温馨提醒：本说明书仅供参考，最新的说明书详见药品附带的说明书。

完整的处方信息

1 适应症和用法

LUMAKRAS 适用于治疗KRAS G12C突变的局部晚期或转移性非小细胞肺癌 (NSCLC)成人患者，由 FDA 批准的测试确定[见剂量和给药方法 (2.1) ]，他们已接受至少一种既往全身治疗。

该适应症在基于总体反应率 (ORR) 和反应持续时间 (DOR) 的加速批准下获得批准[见临床研究 (14) ]。对该适应症的持续批准可能取决于验证性试验中对临床益处的验证和描述。

2 剂量和给药方法

2.1 患者选择

根据肿瘤或血浆标本中KRAS G12C突变的存在，选择使用 LUMAKRAS 治疗局部晚期或转移性 NSCLC 的患者[参见临床研究 (14) ]。如果在血浆标本中未检测到突变，则测试肿瘤组织。

有关 FDA 批准的用于检测KRAS G12C突变的测试的信息，请访问：http: //www.fda.gov/CompanionDiagnostics。

2.2 推荐剂量和给药方法

LUMAKRAS 的推荐剂量为每天一次口服 960 毫克（8 片 120 毫克片剂），直至疾病进展或出现不可接受的毒性。

每天在同一时间服用或不服用 LUMAKRAS [见临床药理学 (12.3) ]。整片吞服。不要咀嚼、压碎或分割药片。如果漏服一剂 LUMAKRAS 超过 6 小时，请在第二天按照规定服用下一剂。不要同时服用 2 剂来弥补错过的剂量。

如果服用 LUMAKRAS 后发生呕吐，请勿服用额外剂量。第二天按照规定服用下一剂。

对吞咽固体有困难的患者的给药

将片剂分散在 120 毫升（4 盎司）非碳酸的室温水中，无需压碎。不得使用其他液体。搅拌直至片剂分散成小块（片剂不会完全溶解）并立即或在 2 小时内饮用。混合物的外观可以从淡黄色到亮黄色。吞下片剂分散液。不要咀嚼片剂的碎片。用另外 120 毫升（4 盎司）的水和饮料冲洗容器。如果混合物没有立即消耗，再次搅拌混合物以确保片剂分散。

2.3 不良反应的剂量调整

LUMAKRAS 剂量减少水平总结在表 1 中。表 2 中提供了不良反应的剂量调整。

如果发生不良反应，最多允许减少两次剂量。如果患者不能耐受每天一次 240 mg 的最小剂量，则终止 LUMAKRAS。

2.4 LUMAKRAS 与酸还原剂的共同给药

避免质子泵抑制剂 (PPI) 和 H 2受体拮抗剂与 LUMAKRAS共同给药。如果不能避免用减酸剂治疗，在给予局部抗酸剂前 4 小时或后 10 小时服用 LUMAKRAS [见药物相互作用 (7.1)和临床药理学 (12.3) ]。

3 剂型和规格

片剂：120 毫克，黄色，长方形，立即释放，薄膜包衣，一侧凹有“AMG”，另一侧凹有“120”。

4 禁忌症

没有任何。

5 警告和注意事项

5.1 肝毒性

LUMAKRAS 可引起肝毒性，可能导致药物性肝损伤和肝炎。在 CodeBreaK 100 [见不良反应 (6.1) ] 中接受 LUMAKRAS 的 357 名患者中，肝毒性发生率为 1.7%（所有级别）和 1.4%（3 级）。总共有 18% 接受 LUMAKRAS 的患者出现丙氨酸转氨酶 (ALT) 升高/天冬氨酸转氨酶 (AST) 升高；6% 为 3 级，0.6% 为 4 级。首次出现 ALT/AST 升高的中位时间为 9 周（范围：0.3 至 42）。7% 的患者出现 ALT/AST 升高导致剂量中断或减少。由于 2.0% 的患者 ALT/AST 增加，LUMAKRAS 被终止。除了中断或减少剂量外，5% 的患者还接受了皮质类固醇治疗肝毒性。

在 LUMAKRAS 开始前监测肝功能测试（ALT、AST 和总胆红素），治疗的前 3 个月每 3 周监测一次，然后每月一次或根据临床指征监测，对出现转氨酶和转氨酶的患者进行更频繁的检测。 /或胆红素升高。根据不良反应的严重程度扣留、减少剂量或永久停用 LUMAKRAS [见剂量和给药方法 (2.3)和不良反应 (6.1) ]。

