Exelixis Provides Regulatory Update Related to Supplemental New Drug Application for Cabozantinib (CABOMETYX) for the Treatment of Patients With Previously Treated Advanced Neuroendocrine Tumors
Exelixis Provides Regulatory Update Related to Supplemental New Drug Application for Cabozantinib (CABOMETYX) for the Treatment of Patients With Previously Treated Advanced Neuroendocrine Tumors
ALAMEDA, Calif.--(BUSINESS WIRE)--Nov. 26, 2024--Exelixis, Inc. (Nasdaq: EXEL) today announced that the U.S. Food and Drug Administration (FDA) has notified the company that the supplemental New Drug Application (sNDA) for cabozantinib (CABOMETYX) for the treatment of adults with previously treated advanced pancreatic neuroendocrine tumors (pNET) and advanced extra-pancreatic NET (epNET) will be discussed at an Oncologic Drugs Advisory Committee (ODAC) meeting in March 2025. The sNDA is based on the final results of the phase 3 CABINET pivotal trial, conducted by the National Cancer Institute's National Clinical Trials Network, evaluating cabozantinib compared with placebo in advanced pNET and advanced epNET. In August 2024, Exelixis announced that the FDA granted orphan drug designation to cabozantinib for the treatment of pNET and assigned a Prescription Drug User Fee Act target action date of April 3, 2025.
加利福尼亚州阿拉米达-（商业线）-2024年11月26日-伊克力西斯公司（纳斯达克：EXEL）今天宣布，美国食品药品监督管理局（FDA）已通知公司，用于治疗之前接受过治疗的晚期胰腺神经内分泌瘤（pNET）和晚期胰腺外NEt（epNET）成年人的卡波替尼（CABOMETYX）的补充新药申请（sNDA）将于2025年3月在肿瘤药物咨询委员会（ODAC）会议上讨论。sNDA基于由新华保险国家癌症研究所国家临床试验网络进行的CABINEt关键试验的最终结果，评估了卡波替尼与安慰剂在晚期pNEt和晚期epNEt中的作用。2024年8月，伊克力西斯宣布FDA授予卡波替尼治疗pNEt的孤儿药品贴士，并指定了2025年4月3日的处方药用户费行动日期。
As announced in August 2023, the Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board unanimously recommended that enrollment in the CABINET trial be stopped and randomized patients be unblinded to therapy with the allowance for crossover from placebo to cabozantinib due to the substantial improvement in progression-free survival (PFS) observed at this interim analysis. Final results from the enrolled patient population, which were presented at the 2024 European Society of Medical Oncology Congress and published concurrently in the New England Journal of Medicine, confirmed statistically significant and clinically meaningful improvements with cabozantinib versus placebo in the primary endpoint of PFS by blinded independent central review. Additional analyses supported consistency of benefit across all clinical subgroups examined, including primary tumor site, grade and prior systemic anticancer therapy.
根据2023年8月的公告，临床肿瘤研究联盟独立数据与安全监测委员会一致建议停止CABINEt试验的招募，并使随机分配的患者能够公开治疗，允许从安慰剂换至卡博替尼，因为在此中期分析中观察到进展无病生存（PFS）的实质性改善。来自入选患者群体的最终结果，在2024年欧洲医学肿瘤学会议上发布，并同时发表在《新英格兰医学杂志》上，确认了在主要终点PFS中，卡博替尼与安慰剂相比的统计学意义和临床意义上的改善。其他分析支持卡博替尼相对与安慰剂在主要肿瘤部位、等级和先前系统抗癌治疗中的一致受益。
ODACs review and evaluate data regarding the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cancer and make recommendations to the Commissioner of Food and Drugs. More general information about ODAC reviews can be found on the FDA website, here. The planned ODAC meeting is not related to the current approved indications for CABOMETYX in the U.S.
ODAC审查和评估有关治疗癌症使用的上市和研究人用药物的安全性和有效性的数据，并向食品药品监督管理局委员提交建议。有关ODAC审查的更一般信息可以在FDA网站上找到。计划中的ODAC会议与卡博替尼在美国获得批准的当前适应症无关。
About CABINET (Alliance A021602)
关于 CABINEt（联盟 A021602）
CABINET (Randomized, Double-Blinded Phase III Study of CABozantinib versus Placebo In Patients with Advanced NEuroendocrine Tumors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network as part of Exelixis' collaboration through a Cooperative Research and Development Agreement with the NCI's Cancer Therapy Evaluation Program.
