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.
加利福尼亞州阿拉米達-（商業線）-2024年11月26日-伊克力西斯公司（納斯達克：EXEL）今天宣佈，美國食品藥品監督管理局（FDA）已通知公司，用於治療之前接受過治療的晚期胰腺神經內分泌瘤（pNET）和晚期胰腺外NEt（epNET）成年人的卡波替尼（CABOMETYX）的補充新藥申請（sNDA）將於2025年3月在腫瘤藥物諮詢委員會（ODAC）會議上討論。sNDA基於由新華保險國家癌症研究所國家臨床試驗網絡進行的CABINEt關鍵試驗的最終結果，評估了卡波替尼與安慰劑在晚期pNEt和晚期epNEt中的作用。2024年8月，伊克力西斯宣佈FDA授予卡波替尼治療pNEt的孤兒藥品貼士，並指定了2025年4月3日的處方藥用戶費行動日期。
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.
根據2023年8月的公告，臨床腫瘤研究聯盟獨立數據與安全監測委員會一致建議停止CABINEt試驗的招募，並使隨機分配的患者能夠公開治療，允許從安慰劑換至卡博替尼，因爲在此中期分析中觀察到進展無病生存（PFS）的實質性改善。來自入選患者群體的最終結果，在2024年歐洲醫學腫瘤學會議上發佈，並同時發表在《新英格蘭醫學雜誌》上，確認了在主要終點PFS中，卡博替尼與安慰劑相比的統計學意義和臨床意義上的改善。其他分析支持卡博替尼相對與安慰劑在主要腫瘤部位、等級和先前系統抗癌治療中的一致受益。
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審查和評估有關治療癌症使用的上市和研究人用藥物的安全性和有效性的數據，並向食品藥品監督管理局委員提交建議。有關ODAC審查的更一般信息可以在FDA網站上找到。計劃中的ODAC會議與卡博替尼在美國獲得批准的當前適應症無關。
About CABINET (Alliance A021602)
關於 CABINEt（聯盟 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（隨機、雙盲的 CABozantinib 相對於對照組的 III 期研究，用於已經進行了先前治療的患有晚期神經內分泌腫瘤的患者）由國家癌症研究所（NCI）贊助，是國家衛生研究院的一部分，並通過與 NCI 癌症治療評估計劃的合作研究與開發協議進行領導和管理。
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是一項多中心、隨機、雙盲、安慰劑對照的3期關鍵試驗，在最終分析時在美國招募了298名患者。患者以2:1的比例隨機分配到卡波替尼（60毫克）或安慰劑，分別組成兩個獨立的動力學隊列（pNEt, n=95; epNEt, n=203）。epNEt隊列包括以下原發腫瘤部位的患者：胃腸道，肺，原發部位未知的患者等。每個隊列都被分別隨機分配，並有自己的統計分析計劃。患者必須滿足RECISt 1.1標準的可測量疾病，並且在除體析生長抑素類似物之外的至少一條美國FDA批准的治療線之後，出現病情進展或耐受性不佳。每個隊列的主要終點是根據被盲目獨立中心審查的RECISt 1.1標準進行的無進展生存期（PFS）。次要終點包括總生存期、放射影像學反應率和安全性。有關該試驗的更多信息，請參閱ClinicalTrials.gov。
About Neuroendocrine Tumors (NET)
關於神經內分泌腫瘤（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是起始於人體神經內分泌系統特殊細胞的癌症。1這些細胞具有激素產生內分泌細胞和神經細胞的特性。1在美國，估計有16.1萬至19.2萬人患有無法切除的、局部晚期或轉移性NET。2近幾十年來，NET的確診人數不斷增加。3功能性NET會釋放引起症狀嚴重並導致需要專注治療的肽類激素，如腹瀉、高血壓和潮紅，而非功能性NET的症狀主要與腫瘤生長有關。4、5大多數NET需要數年的時間才能發展並緩慢生長，但最終所有晚期或轉移性NET的患者都會發展爲難治性和進展性疾病。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可以在身體的任何部位發展，但最常見的是在胃腸道或肺部開始，在這些部位，它們以往被稱爲類癌瘤，最近更被稱爲EPNET。晚期胃腸道和肺部NET腫瘤的五年生存率分別爲68%和55%。NET也可以起源於胰腺，這種情況下更具侵襲性，晚期疾病的五年生存率僅爲23%。對於晚期NET患者，治療選擇包括生長抑素類似物、化療、靶向治療和肽受體放射性核素治療。
About CABOMETYX (cabozantinib)
關於 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.