5.2 间质性肺病 (ILD)/肺炎

LUMAKRAS 可导致可能致命的 ILD/肺炎。在 CodeBreaK 100 中接受 LUMAKRAS 的 357 名患者中[见不良反应 (6.1) ]， 0.8% 的患者发生 ILD/肺炎，所有病例在发病时均为 3 或 4 级，1 例是致命的。ILD/肺炎首次发病的中位时间为 2 周（范围：2 至 18 周）。0.6% 的患者因 ILD/肺炎而停用 LUMAKRAS。监测患者是否出现新的或恶化的提示 ILD/肺炎的肺部症状（例如，呼吸困难、咳嗽、发烧）。在疑似 ILD/肺炎患者中立即不给 LUMAKRAS 和如果没有发现 ILD/肺炎的其他潜在原因永久终止 LUMAKRAS [见剂量和给药方法(2.3)和不良反应 (6.1) ]。

6 不良反应

在说明书的其他部分更详细地讨论了以下临床上显着的不良反应：

• 肝毒性[见警告和注意事项(5.1) ]
• 间质性肺病(ILD)/肺炎[见警告和注意事项(5.2) ]

6.1 临床试验经验

因为临床试验是在广泛不同的条件下进行的，在一种药物的临床试验中观察到的不良反应率不能直接与另一种药物临床试验中的发生率进行比较，并且可能无法反映实践中观察到的发生率。

警告和注意事项中描述的汇总安全性人群反映了在 CodeBreaK 100 中登记的357 名 NSCLC 和其他具有KRAS G12C突变的实体瘤患者中，每天一次口服 960 毫克的LUMAKRAS，28% 的患者暴露了 6 个月或更长的时间和 3% 的暴露时间超过一年。

非小细胞肺癌

在 CodeBreaK 100 中，在KRAS G12C突变的局部晚期或转移性 NSCLC患者的亚组中评估了 LUMAKRAS 的安全性[参见临床研究 (14) ]。患者每天一次口服 LUMAKRAS 960 mg，直至疾病进展或出现不可接受的毒性（n = 204）。在接受 LUMAKRAS 治疗的患者中，39% 的患者暴露时间为 6 个月或更长时间，3% 的患者暴露时间超过一年。

接受 LUMAKRAS 治疗的患者的中位年龄为 66 岁（范围：37 至 86 岁）；55% 女性；80% 白人、15% 亚洲人和 3% 黑人。

50% 接受 LUMAKRAS 治疗的患者发生严重不良反应。≥ 2% 患者的严重不良反应为肺炎 (8%)、肝毒性 (3.4%) 和腹泻 (2%)。由于呼吸衰竭（0.8%）、肺炎（0.4%）、心脏骤停（0.4%）、心力衰竭（0.4%）、胃溃疡（0.4%）和肺炎，接受 LUMAKRAS 治疗的患者中有 3.4% 发生致命不良反应(0.4%)。

9% 的患者因不良反应而永久停用 LUMAKRAS。导致 ≥ 2% 患者永久终止 LUMAKRAS 的不良反应包括肝毒性 (4.9%)。

34% 的患者因不良反应而中断 LUMAKRAS 的剂量。≥ 2% 的患者需要中断剂量的不良反应为肝毒性 (11%)、腹泻 (8%)、肌肉骨骼疼痛 (3.9%)、恶心 (2.9%) 和肺炎 (2.5%)。

5% 的患者因不良反应而降低 LUMAKRAS 的剂量。≥ 2% 的患者需要减少剂量的不良反应包括 ALT (2.9%) 和 AST (2.5%) 升高。

最常见的不良反应 (≥ 20%) 是腹泻、肌肉骨骼疼痛、恶心、疲劳、肝毒性和咳嗽。最常见的实验室异常（≥ 25%）是淋巴细胞减少、血红蛋白减少、天冬氨酸转氨酶增加、丙氨酸转氨酶增加、钙减少、碱性磷酸酶增加、尿蛋白增加和钠减少。

表 3 总结了 CodeBreaK 100 中观察到的常见不良反应。

表 4 总结了 CodeBreaK 100 中观察到的选定实验室不良反应。

7 药物相互作用

7.1 其他药物对 LUMAKRAS 的影响

酸还原剂

LUMAKRAS 与胃酸减少剂的共同给药降低了索托拉西的浓度[见临床药理学 (12.3) ]，这可能会降低索托拉西的疗效。避免 LUMAKRAS 与质子泵抑制剂 (PPI)、H 2受体拮抗剂和局部作用抗酸剂共同给药。如果不能避免与酸减少剂共同给药，在局部作用的抗酸剂给药前 4 小时或后 10 小时给予 LUMAKRAS [见剂量和给药方法 (2.4) ]。