CABINEt（随机、双盲的 CABozantinib 相对于对照组的 III 期研究，用于已经进行了先前治疗的患有晚期神经内分泌肿瘤的患者）由国家癌症研究所（NCI）赞助，是国家卫生研究院的一部分，并通过与 NCI 癌症治疗评估计划的合作研究与开发协议进行领导和管理。
CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase 3 pivotal trial that had enrolled a total of 298 patients in the U.S at the time of the final analysis. Patients were randomized 2:1 to cabozantinib (60 mg) or placebo in two separately powered cohorts (pNET, n=95; epNET, n=203). The epNET cohort included patients with the following primary tumor sites: gastrointestinal (GI) tract, lung, unknown primary sites and other. Each cohort was randomized separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by blinded independent central review. Secondary endpoints included overall survival, radiographic response rate and safety. More information about this trial is available at ClinicalTrials.gov.
CABINEt是一项多中心、随机、双盲、安慰剂对照的3期关键试验，在最终分析时在美国招募了298名患者。患者以2:1的比例随机分配到卡波替尼（60毫克）或安慰剂，分别组成两个独立的动力学队列（pNEt, n=95; epNEt, n=203）。epNEt队列包括以下原发肿瘤部位的患者：胃肠道，肺，原发部位未知的患者等。每个队列都被分别随机分配，并有自己的统计分析计划。患者必须满足RECISt 1.1标准的可测量疾病，并且在除体析生长抑素类似物之外的至少一条美国FDA批准的治疗线之后，出现病情进展或耐受性不佳。每个队列的主要终点是根据被盲目独立中心审查的RECISt 1.1标准进行的无进展生存期（PFS）。次要终点包括总生存期、放射影像学反应率和安全性。有关该试验的更多信息，请参阅ClinicalTrials.gov。
About Neuroendocrine Tumors (NET)
关于神经内分泌肿瘤（NET）
NET are cancers that begin in the specialized cells of the body's neuroendocrine system.1 These cells have traits of both hormone-producing endocrine cells and nerve cells.1 In the U.S., it is estimated that 161,000 to 192,000 people are living with unresectable, locally advanced or metastatic NET.2 The number of people diagnosed with NET has been increasing in recent decades.3 Functional NET release peptide hormones that can cause debilitating symptoms, like diarrhea, hypertension and flushing which may require focused treatment, while symptoms of non-functional NET are related primarily to tumor growth.4,5 Most NET take years to develop and grow slowly, but eventually all patients with advanced or metastatic NET will develop refractory and progressing disease.6,7
NET是起始于人体神经内分泌系统特殊细胞的癌症。1这些细胞具有激素产生内分泌细胞和神经细胞的特性。1在美国，估计有16.1万至19.2万人患有无法切除的、局部晚期或转移性NET。2近几十年来，NET的确诊人数不断增加。3功能性NET会释放引起症状严重并导致需要专注治疗的肽类激素，如腹泻、高血压和潮红，而非功能性NET的症状主要与肿瘤生长有关。4、5大多数NET需要数年的时间才能发展并缓慢生长，但最终所有晚期或转移性NET的患者都会发展为难治性和进展性疾病。6、7
NET can develop in any part of the body, but most commonly start in the GI tract or in the lungs, where they have historically been referred to as carcinoid tumors and are more recently called epNET.1 The five-year survival rates for advanced GI and lung NET tumors are 68% and 55%, respectively.8,9 NET can also start in the pancreas, where they tend to be more aggressive, with a five-year survival rate of only 23% for advanced disease. 1,10 For advanced NET patients, treatment options include somatostatin analogs, chemotherapy, targeted therapy and peptide-receptor radionuclide therapy.11
NET可以在身体的任何部位发展，但最常见的是在胃肠道或肺部开始，在这些部位，它们以往被称为类癌瘤，最近更被称为EPNET。晚期胃肠道和肺部NET肿瘤的五年生存率分别为68%和55%。NET也可以起源于胰腺，这种情况下更具侵袭性，晚期疾病的五年生存率仅为23%。对于晚期NET患者，治疗选择包括生长抑素类似物、化疗、靶向治疗和肽受体放射性核素治疗。
About CABOMETYX (cabozantinib)
关于 CABOMETYX（cabozantinib）
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 for patients 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. 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. 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.
