺血性卒中死亡（0.1%）。密切监测有这些事件风险或有这些事件史的患者。

Discontinue FOTIVDA in patients who develop severe arterial thromboembolic events, such as myocardial infarction and stroke..

对于发生严重动脉血栓栓塞事件（如心肌梗塞和中风）的患者，停止服用福替达。。

Venous Thrombotic Events: Venous thromboembolic events were reported in 2.4% of FOTIVDA-treated patients, including 0.3% fatal events. Closely monitor patients who are at increased risk for these events. Discontinue FOTIVDA in patients who develop serious venous thromboembolic events.

静脉血栓事件：2.4%的FOTIVDA治疗患者报告了静脉血栓栓塞事件，包括0.3%的致命事件。密切监测这些事件风险增加的患者。对于发生严重静脉血栓栓塞事件的患者，停止使用福替达。

Hemorrhagic Events: Hemorrhagic events were reported in 11% of FOTIVDA-treated patients; 0.2% of events were fatal. FOTIVDA should be used with caution in patients who are at risk for or who have a history of bleeding.

出血事件：11%的FOTIVDA治疗患者报告出血事件；0.2%的事件是致命的。对于有出血风险或有出血史的患者，应谨慎使用FOTIVDA。

Proteinuria: Proteinuria was reported in 8% of FOTIVDA-treated patients, with 2% Grade 3. Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or interrupt treatment with FOTIVDA. Discontinue FOTIVDA in patients who develop nephrotic syndrome.

蛋白尿：据报道，接受FOTIVDA治疗的患者中有8%患有蛋白尿，其中2%为3级。用FOTIVDA监测整个治疗过程。对于中度至重度蛋白尿，减少剂量或中断FOTIVDA治疗。。

Thyroid Dysfunction: Thyroid dysfunction events were reported in 11% of FOTIVDA-treated patients, with 0.3% of events reported as ≥Grade 3. Monitor thyroid function before initiation and throughout treatment with FOTIVDA.

甲状腺功能障碍：11%的FOTIVDA治疗患者报告了甲状腺功能障碍事件，其中0.3%的事件报告为≥3级。在开始使用FOTIVDA之前和整个治疗过程中监测甲状腺功能。

Wound Healing Complications: Withhold FOTIVDA for at least 24 days prior to elective surgery. Do not administer FOTIVDA for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established..

伤口愈合并发症：在选择性手术前至少24天停止FOTIVDA。大手术后至少2周内不要服用FOTIVDA，直到观察到足够的伤口愈合。伤口愈合并发症解决后恢复FOTIVDA的安全性尚未确定。。

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by MRI, can occur with FOTIVDA. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue FOTIVDA if signs or symptoms of RPLS occur..

可逆性后部白质脑病综合征（RPLS）：RPLS是一种通过MRI诊断的皮质下血管源性水肿综合征，可与FOTIVDA发生。评估癫痫发作，头痛，视觉障碍，困惑或精神功能改变的患者的RPLS。如果出现RPLS的体征或症状，请停止使用FOTIVDA。。

Embryo-fetal Toxicity: FOTIVDA can cause fetal harm. Advise patients of the potential risk to a fetus, to avoid becoming pregnant and to use contraception during treatment and for one month after the last dose of FOTIVDA. Advise males with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose of FOTIVDA..

胚胎-胎儿毒性：福维达可引起胎儿伤害。建议患者注意对胎儿的潜在风险，避免怀孕，并在治疗期间和最后一剂福维达后一个月内使用避孕药。建议有生殖潜力的女性伴侣的男性在治疗期间和最后一剂福提达后一个月内使用有效的避孕措施。。

Allergic Reaction to Tartrazine: FOTIVDA 0.89 mg capsule contains FD&C Yellow No. 5 (tartrazine) as an imprint ink which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

对柠檬黄的过敏反应：FOTIVDA 0.89 mg胶囊含有FD＆C黄色5号（柠檬黄）作为印迹墨水，可能在某些易感患者中引起过敏性反应（包括支气管哮喘）。

ADVERSE REACTIONS

不良反应

The most commonly reported (≥20%) adverse reactions were: fatigue/asthenia, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. Serious adverse reactions reported in >2% of patients included bleeding (3.5%), venous thromboembolism (3.5%), arterial thromboembolism (2.9%), acute kidney injury (2.3%), and hepatobiliary disorders (2.3%)..

最常见的不良反应（≥20%）是：疲劳/虚弱，高血压，腹泻，食欲下降，恶心，发音困难，甲状腺功能减退，咳嗽和口腔炎。超过2%的患者报告的严重不良反应包括出血（3.5%），静脉血栓栓塞（3.5%），动脉血栓栓塞（2.9%），急性肾损伤（2.3%）和肝胆疾病（2.3%）。。

DRUG INTERACTIONS

药物相互作用

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

强CYP3A4诱导剂：避免将FOTIVDA与强CYP3A4诱导剂共同给药。

USE IN SPECIFIC POPULATIONS

在特定人群中使用

Lactation: Advise women not to breastfeed during FOTIVDA treatment and for at least 1 month after the last dose.