强 CYP3A4 诱导剂

LUMAKRAS 与强 CYP3A4 诱导剂的共同给药降低了sotorasib浓度[见临床药理学 (12.3) ]，这可能会降低sotorasib的疗效。避免 LUMAKRAS 与强 CYP3A4 诱导剂共同给药。

7.2 LUMAKRAS 对其他药物的影响

CYP3A4 底物

LUMAKRAS 与 CYP3A4 底物共同给药降低其血浆浓度[见临床药理学 (12.3) ]，这可能会降低底物的功效。避免 LUMAKRAS 与 CYP3A4 敏感底物共同给药，因为最小的浓度变化可能导致底物的治疗失败。如果不能避免共同给药，请根据其处方信息增加敏感的 CYP3A4 底物剂量。

P-糖蛋白 (P-gp) 底物

LUMAKRAS 与 P-gp 底物（地高辛）共同给药增加地高辛血浆浓度[见临床药理学 (12.3) ]，这可能增加地高辛的不良反应。避免将 LUMAKRAS 与 P-gp 底物共同给药，因为最小的浓度变化可能会导致严重的毒性。如果无法避免共同给药，请根据其处方信息减少 P-gp 底物剂量。

8 在特定人群中的使用

8.1 怀孕

风险总结

没有关于孕妇使用 LUMAKRAS 的可用数据。在大鼠和兔胚胎-胎儿发育研究中，口服索托拉西在高达 960 mg 临床剂量人类暴露量的 4.6 倍时不会导致不利的发育影响或胚胎致死性（见数据）。

在美国一般人群中，临床认可的妊娠中主要出生缺陷和流产的估计背景风险分别为 2% 至 4% 和 15% 至 20%。

数据

动物数据

在一项大鼠胚胎-胎儿发育研究中，在器官形成期对怀孕大鼠每天一次口服索托拉西导致母体毒性在 540 mg/kg 剂量水平（根据曲线下面积（AUC）约为人类暴露的 4.6 倍） ) 临床剂量为 960 毫克)。在高达 540 mg/kg 的剂量下，Sotorasib不会导致不利的发育影响并且不会影响胚胎-胎儿存活。

在一项兔胚胎-胎儿发育研究中，在器官形成期间每天一次口服索托拉西导致胎儿体重降低和胎儿骨化掌骨数量在 100 mg/kg 剂量水平减少（约 2.6 倍）人类暴露基于临床剂量 960 mg 的 AUC），这与母体毒性相关，包括给药阶段体重增加减少和食物消耗减少。在高达 100 mg/kg 的剂量下，Sotorasib不会导致不利的发育影响并且不会影响胚胎-胎儿存活。

8.2 泌乳

风险总结

没有关于人乳汁中索托拉西或其代谢物的存在、对母乳喂养儿童的影响或对产奶量的数据。由于母乳喂养儿童可能出现严重不良反应，建议妇女在用 LUMAKRAS 治疗期间和最后一次给药后 1 周内不要母乳喂养。

8.4 儿科使用

LUMAKRAS 在儿科患者中的安全性和有效性尚未确定。

8.5 老年人使用

在 CodeBreaK 100 中每天一次口服 LUMAKRAS 960 mg 的 357 名任何肿瘤类型的患者中，46% 为 65 岁及以上，10% 为 75 岁及以上。在老年患者和年轻患者之间未观察到安全性或有效性的总体差异。

11 说明

Sotorasib是 RAS GTPase 家族的抑制剂。分子式为C 30 H 30 F 2 N 6 O 3，分子量为560.6 g/mol。索托拉西的化学名称为 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4 -[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one。

索托拉西的化学结构如下图所示：

Sotorasib 的pKa 值为 8.06 和 4.56。索托拉西在水性介质中的溶解度在 pH 1.2 至 6.8 范围内从 1.3 mg/mL 降低至 0.03 mg/mL。

LUMAKRAS 以含有 120 mg sotorasib 的口服薄膜包衣片形式提供。片芯中的非活性成分是微晶纤维素、乳糖一水合物、交联羧甲基纤维素钠和硬脂酸镁。薄膜包衣材料由聚乙烯醇、二氧化钛、聚乙二醇、滑石粉和氧化铁黄组成。

