ALAMEDA, Calif.--(BUSINESS WIRE)--Exelixis, Inc. (Nasdaq: EXEL) today announced detailed final overall survival (OS) results from CONTACT-02, a phase 3 pivotal study evaluating cabozantinib (CABOMETYX®) in combination with atezolizumab (Tecentriq®) compared with a second novel hormonal therapy (NHT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and measurable extra-pelvic soft tissue disease who have progressed on one prior NHT.

加利福尼亚州阿拉米达（商业新闻短讯）--Exelixis，Inc.（纳斯达克：EXEL）今天宣布了CONTACT-02的详细最终总生存期（OS）结果，CONTACT-02是一项评估cabozantinib（CABOMETYX®）联合atezolizumab（Tecentriq®）与第二种新型激素疗法（NHT）治疗转移性去势抵抗性前列腺癌（mCRPC）和可测量的骨盆外软组织疾病患者的3期关键研究，这些患者在之前的NHT中取得了进展。

These data are being presented today at the 2024 European Society for Medical Oncology Congress (ESMO 2024) during the Proffered Paper Session: GU Tumours, Prostate at 2:45 p.m. CEST..

这些数据今天在2024年欧洲肿瘤医学会（ESMO 2024）的论文会议上提交：GU肿瘤，前列腺，CEST下午2:45。。

“Despite recent advancements, outcomes remain poor for patients with metastatic castration-resistant prostate cancer whose disease progresses after novel hormonal therapy – particularly those with liver metastases,” said Neeraj Agarwal, M.D., FASCO, Senior Director for Clinical Research at Huntsman Cancer Institute at the University of Utah and the global lead investigator of the trial.

犹他大学亨茨曼癌症研究所临床研究高级主任、该试验的全球首席研究员、医学博士尼拉吉·阿加瓦尔（Neeraj Agarwal）说：“尽管最近取得了进展，但转移性去势抵抗性前列腺癌患者的预后仍然很差，这些患者的疾病在新的激素治疗后会进展，尤其是那些肝转移的患者。”。

“I believe there is a critical need for novel agents with a new mechanism of action that are broadly accessible to patients and can delay disease progression. The positive results from CONTACT-02, especially in the subset of patients with liver metastasis, reinforce the therapeutic potential of cabozantinib in combination with atezolizumab for these patients.”.

“我认为迫切需要具有新作用机制的新药，这些新药可广泛用于患者，并可延缓疾病进展。CONTACT-02的阳性结果，特别是在肝转移患者亚组中，增强了cabozantinib联合atezolizumab对这些患者的治疗潜力。”。

The two primary endpoints for CONTACT-02 were progression-free survival (PFS) and OS. At a median follow-up of 24.0 months, the final analysis of OS showed a numerical but not statistically significant improvement favoring cabozantinib in combination with atezolizumab (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P=0.296).

CONTACT-02的两个主要终点是无进展生存期（PFS）和OS。在中位随访24.0个月时，OS的最终分析显示，卡博替尼联合atezolizumab有数值但无统计学意义的改善（风险比：0.89；95%置信区间：0.72-1.10；P=0.296）。

An improvement in OS was observed in multiple clinical subgroups, notably in patients with bone or liver metastases, with the latter category representing a population whose disease may be evolving away from androgen receptor signaling. Additional OS efficacy findings are included in Table 1 below..

在多个临床亚组中观察到OS的改善，特别是在骨或肝转移患者中，后一类代表其疾病可能正在远离雄激素受体信号传导的人群。下表1列出了其他OS疗效发现。。

TABLE 1

表1

ITT population

ITT人口

Bone metastases

骨转移癌

Liver metastases

肝转移

Patients, n

患者，n

575

575

446

446

132

132

HR

人力资源

(95% CI)

（95%置信区间）

P-value

P值

0.89

0.89

(0.72, 1.10)

(0.72, 1.10)

P=0.30

P=0.30

0.79

0.79

(0.63, 1.00)

(0.63, 1.00)

P=0.046

P=0.046

0.68

0.68

(0.47, 1.00)

(0.47, 1.00)

P=0.051

P=0.051

Median OS (C+A); months

中位OS（C+A）；个月

14.8

14.8

(13.4, 16.7)