在美國，CABOMETYX片劑被批准作爲單藥治療晚期腎細胞癌（RCC）的患者以及與尼伐盧麥聯合用於晚期腎細胞癌的一線治療；用於曾接受索拉非尼治療的肝細胞癌（HCC）患者的治療；以及對於年齡12歲及以上的局部晚期或轉移性分化型甲狀腺癌（DTC），在經過靶向VEGFR治療進展並且對放射性碘耐受或不合適的患者。CABOMETYX片劑還已在包括美國和日本在內的全球65多個國家獲得了監管批准，包括歐盟。2016年，Exelixis授予伊普生製藥SAS公司在美國和日本以外地區獨家權利進行卡博替尼的商業化和進一步臨床開發。2017年，Exelixis授予武田製藥有限公司在日本所有未來適應症的卡博替尼的商業化和進一步臨床開發的獨家權利。Exelixis在美國擁有卡博替尼的獨家開發和商業化權利。
CABOMETYX is not indicated as a treatment for NET.
CABOMETYX不能作爲NET的治療方法。
IMPORTANT SAFETY INFORMATION
重要安全信息
WARNINGS AND PRECAUTIONS
警示和注意事項
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時出現嚴重和致命的出血事件。在治療晚期腎癌、肝癌和甲狀腺癌的CABOMETYX患者中，出血事件的3至5級發生率爲5%。建議在手術前和出現3或4級出血時停止CABOMETYX的使用。不要給最近有過出血事件，包括咳血、嘔血或黑便的患者用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.
穿孔和瘻管：哌替尼（CABOMETYX）患者中發生瘻管，包括致命病例，在1%的患者中發生。GI穿孔，包括致命病例，在1%的CABOMETYX患者中發生。監測患者是否出現瘻管和穿孔的跡象和症狀，包括膿腫和敗血症。對於出現4級瘻管或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會增加血栓事件的風險。 CABOMETYX患者中7%出現靜脈血栓栓塞（包括4%肺栓塞）和2%的動脈栓塞。CABOMETYX患者中也會發生致命的血栓事件。在出現急性心肌梗塞或需要醫學干預的嚴重動脈或靜脈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可能引起高血壓和高血壓危機，CABOMETYX患者中有37%（16%爲3級，＜1%爲4級）出現高血壓。不要將CABOMETYX用於未控制的高血壓患者。在CABOMETYX治療期間定期監測血壓。對於無法通過藥物治療充分控制的高血壓，暫停CABOMETYX；當其受控時，以減量形式恢復。無法通過抗高血壓療法或高血壓危機充分控制的嚴重高血壓永久性停用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.
腹瀉：CABOMETYX 患者中腹瀉發生率爲 62%。CABOMETYX 患者中 3 級腹瀉的發生率爲 10%。根據需要使用抗腹瀉藥監測和管理患者，直至達到≤ 1 級的改善，再以降低的劑量恢復使用。
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-足底紅斑病（PPE）發生率爲CABOMETYX患者的45%。CABOMETYX患者中有13%出現PPE 3級者。對於無法耐受的2級PPE或3級PPE，停用CABOMETYX直到改善爲1級並以減量恢復。
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與nivolumab聯合使用可能會導致肝毒性，肝酶升高的3、4級不良反應的頻率較CABOMETYX單獨使用更高。
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.