12 临床药理学

12.1 作用机制

Sotorasib是 KRAS G12C的抑制剂，KRAS GTPase KRAS 是一种肿瘤限制性突变致癌形式。Sotorasib与 KRAS G12C的独特半胱氨酸形成不可逆的共价键，将蛋白质锁定在非活性状态，防止下游信号传导，而不会影响野生型 KRAS。Sotorasib仅在KRAS G12C肿瘤细胞系中阻断 KRAS 信号传导、抑制细胞生长并促进细胞凋亡。Sotorasib在体外和体内抑制 KRAS G12C ，可检测到的脱靶活性极低。在小鼠肿瘤异种移植模型中，索托拉西-治疗导致肿瘤消退和延长生存期，并与KRAS G12C模型中的抗肿瘤免疫有关。

12.2 药效学

Sotorasib暴露-反应关系和药效学反应的时间过程是未知的。

心脏电生理

在批准的推荐剂量下，LUMAKRAS 不会导致 QTc 间期（> 20 毫秒）的大幅平均增加。

12.3 药代动力学

索托拉西的药代动力学已在健康受试者和KRAS G12C突变实体瘤（包括 NSCLC）患者中表征。Sotorasib在 180 mg 至 960 mg（批准推荐剂量的 0.19 至 1 倍）的剂量范围内表现出非线性、时间依赖性、药代动力学，每天一次，全身暴露（即 AUC 0-24h和 C max）相似在稳态。Sotorasib全身暴露在薄膜包衣片和在禁食条件下预先分散在水中的薄膜包衣片之间相当。索托拉西布血浆浓度在 22 天内达到稳态。重复 LUMAKRAS 剂量后未观察到蓄积，平均蓄积率为 0.56（变异系数 (CV)：59%）。

吸收

达到索托拉西峰值血浆浓度的中位时间为 1 小时。

食物的作用

当960毫克LUMAKRAS用高脂肪，高热量的膳食（含有大约800〜1000卡路里150，250，和500至600分别从蛋白质，碳水化合物和脂肪，卡路里）患者给药，sotorasib AUC 0-24h与禁食条件下给药相比增加了 25%。

分配

稳态下的索托拉西平均分布容积 (V d ) 为 211 L (CV: 135%)。在体外，索托拉西血浆蛋白结合率为 89%。

消除

所述sotorasib平均终末消除半衰期为5小时（标准偏差（SD）：2）。每天一次 960 mg LUMAKRAS 时，索托拉西稳态表观清除率为 26.2 L/hr（CV：76%）。

代谢

索托拉西的主要代谢途径是与CYP3As的非酶结合和氧化代谢。

排泄

单剂量放射性标记的索托拉西后，粪便中回收了 74% 的剂量（53% 未改变），尿液中回收 6%（1% 未改变）。

特定人群

没有临床上的药代动力学有意义的差异sotorasib观察根据年龄（28〜86岁），性别，种族（白人，黑人和亚裔），体重（36.8到157.9公斤），治疗的线，ECOG PS（0， 1)、轻度和中度肾功能不全（eGFR：≥ 30 mL/min/1.73 m 2），或轻度肝功能不全（AST 或 ALT < 2.5 × ULN 或总胆红素 < 1.5 × ULN）。尚未研究严重肾损害或中度至重度肝损害对索托拉西药代动力学的影响。

药物相互作用研究

临床研究

酸减少剂：与LUMAKRAS单剂量的重复剂量奥美拉唑（PPI）的合用降低sotorasib Ç最大65％和AUC 57％进料的条件下，降低sotorasib Ç最大下由57％和AUC 42％禁食条件。在进食条件下，在单剂量 LUMAKRAS 之前 10 小时和之后 2 小时同时给予单剂量法莫替丁（H 2受体拮抗剂）使sotorasib C max降低 35% 和 AUC 降低 38% 。

强 CYP3A4 诱导剂：重复剂量的利福平（一种强 CYP3A4 诱导剂）与单剂 LUMAKRAS 共同给药使sotorasib C max降低 35%，AUC 降低 51%。

其他药物：否上的曝光临床上有意义的效果sotorasib观察以下伊曲康唑（组合的强CYP3A4及P-gp抑制剂）和利福平的单次剂量（一个OATP1B1 / 1B3抑制剂）或二甲双胍（一个MATE1 LUMAKRAS合用/MATE2-K 底物）。