(13.4, 16.7)

13.8

13.8

(11.9, 16.3)

(11.9, 16.3)

12.2

12.2

(8.8, 13.8)

(8.8, 13.8)

Median OS (NHT); months

中位OS（NHT）；个月

15.0

15.0

(13.0, 18.5)

(13.0, 18.5)

11.6

11.6

(10.5, 14.1)

(10.5, 14.1)

7.1

7.1

(5.3, 10.4)

(5.3, 10.4)

C+A: cabozantinib + atezolizumab; CI: confidence interval; HR: hazard ratio; ITT: intent-to-treat; NHT: novel hormonal therapy; OS: overall survival

C+A：cabozantinib+atezolizumab；CI：置信区间；HR：风险比；ITT：意向治疗；NHT：新型激素疗法；OS：总体生存

“Within the current treatment landscape, there is a growing population of patients with metastatic castration-resistant prostate cancer with extra-pelvic soft tissue metastases whose disease has progressed after novel hormonal therapy, leaving a high unmet need for effective, widely available treatments for these patients,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis.

“在目前的治疗环境中，越来越多的转移性去势抵抗性前列腺癌患者伴有盆腔外软组织转移，其疾病在新型激素治疗后有所进展，对这些患者的有效，广泛可用的治疗需求很高，”Exelixis执行副总裁，医学博士艾米·彼得森（AmyPeterson）说。

“Collectively, the results from the CONTACT-02 trial suggest that there are patients who could benefit from cabozantinib in combination with atezolizumab and that this regimen could be a valuable addition to the treatment landscape for patients with advanced prostate cancer.”.

“总的来说，CONTACT-02试验的结果表明，有些患者可以从卡博替尼联合atezolizumab中受益，这种方案可能是晚期前列腺癌患者治疗领域的一个有价值的补充。”。

Treatment-related grade 3-4 adverse events (AEs) occurred in 40% of patients receiving cabozantinib in combination with atezolizumab and 8% of those receiving NHT. Treatment-related AEs leading to discontinuation of all treatment components were similar (5% for cabozantinib in combination with atezolizumab and 2% of those receiving NHT).

接受cabozantinib联合atezolizumab治疗的患者中有40%发生治疗相关的3-4级不良事件（AE），接受NHT治疗的患者中有8%发生不良事件。导致停止所有治疗成分的治疗相关AE相似（cabozantinib联合atezolizumab组为5%，接受NHT组为2%）。

The time to clinically meaningful deterioration in quality of life was similar between arms, and the combination of cabozantinib and atezolizumab did not impair quality of life relative to generally well-tolerated NHT..

两组之间临床上有意义的生活质量恶化的时间相似，相对于一般耐受性良好的NHT，cabozantinib和atezolizumab的组合不会损害生活质量。。

As previously announced, CONTACT-02 met one of its two primary endpoints, demonstrating a statistically significant benefit in PFS in the predefined PFS ITT population (i.e., the first 400 randomized patients). Detailed results were presented at the American Society of Clinical Oncology 2024 Genitourinary Cancers Symposium in January 2024.

如前所述，CONTACT-02符合其两个主要终点之一，表明在预定义的PFS ITT人群（即前400名随机患者）中，PFS具有统计学上的显着益处。详细结果于2024年1月在美国临床肿瘤学会2024泌尿生殖系统癌症研讨会上发表。

Exelixis intends to submit a supplemental New Drug Application with the U.S. Food and Drug Administration for cabozantinib in combination with atezolizumab for mCRPC later this year..

Exelixis打算在今年晚些时候向美国食品和药物管理局提交一份补充新药申请，用于卡博替尼联合atezolizumab治疗mCRPC。。

About CONTACT-02

关于CONTACT-02

CONTACT-02 is a global, multicenter, randomized, phase 3, open-label study that randomized 575 patients 1:1 to the experimental arm of cabozantinib in combination with atezolizumab and the control arm of a second NHT (either abiraterone and prednisone or enzalutamide). The two primary endpoints of the trial are PFS and OS.