在治療開始前及其週期性進行肝酶檢查。比藥物單獨使用時，應更頻繁地監測肝酶。對於肝酶升高，中斷CABOMETYX和nivolumab，考慮給予皮質類固醇。
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 聯合治療，11% 的患者出現了 3 級到 4 級的肝轉氨酶升高。83 名患者報道了肝轉氨酶水平 >3 倍上限（≥2 級），其中 23 名（28%）接受了系統性皮質類固醇治療；肝轉氨酶水平在 74 名患者中恢復爲 0-1 級，佔 89%。重新挑戰 CABOMETYX（n = 9）或 nivolumab（n = 11）或兩者合用（n = 24）的 44 名合格患者中，CABOMETYX 治療的 2 名患者，nivolumab 治療的 2 名患者和兩者共同使用的 7 名患者出現了再次出現 ≥2 級肝酶升高的情況。根據嚴重程度暫停治療並恢復到降低的劑量。
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與nivolumab聯合使用可能引起原發性或繼發性腎上腺功能減退。對於2級或更高的腎上腺功能減退，根據臨床表現，採取症狀性治療，包括激素替代治療。根據嚴重程度，暫停CABOMETYX和/或nivolumab，並恢復CABOMETYX以減量形式。
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治療的RCC患者中，4.7％（15/320）出現腎上腺功能減退，包括3級（2.2％）和2級（1.9％）不良反應。腎上腺功能減退導致0.9％的患者永久性停用CABOMETYX和nivolumab，以及2.8％的患者暫停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.
大約80％的腎上腺功能減退患者（12/15）接受了激素替代治療，包括全身皮質類固醇。15名患者中27％（n=4）腎上腺功能減退已得到緩解；在那些CABOMETYX和nivolumab被暫停的9名患者中，6名症狀得到改善後重新開始治療；其中，這6名患者都接受了激素替代治療，而2名患者腎上腺功能減退出現再次發作。
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 患者中觀察到蛋白尿發生率爲 8%。在 CABOMETYX 治療期間定期監測尿蛋白質。對於 2 級或 3 級蛋白尿，暫停使用 CABOMETYX，直至改善到 ≤1 級蛋白尿，以降低的劑量恢復使用。對於出現腎病綜合徵的患者，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患者中出現頜骨壞死的比例＜1％。頜骨壞死可能表現爲頜部疼痛、骨髓炎、骨炎、骨蝕、牙或牙周感染、牙痛、牙齦潰瘍或侵蝕、持續性頜痛或牙科手術後口腔或頜部癒合緩慢。進行CABOMETYX治療前和治療期間及時進行口腔檢查；建議患者遵循良好的口腔衛生習慣。在可能的情況下，預定口腔手術或侵入性口腔程序前至少暫停CABOMETYX 3周。對於頜骨壞死的出現，暫停CABOMETYX直至完全恢復，以減量恢復。
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中出現手術傷口併發症。在擇期手術之前，停用CABOMETYX至少3周。在重大手術之後至少2周不要用CABOMETYX，並等到切口完全癒合才使用CABOMETYX。尚未確立手術傷口完全癒合後再次使用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是一種亞皮質腦白質的水腫性綜合徵，診斷基於MRI上的特徵發現，CABOMETYX可以引起RPLS。對於出現癲癇、頭痛、視覺障礙、混亂或意識改變的患者進行RPLS評估。發現RPLS時停用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.
甲狀腺功能異常，主要是甲狀腺減低，已通過CABOMETYX觀察到。根據安全人群統計，20％的CABOMETYX患者出現了甲狀腺功能異常，包括0.4％的3級患者。在開始CABOMETYX之前，應評估患者是否有甲狀腺功能異常，並在CABOMETYX治療期間監測甲狀腺功能異常的表現和症狀。應根據臨床指標進行甲狀腺功能檢測和治療。
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.