在美国，CABOMETYX片剂被批准作为单药治疗晚期肾细胞癌（RCC）的患者以及与尼伐卢麦联合用于晚期肾细胞癌的一线治疗；用于曾接受索拉非尼治疗的肝细胞癌（HCC）患者的治疗；以及对于年龄12岁及以上的局部晚期或转移性分化型甲状腺癌（DTC），在经过靶向VEGFR治疗进展并且对放射性碘耐受或不合适的患者。CABOMETYX片剂还已在包括美国和日本在内的全球65多个国家获得了监管批准，包括欧盟。2016年，Exelixis授予伊普生制药SAS公司在美国和日本以外地区独家权利进行卡博替尼的商业化和进一步临床开发。2017年，Exelixis授予武田制药有限公司在日本所有未来适应症的卡博替尼的商业化和进一步临床开发的独家权利。Exelixis在美国拥有卡博替尼的独家开发和商业化权利。
CABOMETYX is not indicated as a treatment for NET.
CABOMETYX不能作为NET的治疗方法。
IMPORTANT SAFETY INFORMATION
重要安全信息
WARNINGS AND PRECAUTIONS
警示和注意事项
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：使用CABOMETYX时出现严重和致命的出血事件。在治疗晚期肾癌、肝癌和甲状腺癌的CABOMETYX患者中，出血事件的3至5级发生率为5%。建议在手术前和出现3或4级出血时停止CABOMETYX的使用。不要给最近有过出血事件，包括咳血、呕血或黑便的患者用CABOMETYX。
Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. 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.
穿孔和瘘管：哌替尼（CABOMETYX）患者中发生瘘管，包括致命病例，在1%的患者中发生。GI穿孔，包括致命病例，在1%的CABOMETYX患者中发生。监测患者是否出现瘘管和穿孔的迹象和症状，包括脓肿和败血症。对于出现4级瘘管或GI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会增加血栓事件的风险。 CABOMETYX患者中7%出现静脉血栓栓塞（包括4%肺栓塞）和2%的动脉栓塞。CABOMETYX患者中也会发生致命的血栓事件。在出现急性心肌梗塞或需要医学干预的严重动脉或静脉血栓栓塞事件的患者中停止CABOMETYX的使用。
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. 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.
CABOMETYX可能引起高血压和高血压危机，CABOMETYX患者中有37%（16%为3级，＜1%为4级）出现高血压。不要将CABOMETYX用于未控制的高血压患者。在CABOMETYX治疗期间定期监测血压。对于无法通过药物治疗充分控制的高血压，暂停CABOMETYX；当其受控时，以减量形式恢复。无法通过抗高血压疗法或高血压危机充分控制的严重高血压永久性停用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：CABOMETYX 患者中腹泻发生率为 62%。CABOMETYX 患者中 3 级腹泻的发生率为 10%。根据需要使用抗腹泻药监测和管理患者，直至达到≤ 1 级的改善，再以降低的剂量恢复使用。
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.
手掌-足底红斑病（PPE）发生率为CABOMETYX患者的45%。CABOMETYX患者中有13%出现PPE 3级者。对于无法耐受的2级PPE或3级PPE，停用CABOMETYX直到改善为1级并以减量恢复。
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.
CABOMETYX与nivolumab联合使用可能会导致肝毒性，肝酶升高的3、4级不良反应的频率较CABOMETYX单独使用更高。
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.
在治疗开始前及其周期性进行肝酶检查。比药物单独使用时，应更频繁地监测肝酶。对于肝酶升高，中断CABOMETYX和nivolumab，考虑给予皮质类固醇。
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. Withhold and resume at a reduced dose based on severity.
使用 CABOMETYX 和 nivolumab 联合治疗，11% 的患者出现了 3 级到 4 级的肝转氨酶升高。83 名患者报道了肝转氨酶水平 >3 倍上限（≥2 级），其中 23 名（28%）接受了系统性皮质类固醇治疗；肝转氨酶水平在 74 名患者中恢复为 0-1 级，占 89%。重新挑战 CABOMETYX（n = 9）或 nivolumab（n = 11）或两者合用（n = 24）的 44 名合格患者中，CABOMETYX 治疗的 2 名患者，nivolumab 治疗的 2 名患者和两者共同使用的 7 名患者出现了再次出现 ≥2 级肝酶升高的情况。根据严重程度暂停治疗并恢复到降低的剂量。
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.
CABOMETYX与nivolumab联合使用可能引起原发性或继发性肾上腺功能减退。对于2级或更高的肾上腺功能减退，根据临床表现，采取症状性治疗，包括激素替代治疗。根据严重程度，暂停CABOMETYX和/或nivolumab，并恢复CABOMETYX以减量形式。
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.