哺乳期：建议女性在服用福维达期间以及服用最后一剂后至少1个月内不要母乳喂养。

Renal Impairment: The recommended dosage for patients with end-stage renal disease has not been established.

肾功能不全：尚未确定终末期肾病患者的推荐剂量。

Hepatic Impairment: Reduce the FOTIVDA dose for patients with moderate hepatic impairment. The recommended dosage in patients with severe hepatic impairment has not been established.

肝功能损害：减少中度肝功能损害患者的FOTIVDA剂量。严重肝功能损害患者的推荐剂量尚未确定。

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

要报告疑似不良反应，请联系AVEO Pharmaceuticals，Inc.，电话1-833-FOTIVDA（1-833-368-4832），或联系FDA，电话1-800-FDA-1088或www.FDA.gov/medwatch。

Please see full Prescribing Information for FOTIVDA® (tivozanib).

请参阅FOTIVDA®（tivozanib）的完整处方信息。

About AVEO Pharmaceuticals, Inc.AVEO is an oncology-focused biopharmaceutical company committed to delivering medicines that provide a better life for patients with cancer. AVEO currently markets FOTIVDA® (tivozanib) in the U.S. for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

关于AVEO Pharmaceuticals，Inc.AVEO是一家专注于肿瘤学的生物制药公司，致力于为癌症患者提供更好生活的药物。AVEO目前在美国销售FOTIVDA®（tivozanib），用于治疗两种或两种以上先前全身治疗后复发或难治性晚期肾细胞癌（RCC）的成年患者。

AVEO continues to develop FOTIVDA in immuno-oncology and other novel targeted combinations in RCC and other indications, and has other investigational programs in clinical development. AVEO became a wholly owned subsidiary of LG Chem Life Sciences USA, Inc. on January 19, 2023. AVEO continues to operate under the AVEO Oncology, an LG Chem company, name..

AVEO继续在免疫肿瘤学和RCC和其他适应症中的其他新型靶向组合中开发FOTIVDA，并在临床开发中拥有其他研究计划。2023年1月19日，AVEO成为LG Chem Life Sciences USA，Inc.的全资子公司。AVEO继续在LG化学公司AVEO Oncology旗下运营。。

About LG Chem, Ltd. and LG Chem Life SciencesLG Chem, Ltd. (LG Chem) is a leading global chemical company with a diversified business portfolio in the key areas of petrochemicals, advanced materials, and life sciences. The company manufactures a wide range of products from high-value added petrochemicals to renewable plastics, specializing in cutting-edge electronic and battery materials, as well as drugs and vaccines to deliver differentiated solutions for its customers.

关于LG Chem，Ltd.和LG Chem Life sciences LG Chem，Ltd.（LG Chem）是一家领先的全球化工公司，在石化、先进材料和生命科学等关键领域拥有多元化的业务组合。该公司生产多种产品，从高附加值的石化产品到可再生塑料，专门生产尖端电子和电池材料，以及药物和疫苗，为客户提供差异化的解决方案。

LG Chem Life Sciences develops, manufactures, and globally commercializes pharmaceutical products, with a focus on Oncology, Immunology, and Metabolic diseases. Our mission is to transform people's lives through inspiring science and leading innovation. For more information, please visit www.lgchem.com..

LG Chem Life Sciences开发、制造和全球商业化医药产品，重点关注肿瘤学、免疫学和代谢疾病。我们的使命是通过激励科学和领导创新来改变人们的生活。有关更多信息，请访问www.lgchem.com。。

References

参考文献

ClinicalTrials.gov. Study to Compare Tivozanib in Combination with Nivolumab to Tivozanib Monotherapy in Subjects with Renal Cell Carcinoma. Accessed July 12, 2024. https://clinicaltrials.gov/ct2/show/NCT04987203

ClinicalTrials.gov。一项比较替沃扎尼联合Nivolumab与替沃扎尼单药治疗肾细胞癌患者的研究。2024年7月12日访问。https://clinicaltrials.gov/ct2/show/NCT04987203

FOTIVDA (tivozanib)[https://www.fotivda.com/fotivdapi.pdf].Boston, MA: AVEO Pharmaceuticals, Inc.

FOTIVDA（替沃扎尼）[https://www.fotivda.com/fotivdapi.pdf].马萨诸塞州波士顿：AVEO Pharmaceuticals，股份有限公司。

OPDIVO (nivolumab)[https://packageinserts.bms.com/pi/pi_opdivo.pdf ].Princeton, NJ: Bristol-Myers Squibb Company.

OPDIVO（纳武单抗）[https://packageinserts.bms.com/pi/pi_opdivo.pdf].新泽西州普林斯顿：百时美施贵宝公司。

Contacts

联系人

Media:John F. KoutenJFK Communications, Inc.jfkouten@jfkhealth.com (908) 227-4714

媒体：John F.KoutenJFK Communications，Inc.jfkouten@jfkhealth.com（908）227-4714

SOURCE AVEO, an LG Chem company

来源：乐金化学公司AVEO