在開始CABOMETYX之前，應評估患者是否有甲狀腺異常，並在CABOMETYX治療期間監測甲狀腺異常的表現和症狀。應根據臨床指標進行甲狀腺功能檢測和治療。
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可以引起低鈣血癥。在安全人群中，13％的CABOMETYX患者出現低鈣血癥，其中2％是3級，1％是4級的。未在CABOSUN中收集實驗室異常數據。在COSMIC-311中，有36％的接受CABOMETYX治療的患者出現低鈣血癥，其中有6％的患者是3級的，3％的患者爲4級的。在治療期間監測血鈣水平，並根據需要進行鈣補充治療。根據嚴重程度暫停治療，並以減量方式恢復，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.
在治療過程中，CABOMETYX患者中＜1％出現低鈣血癥。
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.
在治療期間監測血鈣水平，並根據需要進行鈣補充治療。根據嚴重程度暫停治療，並以減量方式恢復，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可能會導致胚胎/胎兒毒性。通知孕婦和有生育能力的女性胎兒存在潛在危險。在開始CABOMETYX之前，確認有生育能力女性的懷孕情況，並建議她們在治療期間使用有效的避孕措施，在最後一劑藥後持續4個月。
ADVERSE REACTIONS
不良反應
The most common (≥20%) adverse reactions are:
最常見（≥20%）的不良反應爲：
CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.
CABOMETYX作爲單一作用劑：腹瀉、疲勞、PPE、食慾減退、高血壓、噁心、嘔吐、體重下降和便秘。
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與nivolumab聯合使用：腹瀉、疲勞、肝毒性、PPE、口腔炎、皮疹、高血壓、甲狀腺功能減退、肌肉骨骼疼痛、食慾減退、噁心、味覺異常、腹痛、咳嗽和上呼吸道感染。
DRUG INTERACTIONS
藥物相互作用
Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.
強CYP3A4抑制劑：如果無法避免與強CYP3A4抑制劑聯合使用，請減少CABOMETYX劑量。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.
強CYP3A4誘導劑：如果無法避免與強CYP3A4誘導劑聯合使用，請增加CABOMETYX劑量。避免使用聖約翰草。
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：勸告婦女在CABOMETYX治療期間和治療結束後4個月內不要母乳餵養。
Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.
肝功能損害：對於中度肝功能損害患者，應減少CABOMETYX劑量。在重度肝功能損害患者中應避免使用CABOMETYX。
Please see accompanying full Prescribing Information
.
請參閱隨附的完整處方信息
.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088.
FDA鼓勵您向其報告處方藥物的負面副作用。請訪問網站 或撥打1-800-FDA-1088。
About Exelixis
伊克力西斯是一家全球有雄心的腫瘤學公司，在腫瘤治療前沿創新下一代藥物和方案。憑藉藥物發現和開發的卓越性，我們正在迅速發展產品組合，利用小分子、抗體-藥物聯合物和其他生物製品的臨床差異化管道，以瞄準不斷擴大的腫瘤類型和指徵範圍。這種全面的方法利用數十年的科學和合作夥伴投資，在推進我們的調查計劃和擴大我們的旗艦商業產品Cabometyx （cabozantinib）的影響。伊克力西斯受到大膽的科學追求的驅動，創建革命性的治療方法，爲更多患者帶來未來的希望。有關該公司及其使癌症患者更強壯，生存更長久的使命的信息，請訪問
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腫瘤專業製藥公司，致力於創新下一代醫藥和方案，處於癌症治療的前沿。憑藉藥物發現和研發的卓越能力，公司正在快速拓展其產品系列，以針對不斷擴大的腫瘤類型和適應症，通過小分子、抗體藥物聯用物和其他生物製藥不斷創新。這種綜合性方法利用我們多年來在科技和合作夥伴關係上的豐厚投資，推動我們的研發項目不斷前進，擴大我們旗艦商業產品CABOMETYX（卡波他尼）的影響。公司秉承一個大膽的科學追求，致力於創造變革性治療方法，爲更多的患者帶來希望。有關公司及其幫助癌症患者更強有力地恢復並延長生命的使命，請訪問 ，關注推特上的@ExelixisInc，點贊 Exelixis, Inc.的 Facebook 頁面，並關注領英的 Exelixis。
Exelixis Forward-Looking Statements
伊克力西斯前瞻性聲明
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.