CONTACT-02是一项全球性，多中心，随机，3期，开放标签研究，将575名患者1:1随机分配到cabozantinib联合atezolizumab的实验组和第二次NHT（阿比特龙和泼尼松或enzalutamide）的对照组。该试验的两个主要终点是PFS和OS。

The study included patients with mCRPC who have measurable extra-pelvic soft tissue metastasis and who have progressed on one prior NHT. The secondary endpoint is objective response rate per blinded independent radiology committee. The trial is sponsored by Exelixis and co-funded by Ipsen, Roche and Takeda Pharmaceutical Company Limited (Takeda).

。次要终点是每个盲法独立放射学委员会的客观缓解率。该试验由Exelixis赞助，由Ipsen，Roche和武田制药有限公司（武田）共同资助。

Takeda is conducting the trial in Japan. More information about CONTACT-02 is available at ClinicalTrials.gov..

武田正在日本进行试验。有关CONTACT-02的更多信息，请访问ClinicalTrials.gov。。

About CRPC

关于CRPC

According to the American Cancer Society, approximately 299,000 new cases of prostate cancer will be diagnosed in the U.S., and over 35,000 people will die from the disease in 2024.1 Prostate cancer that has spread beyond the prostate and does not respond to androgen-suppression therapies—a common treatment for prostate cancer—is known as mCRPC.2 Men diagnosed with mCRPC often have a poor prognosis, with an estimated survival of 1-2 years.3,4.

据美国癌症协会（American Cancer Society）称，美国将诊断出约299000例前列腺癌新病例，2024年将有35000多人死于该疾病。1前列腺癌已扩散到前列腺以外，对雄激素抑制疗法无反应-前列腺癌的一种常见治疗方法称为mCRPC。2被诊断患有mCRPC的男性预后通常较差，估计生存期为1-2年[3,4]。

About CABOMETYX® (cabozantinib)

关于CABOMETYX® （卡博扎替尼）

In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

在美国，CABOMETYX片剂被批准作为治疗晚期肾细胞癌（RCC）患者的单一疗法，并与nivolumab联合作为晚期RCC患者的一线治疗；用于治疗先前接受索拉非尼治疗的肝细胞癌（HCC）患者；对于12岁及以上的患有局部晚期或转移性分化型甲状腺癌（DTC）的成人和儿科患者，这些患者在先前的VEGFR靶向治疗后已经进展，并且是放射性碘难治性或不合格的。

CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the European Union. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan.

CABOMETYX平板电脑还获得了美国和日本以外65多个国家（包括欧盟）的监管部门批准。2016年，Exelixis授予了Ipsen Pharma SAS在美国和日本以外的卡博替尼商业化和进一步临床开发的专有权。

In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S..

2017年，Exelixis授予武田制药有限公司独家权利，用于卡博替尼在日本所有未来适应症的商业化和进一步临床开发。Exelixis拥有在美国开发和商业化cabozantinib的独家权利。。

CABOMETYX is not indicated as a treatment for CRPC.

CABOMETYX不适用于CRPC的治疗。

IMPORTANT SAFETY INFORMATION

重要安全信息

WARNINGS AND PRECAUTIONS

警告和注意事项

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena..

出血：CABOMETYX发生严重致命的出血。在RCC，HCC和DTC研究中，CABOMETYX患者3至5级出血事件的发生率为5%。根据建议，在手术前停用CABOMETYX治疗3级或4级出血。不要给近期有出血史的患者服用CABOMETYX，包括咯血、呕血或黑便。。

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation..

。1%的CABOMETYX患者发生胃肠道（GI）穿孔，包括致命病例。监测患者瘘管和穿孔的体征和症状，包括脓肿和败血症。对于经历4级瘘管或胃肠道穿孔的患者，停止使用CABOMETYX。。

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention..

血栓事件：CABOMETYX增加了血栓事件的风险。静脉血栓栓塞发生率为7%（包括4%的肺栓塞），动脉血栓栓塞发生率为2%。CABOMETYX患者发生致命的血栓形成事件。对于发生急性心肌梗死或需要医疗干预的严重动脉或静脉血栓栓塞事件的患者，停用CABOMETYX。。

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment.

高血压和高血压危象：CABOMETYX可引起高血压，包括高血压危象。据报道，CABOMETYX患者中有37%（3级16%，4级1%）患有高血压。不要在未控制的高血压患者中启动CABOMETYX。在CABOMETYX治疗期间定期监测血压。

Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis..