在接受CABOMETYX和nivolumab治疗的RCC患者中，4.7％（15/320）出现肾上腺功能减退，包括3级（2.2％）和2级（1.9％）不良反应。肾上腺功能减退导致0.9％的患者永久性停用CABOMETYX和nivolumab，以及2.8％的患者暂停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％的肾上腺功能减退患者（12/15）接受了激素替代治疗，包括全身皮质类固醇。15名患者中27％（n=4）肾上腺功能减退已得到缓解；在那些CABOMETYX和nivolumab被暂停的9名患者中，6名症状得到改善后重新开始治疗；其中，这6名患者都接受了激素替代治疗，而2名患者肾上腺功能减退出现再次发作。
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：CABOMETYX 患者中观察到蛋白尿发生率为 8%。在 CABOMETYX 治疗期间定期监测尿蛋白质。对于 2 级或 3 级蛋白尿，暂停使用 CABOMETYX，直至改善到 ≤1 级蛋白尿，以降低的剂量恢复使用。对于出现肾病综合征的患者，停止使用 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. 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.
CABOMETYX患者中出现颌骨坏死的比例＜1％。颌骨坏死可能表现为颌部疼痛、骨髓炎、骨炎、骨蚀、牙或牙周感染、牙痛、牙龈溃疡或侵蚀、持续性颌痛或牙科手术后口腔或颌部愈合缓慢。进行CABOMETYX治疗前和治疗期间及时进行口腔检查；建议患者遵循良好的口腔卫生习惯。在可能的情况下，预定口腔手术或侵入性口腔程序前至少暂停CABOMETYX 3周。对于颌骨坏死的出现，暂停CABOMETYX直至完全恢复，以减量恢复。
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.
CABOMETYX中出现手术伤口并发症。在择期手术之前，停用CABOMETYX至少3周。在重大手术之后至少2周不要用CABOMETYX，并等到切口完全愈合才使用CABOMETYX。尚未确立手术伤口完全愈合后再次使用CABOMETYX的安全性。
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. Discontinue CABOMETYX in patients who develop RPLS.
RPLS是一种亚皮质脑白质的水肿性综合征，诊断基于MRI上的特征发现，CABOMETYX可以引起RPLS。对于出现癫痫、头痛、视觉障碍、混乱或意识改变的患者进行RPLS评估。发现RPLS时停用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.
甲状腺功能异常，主要是甲状腺减低，已通过CABOMETYX观察到。根据安全人群统计，20％的CABOMETYX患者出现了甲状腺功能异常，包括0.4％的3级患者。在开始CABOMETYX之前，应评估患者是否有甲状腺功能异常，并在CABOMETYX治疗期间监测甲状腺功能异常的表现和症状。应根据临床指标进行甲状腺功能检测和治疗。
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CABOMETYX之前，应评估患者是否有甲状腺异常，并在CABOMETYX治疗期间监测甲状腺异常的表现和症状。应根据临床指标进行甲状腺功能检测和治疗。
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.
CABOMETYX可以引起低钙血症。在安全人群中，13％的CABOMETYX患者出现低钙血症，其中2％是3级，1％是4级的。未在CABOSUN中收集实验室异常数据。在COSMIC-311中，有36％的接受CABOMETYX治疗的患者出现低钙血症，其中有6％的患者是3级的，3％的患者为4级的。在治疗期间监测血钙水平，并根据需要进行钙补充治疗。根据严重程度暂停治疗，并以减量方式恢复，或永久性停用CABOMETYX。
In COSMIC-311, hypocalcemia occurred in 36% of patients treated with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of patients.
在治疗过程中，CABOMETYX患者中＜1％出现低钙血症。
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.
在治疗期间监测血钙水平，并根据需要进行钙补充治疗。根据严重程度暂停治疗，并以减量方式恢复，或永久性停用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.
CABOMETYX可能会导致胚胎/胎儿毒性。通知孕妇和有生育能力的女性胎儿存在潜在危险。在开始CABOMETYX之前，确认有生育能力女性的怀孕情况，并建议她们在治疗期间使用有效的避孕措施，在最后一剂药后持续4个月。
ADVERSE REACTIONS
不良反应
The most common (≥20%) adverse reactions are:
最常见（≥20%）的不良反应为：
CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.