本新聞稿包含前瞻性聲明，包括但不限於以下內容：FDA計劃在2025年3月的ODAC會議上討論卡波替尼用於治療先前接受過治療的晚期pNEt和晚期epNEt的sNDA；卡波替尼作爲治療先前接受過治療的晚期pNEt和晚期epNEt患者的治療潛力；關於Exelixis提交的卡波替尼用於治療先前接受過治療的晚期pNEt和晚期epNEt的sNDA的監管審查過程，包括FDA指定的處方藥用戶費法案目標行動日期；以及Exelixis追求創造具有轉化性治療潛力的科學努力，爲患者提供更多未來希望。任何涉及對未來事件或情況的期望、預測或其他描述的聲明都是前瞻性聲明，基於Exelixis當前的計劃、假設、信念、期望、估計和投射。前瞻性聲明涉及風險和不確定性。由於這些風險和不確定性，實際結果和事件的時間可能與前瞻性聲明中預期的結果有實質不同。這些風險和不確定性包括但不限於：美國和其他地方監管審查和批准過程的複雜性和不可預測性，包括FDA可能不會及時批准卡波替尼用於治療pNEt或epNEt，甚至可能不批准的風險；可能由於出現不良安全事件或對評估卡波替尼的臨床試驗的額外數據分析而出現的意外問題；Exelixis保護其知識產權的能力；市場競爭，包括競爭對手可能獲得通用版本CABOMETYX的批准的潛力；經濟和商業條件的變化；以及影響Exelixis獲得卡波替尼在新適應症中監管批准能力的其他因素，這些因素從時間到時間在Exelixis的最新年度10-k表格的「風險因素」標題下以及以後的季度10-Q表格中詳細闡述，並在Exelixis將來向證券交易委員會提交的文件中。本新聞稿中的所有前瞻性聲明基於Exelixis截至本新聞稿日期的信息，Exelixis無義務更新或修訂本處包含的任何前瞻性聲明，除非法律要求。
Exelixis, the Exelixis logo and CABOMETYX are registered U.S. trademarks of Exelixis.
伊克力西斯、伊克力西斯公司商標和CABOMETYX爲伊克力西斯的註冊美國商標。
______________________________
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.神經內分泌腫瘤。克利夫蘭診所網站。網址：。2024年11月查看。
2 人口估計：不可切除、局部進展或轉移性非胰腺外 NEt。 2024 年 6 月（內部文件）。
3 Pathak，S.，Starr，J.S.，Halfdanarson t.等。了解神經內分泌腫瘤不斷增加的原因。專業評論內分泌代謝。2023年9月；18(5)：377-385。
4.胰腺神經內分泌腫瘤（島細胞腫瘤）治療（PDQ）- 患者版本。NCI網站。網址：。2024年11月查看。
5.什麼是胰腺神經內分泌腫瘤？ ACS網站。網址：。2024年11月查看。
6 McClellan萬。，Chen。E.Y，Kardosh A.等。治療耐藥的胃腸胰神經內分泌腫瘤。癌症。2022年，14(19)，4769。
7 什麼是胃腸類癌症腫瘤? 美國癌症協會網站。網址：。2024 年 11 月訪問。
8 胃腸類癌症腫瘤的存活率。美國癌症協會網站。網址：。2024 年 11 月訪問。
9 肺類癌症腫瘤的存活率。美國癌症協會網站。網址：。2024 年 11 月訪問。
10 胰腺神經內分泌腫瘤的存活率。美國癌症協會網站。網址：。2024 年 11 月訪問。
11 神經內分泌腫瘤 (NET)。新華保險網站。網址：。2024 年 11 月訪問。
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
投資者聯繫方式：
蘇珊·哈伯德
公共事務和EVP
投資者關係
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
媒體聯繫：
lindsay Treadway
副總裁，公共事務和倡導關係
伊克力西斯股份有限公司
(650) 837-7522
ltreadway@exelixis.com
Source: Exelixis, Inc.
來源：伊克力西斯股份有限公司。
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