保留CABOMETYX治疗未经医疗管理充分控制的高血压；控制后，以减少的剂量恢复。对于抗高血压治疗无法控制的严重高血压或高血压危象，永久停用CABOMETYX。。

Diarrhea: Diarrhea occurred in 62% of CABOMETYX patients. Grade 3 diarrhea occurred in 10% of CABOMETYX patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1, resume at a reduced dose.

腹泻：62%的CABOMETYX患者发生腹泻。10%的CABOMETYX患者发生3级腹泻。按照指示监测和管理使用止泻药的患者。停止CABOMETYX直至改善至≤1级，以减少的剂量恢复。

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 45% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

掌底红细胞感觉异常（PPE）：45%的CABOMETYX患者发生PPE。13%的CABOMETYX患者发生3级PPE。扣留CABOMETYX直至改善至1级，并以减少的剂量恢复不可忍受的2级PPE或3级PPE。

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

肝毒性：与单独使用CABOMETYX相比，CABOMETYX联合nivolumab可引起肝毒性，3级和4级ALT和AST升高的频率更高。

Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

在开始治疗之前和整个治疗过程中定期监测肝酶。考虑比药物作为单一药物给药时更频繁地监测肝酶。。

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

CABOMETYX和nivolumab联合使用后，11%的患者出现3级和4级ALT或AST升高。83例患者报告ALT或AST>3倍ULN（2级以上），其中23例（28%）接受全身皮质类固醇治疗；ALT或AST在74（89%）中降至0-1级。在44例ALT或AST≥2级升高的患者中，接受CABOMETYX（n=9）或nivolumab（n=11）作为单一药物或两者（n=24）再次攻击的患者中，2例接受CABOMETYX治疗的患者，2例接受nivolumab治疗的患者和7例接受CABOMETYX和nivolumab治疗的患者观察到ALT或AST≥2级升高的复发。

Withhold and resume at a reduced dose based on severity..

。。

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity..

肾上腺功能不全：CABOMETYX联合nivolumab可引起原发性或继发性肾上腺功能不全。对于2级或更高级别的肾上腺功能不全，开始对症治疗，包括临床指示的激素替代。停止CABOMETYX和/或nivolumab，并根据严重程度以减少的剂量恢复CABOMETYX。。

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC..

肾上腺皮质功能不全发生率为4.7%（15/320），接受CABOMETYX联合nivolumab治疗的RCC患者，包括3级（2.2%）和2级（1.9%）不良反应。肾上腺皮质功能不全导致0.9%的患者永久停用CABOMETYX和nivolumab，2.8%的RCC患者停用CABOMETYX和nivolumab。。

Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency..

大约80%（12/15）的肾上腺功能不全患者接受了激素替代疗法，包括全身皮质类固醇。15例患者中有27%（n=4）肾上腺功能不全得到缓解。在9例因肾上腺功能不全而停用CABOMETYX和nivolumab的患者中，有6例在症状改善后恢复治疗；其中，所有（n=6）接受激素替代治疗，2例肾上腺功能不全复发。。

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome..

蛋白尿：在8%的CABOMETYX患者中观察到蛋白尿。在CABOMETYX治疗期间定期监测尿蛋白。对于2级或3级蛋白尿，停止CABOMETYX直至改善至≤1级蛋白尿；以减少的剂量恢复CABOMETYX。肾病综合征患者停用CABOMETYX。。

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment.

颌骨坏死（ONJ）：ONJ发生率低于1%的CABOMETYX患者。ONJ可表现为颌骨疼痛，骨髓炎，骨炎，骨侵蚀，牙齿或牙周感染，牙痛，牙龈溃疡或侵蚀，持续性颌骨疼痛或牙科手术后口腔或颌骨愈合缓慢。在CABOMETYX开始之前和治疗期间定期进行口腔检查。

Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution, resume at a reduced dose..

建议患者注意良好的口腔卫生习惯。如果可能的话，在预定的牙科手术或侵入性牙科手术之前，扣留CABOMETYX至少3周。保留CABOMETYX用于ONJ的开发，直到完全解决为止，以减少的剂量恢复。。

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established..