CABOMETYX作为单一作用剂：腹泻、疲劳、PPE、食欲减退、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与nivolumab联合使用：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、食欲减退、恶心、味觉异常、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抑制剂联合使用，请减少CABOMETYX剂量。避免食用西柚或西柚汁。
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诱导剂联合使用，请增加CABOMETYX剂量。避免使用圣约翰草。
USE IN SPECIFIC POPULATIONS
特定人群的使用
Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.
哺乳期：劝告妇女在CABOMETYX治疗期间和治疗结束后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患者，应减少CABOMETYX剂量。在重度肝功能损害患者中应避免使用CABOMETYX。
Please see accompanying full Prescribing Information
.
请参阅随附的完整处方信息
.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088.
FDA鼓励您向其报告处方药物的负面副作用。请访问网站 或拨打1-800-FDA-1088。
About Exelixis
伊克力西斯是一家全球有雄心的肿瘤学公司，在肿瘤治疗前沿创新下一代药物和方案。凭借药物发现和开发的卓越性，我们正在迅速发展产品组合，利用小分子、抗体-药物联合物和其他生物制品的临床差异化管道，以瞄准不断扩大的肿瘤类型和指征范围。这种全面的方法利用数十年的科学和合作伙伴投资，在推进我们的调查计划和扩大我们的旗舰商业产品Cabometyx （cabozantinib）的影响。伊克力西斯受到大胆的科学追求的驱动，创建革命性的治疗方法，为更多患者带来未来的希望。有关该公司及其使癌症患者更强壮，生存更长久的使命的信息，请访问
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. 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. For information about the company and its mission to help cancer patients recover stronger and live longer, visit , follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn.
伊克力西斯是一家全球性肿瘤专业制药公司，致力于创新下一代医药和方案，处于癌症治疗的前沿。凭借药物发现和研发的卓越能力，公司正在快速拓展其产品系列，以针对不断扩大的肿瘤类型和适应症，通过小分子、抗体药物联用物和其他生物制药不断创新。这种综合性方法利用我们多年来在科技和合作伙伴关系上的丰厚投资，推动我们的研发项目不断前进，扩大我们旗舰商业产品CABOMETYX（卡波他尼）的影响。公司秉承一个大胆的科学追求，致力于创造变革性治疗方法，为更多的患者带来希望。有关公司及其帮助癌症患者更强有力地恢复并延长生命的使命，请访问 ，关注推特上的@ExelixisInc，点赞 Exelixis, Inc.的 Facebook 页面，并关注领英的 Exelixis。
Exelixis Forward-Looking Statements
伊克力西斯前瞻性声明
This press release contains forward-looking statements, including, without limitation, statements related to: the FDA's plans to discuss the sNDA for cabozantinib for the treatment of adults with previously treated advanced pNET and advanced epNET at an ODAC meeting in March 2025; the therapeutic potential of cabozantinib as a treatment for patients with previously treated advanced pNET and advanced epNET; the regulatory review process with respect to Exelixis' sNDA for cabozantinib in previously treated advanced pNET and advanced epNET, including the Prescription Drug User Fee Act target action date assigned by the FDA; and Exelixis' scientific pursuit to create transformational treatments that give patients more 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. 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: complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere, including the risk that the FDA may not approve cabozantinib as a treatment for pNET or epNET in a timely fashion, if at all; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors affecting the ability of Exelixis to obtain regulatory approval for cabozantinib in new indications detailed from time to time under the caption "Risk Factors" in Exelixis' most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis' future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.
本新闻稿包含前瞻性声明，包括但不限于以下内容：FDA计划在2025年3月的ODAC会议上讨论卡波替尼用于治疗先前接受过治疗的晚期pNEt和晚期epNEt的sNDA；卡波替尼作为治疗先前接受过治疗的晚期pNEt和晚期epNEt患者的治疗潜力；关于Exelixis提交的卡波替尼用于治疗先前接受过治疗的晚期pNEt和晚期epNEt的sNDA的监管审查过程，包括FDA指定的处方药用户费法案目标行动日期；以及Exelixis追求创造具有转化性治疗潜力的科学努力，为患者提供更多未来希望。任何涉及对未来事件或情况的期望、预测或其他描述的声明都是前瞻性声明，基于Exelixis当前的计划、假设、信念、期望、估计和投射。前瞻性声明涉及风险和不确定性。由于这些风险和不确定性，实际结果和事件的时间可能与前瞻性声明中预期的结果有实质不同。这些风险和不确定性包括但不限于：美国和其他地方监管审查和批准过程的复杂性和不可预测性，包括FDA可能不会及时批准卡波替尼用于治疗pNEt或epNEt，甚至可能不批准的风险；可能由于出现不良安全事件或对评估卡波替尼的临床试验的额外数据分析而出现的意外问题；Exelixis保护其知识产权的能力；市场竞争，包括竞争对手可能获得通用版本CABOMETYX的批准的潜力；经济和商业条件的变化；以及影响Exelixis获得卡波替尼在新适应症中监管批准能力的其他因素，这些因素从时间到时间在Exelixis的最新年度10-k表格的“风险因素”标题下以及以后的季度10-Q表格中详细阐述，并在Exelixis将来向证券交易委员会提交的文件中。本新闻稿中的所有前瞻性声明基于Exelixis截至本新闻稿日期的信息，Exelixis无义务更新或修订本处包含的任何前瞻性声明，除非法律要求。
Exelixis, the Exelixis logo and CABOMETYX are registered U.S. trademarks of Exelixis.