。在择期手术前，保留CABOMETYX至少3周。大手术后至少2周内不要使用CABOMETYX，直到伤口充分愈合。伤口愈合并发症解决后恢复CABOMETYX的安全性尚未确定。。

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

可逆性后部白质脑病综合征（RPLS）：RPLS是一种通过MRI特征性发现诊断出的皮质下血管源性水肿综合征，可与CABOMETYX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。

Discontinue CABOMETYX in patients who develop RPLS..

在发生RPL的患者中停用CABOMETYX。。

Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Based on the safety population, thyroid dysfunction occurred in 19% of patients treated with CABOMETYX, including Grade 3 in 0.4% of patients.

。根据安全人群，使用CABOMETYX治疗的患者中有19%发生甲状腺功能障碍，其中0.4%的患者发生3级。

Patients should be assessed for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitored for signs and symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid function testing and management of dysfunction should be performed as clinically indicated.

在开始使用CABOMETYX之前，应评估患者的甲状腺功能障碍迹象，并在CABOMETYX治疗期间监测甲状腺功能障碍的体征和症状。甲状腺功能测试和功能障碍管理应按照临床指示进行。

Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on the safety population, hypocalcemia occurred in 13% of patients treated with CABOMETYX, including Grade 3 in 2% and Grade 4 in 1% of patients. Laboratory abnormality data were not collected in CABOSUN.

低钙血症：CABOMETYX可引起低钙血症。根据安全人群，接受CABOMETYX治疗的患者中有13%发生低钙血症，其中3级为2%，4级为1%。CABOSUN未收集实验室异常数据。

In COSMIC-311, hypocalcemia occurred in 36% of patients treated with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of patients.

在COSMIC-311中，36%接受CABOMETYX治疗的患者发生低钙血症，其中3级为6%，4级为3%。

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

监测血钙水平，并在治疗期间根据需要更换钙。根据严重程度，在恢复后以减少的剂量停止并恢复或永久停用CABOMETYX。

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose..

胚胎-胎儿毒性：CABOMETYX可引起胎儿伤害。建议孕妇和女性注意胎儿潜在风险的生殖潜力。在开始使用CABOMETYX之前，验证具有生殖潜力的女性的妊娠状况，并建议他们在治疗期间和最后一次给药后4个月内使用有效的避孕措施。。

ADVERSE REACTIONS

不良反应

The most common (≥20%) adverse reactions are:

最常见（≥20%）的不良反应是：

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

CABOMETYX作为单一药物：腹泻，疲劳，PPE，食欲下降，高血压，恶心，呕吐，体重下降和便秘。

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

CABOMETYX联合nivolumab：腹泻，疲劳，肝毒性，PPE，口腔炎，皮疹，高血压，甲状腺功能减退，肌肉骨骼疼痛，食欲下降，恶心，味觉障碍，腹痛，咳嗽和上呼吸道感染。

DRUG INTERACTIONS

药物相互作用

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

强CYP3A4抑制剂：如果无法避免与强CYP3A4抑制剂共同给药，请减少CABOMETYX剂量。避免葡萄柚或葡萄柚汁。

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

强CYP3A4诱导剂：如果无法避免与强CYP3A4诱导剂共同给药，请增加CABOMETYX剂量。避免服用圣约翰草。

USE IN SPECIFIC POPULATIONS

在特定人群中使用

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

哺乳期：建议女性在CABOMETYX治疗期间和最终剂量后4个月内不要母乳喂养。

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

肝功能损害：对于中度肝功能损害的患者，减少CABOMETYX的剂量。严重肝功能损害患者应避免使用CABOMETYX。

Please see accompanying full Prescribing Information

请参阅随附的完整处方信息

https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.

https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

鼓励您向FDA报告处方药的负面副作用。访问www.FDA.gov/medwatch或致电1-800-FDA-1088。

About Exelixis

Exelixis

Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics.

Exelixis是一家全球野心勃勃的肿瘤公司，在癌症护理的前沿创新下一代药物和方案。凭借卓越的药物发现和开发能力，我们正在迅速发展我们的产品组合，以通过我们临床上分化的小分子，抗体-药物偶联物和其他生物治疗药物的渠道，针对不断扩大的肿瘤类型和适应症。

This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future.

这种全面的方法利用了数十年来对我们的科学和合作伙伴关系的强劲投资，以推进我们的研究计划，并扩大我们的旗舰商业产品CABOMETYX®（cabozantinib）的影响。Exelixis是一项大胆的科学追求，旨在创造变革性治疗方法，为更多患者带来未来的希望。

For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn..

有关该公司及其帮助癌症患者恢复健康和长寿的使命的信息，请访问www.exelixis.com，在X（Twitter）上关注@ExelixisInc，就像在Facebook上关注exelixis，Inc.一样，在LinkedIn上关注exelixis。。

Forward-Looking Statements

前瞻性声明

This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of detailed final OS results from the CONTACT-02 trial at ESMO 2024; the therapeutic potential of cabozantinib in combination with atezolizumab to benefit patients with mCRPC and measurable extra-pelvic soft tissue disease who have progressed on one prior NHT, especially in the subset of patients with liver metastasis, and Exelixis’ belief that this combination regimen could be a valuable addition to the treatment landscape for patients with advanced prostate cancer; Exelixis’ plans to submit a supplemental New Drug Application with the U.S.

本新闻稿包含前瞻性声明，包括但不限于以下相关声明：介绍ESMO 2024年CONTACT-02试验的详细最终操作系统结果；cabozantinib联合atezolizumab对mCRPC和可测量的盆腔外软组织疾病患者的治疗潜力，这些患者在之前的一次NHT中取得了进展，特别是在肝转移患者亚组中，Exelixis认为这种联合治疗方案可能是对晚期前列腺癌患者治疗前景的有价值的补充；Exelixis计划向美国提交补充新药申请。

Food and Drug Administration for cabozantinib in combination with atezolizumab for mCRPC later this year; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections.

美国食品和药物管理局（FDA）在今年晚些时候将cabozantinib与atezolizumab联合用于mCRPC；以及Exelixis的科学追求，即创造变革性治疗方法，为更多患者带来未来的希望。任何涉及未来事件或情况的预期、预测或其他特征的陈述均为前瞻性陈述，并基于Exelixis当前的计划、假设、信念、期望、估计和预测。

Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the U.S.

前瞻性陈述涉及风险和不确定性。由于这些风险和不确定性，实际结果和事件发生的时间可能与前瞻性声明中预期的结果有重大差异，这些风险和不确定性包括但不限于：参考时间的数据可用性；美国监管审查和批准流程的复杂性和不可预测性。

and elsewhere; Exelixis’ continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials eval.

和其他地方；Exelixis继续遵守适用的法律和监管要求；由于不良安全事件的发生或临床试验评估的额外数据分析而可能出现的意外问题。

Exelixis, the Exelixis logo and CABOMETYX are registered U.S. trademarks of Exelixis.

Exelixis、Exelixis徽标和CABOMETYX是Exelixis的美国注册商标。

TECENTRIQ is registered U.S. trademark of Genentech, a member of the Roche Group.

TECENTRIQ是罗氏集团成员Genentech的美国注册商标。

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1癌症事实与数字2024。ACS公司。网址：https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf.2024年9月访问。

2 Patient education: Treatment for advanced prostate cancer (Beyond the Basics). UpToDate website. Available at: https://www.uptodate.com/contents/treatment-for-advanced-prostate-cancer-beyond-the-basics. Accessed September 2024.

2患者教育：治疗晚期前列腺癌（超越基础）。。网址：https://www.uptodate.com/contents/treatment-for-advanced-prostate-cancer-beyond-the-basics.2024年9月访问。

3 Freedland, S. J., et al. Real-world treatment patterns and overall survival among men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) in the US Medicare population. Prostate Cancer Prostatic Dis. 2023.

3 Freedland，S.J。等人。美国医疗保险人群中转移性去势抵抗性前列腺癌（mCRPC）男性的现实世界治疗模式和总体生存率。前列腺癌前列腺疾病。2023

4 Moreira, D. M., Howard, L. E., Sourbeer, K. N., et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017;15:60–66.e2

4 Moreira，D.M.，Howard，L.E.，Sourbeer，K.N。等人。预测去势抵抗性前列腺癌从转移到总生存的时间：搜索结果。。2017年；15： 60–66.e2