伊克力西斯、伊克力西斯公司商标和CABOMETYX为伊克力西斯的注册美国商标。
______________________________
1 Neuroendocrine Tumors. Cleveland Clinic website. Available at: . Accessed November 2024.
2 Population Estimate: Unresectable, Locally Advanced or Metastatic Extra-Pancreatic NET. June 2024 (internal data on file).
3 Pathak, S., Starr, J.S., Halfdanarson T., et al. Understanding the increasing incidence of neuroendocrine tumors. Expert Rev Endocrinol Metab. September 2023;18(5):377-385.
4 Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ)–Patient Version. NCI website. Available at: . Accessed November 2024.
5 What Is a Pancreatic Neuroendocrine Tumor? ACS website. Available at: . Accessed November 2024.
6 McClellan, K., Chen. E.Y, Kardosh A., et al. Therapy Resistant Gastroenteropancreatic Neuroendocrine Tumors. Cancers. 2022, 14(19), 4769.
7 What is a Gastrointestinal Carcinoid Tumor? ACS website. Available at: . Accessed November 2024.
8 Survival Rates for Gastrointestinal Carcinoid Tumors. ACS website. Available at: . Accessed November 2024.
9 Survival Rates for Lung Carcinoid Tumors. ACS website. Available at: . Accessed November 2024.
10 Survival Rates for Pancreatic Neuroendocrine Tumor. ACS website. Available at: . Accessed November 2024.
11 Neuroendocrine Tumor (NET). NCI website. Available at: . Accessed November 2024.
______________________________
1.神经内分泌肿瘤。克利夫兰诊所网站。网址：。2024年11月查看。
2 人口估计：不可切除、局部进展或转移性非胰腺外 NEt。 2024 年 6 月（内部文件）。
3 Pathak，S.，Starr，J.S.，Halfdanarson t.等。了解神经内分泌肿瘤不断增加的原因。专业评论内分泌代谢。2023年9月；18(5)：377-385。
4.胰腺神经内分泌肿瘤（岛细胞肿瘤）治疗（PDQ）- 患者版本。NCI网站。网址：。2024年11月查看。
5.什么是胰腺神经内分泌肿瘤？ ACS网站。网址：。2024年11月查看。
6 McClellan万。，Chen。E.Y，Kardosh A.等。治疗耐药的胃肠胰神经内分泌肿瘤。癌症。2022年，14(19)，4769。
7 什么是胃肠类癌症肿瘤? 美国癌症协会网站。网址：。2024 年 11 月访问。
8 胃肠类癌症肿瘤的存活率。美国癌症协会网站。网址：。2024 年 11 月访问。
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View source version on businesswire.com:
在businesswire.com上查看源版本：
Investors Contact:
Susan Hubbard
EVP, Public Affairs and
Investor Relations
Exelixis, Inc.
(650) 837-8194
shubbard@exelixis.com
投资者联系方式：
苏珊·哈伯德
公共事务和EVP
投资者关系
伊克力西斯股份有限公司
(650) 837-8194
shubbard@伊克力西斯.com
Media Contact:
Lindsay Treadway
VP, Public Affairs and Advocacy Relations
Exelixis, Inc.
(650) 837-7522
ltreadway@exelixis.com
媒体联系：
lindsay Treadway
副总裁，公共事务和倡导关系
伊克力西斯股份有限公司
(650) 837-7522
ltreadway@exelixis.com
Source: Exelixis, Inc.
来源：伊克力西斯股份有限公司。