CYP3A4 底物：LUMAKRAS 与咪达唑仑（一种敏感的 CYP3A4 底物）共同给药使咪达唑仑 C max降低 48%，AUC 降低 53%。

P-gp 底物：LUMAKRAS 与地高​​辛（一种 P-gp 底物）的共同给药使地高辛 C max增加了 91%，AUC 增加了 21%。

MATE1/MATE2-K 底物：在共同给药 LUMAKRAS 后，未观察到对二甲双胍（一种 MATE1/MATE2-K 底物）暴露量的临床意义影响。

体外研究

细胞色素 P450 (CYP)酶: Sotorasib可诱导 CYP2C8、CYP2C9 和 CYP2B6。索托拉西不抑制 CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19 或 CYP2D6。

转运系统：Sotorasib可能会抑制 BCRP。

13 非临床毒理学

13.1 致癌作用、诱变作用、生育力受损

尚未对索托拉西进行致癌性研究。

Sotorasib在体外细菌回复突变 (Ames) 试验中没有致突变性，在体内大鼠微核和彗星试验中没有遗传毒性。

未使用索托拉西进行生育力/早期胚胎发育研究。在对狗和大鼠进行的一般毒理学研究中，对雌性或雄性生殖器官没有不良影响。

13.2 动物毒理学和/或药理学

在大鼠中，肾毒性包括最小到显着的组织学肾小管变性/坏死和增加的肾重量、尿素氮、肌酐和肾小管损伤的尿生物标志物，其剂量导致暴露量约为人 AUC 临床剂量的 0.5 倍960 毫克。与人类相比，大鼠肾脏中半胱氨酸 S-缀合物 β-裂解酶途径代谢的增加可能使大鼠更容易受到肾毒性的影响，因为局部形成了一种假定的含硫代谢物，而不是人类。

在狗的 3 个月毒理学研究中，索托拉西在肝脏（小叶中心肝细胞肥大）、垂体（嗜碱性粒细胞肥大）和甲状腺（显着滤泡细胞萎缩、中度至显着胶体耗竭和滤泡细胞肥大）中引起发现根据临床剂量 960 mg 的 AUC，暴露量约为人体暴露量的 0.4 倍。这些发现可能是由于对肝细胞酶诱导的适应性反应和随后的甲状腺激素水平降低（即继发性甲状腺功能减退症）。尽管未在狗中测量甲状腺水平，但在体外狗肝细胞测定中证实了已知参与甲状腺激素代谢的尿苷二磷酸葡萄糖醛酸转移酶的诱导。

14 临床研究

LUMAKRAS 的疗效在参加单臂、开放标签、多中心试验 (CodeBreaK 100 [NCT03600883]) 的一部分患者中得到证实。符合条件的患者需要在接受免疫检查点抑制剂和/或铂类化疗后疾病进展的局部晚期或转移性KRAS G12C 突变非小细胞肺癌，东部肿瘤协作组表现状态 (ECOG PS) 为 0 或 1，并且在实体瘤反应评估标准 (RECIST v1.1) 定义的至少一个可测量的病变。

要求所有患者使用 QIAGEN therascreen ® KRAS RGQ PCR Kit 在中心实验室进行的肿瘤组织样本中前瞻性鉴定KRAS G12C突变的 NSCLC 。在总共 126 名登记受试者中，有 2 名 (2%) 由于基线时没有放射学可测量的病变而无法进行疗效分析。在肿瘤组织中确认有KRAS G12C突变的 124 名患者中，使用 Guardant360 ® CDx对来自 112 名患者的血浆样本进行了回顾性检测。78/112 名患者 (70%)在血浆标本中发现KRAS G12C突变，31/112 名患者 (28%) 没有KRAS G12C由于 Guardant360 ® CDx 测试失败，血浆样本中确定的突变和 3/112 (2%) 无法评估。

共有 124 名患者在基线时至少有一个可测量的病变，根据 RECIST v1.1 由盲法独立中央审查 (BICR) 评估，并每天接受一次 LUMAKRAS 960 mg 治疗，直至疾病进展或出现不可接受的毒性。根据 RECIST v1.1，由 BICR 评估的主要疗效结果指标是客观缓解率 (ORR) 和缓解持续时间 (DOR)。

研究人群的基线人口统计学和疾病特征为：中位年龄 64 岁（范围：37 至 80），48% ≥ 65 岁，8% ≥ 75 岁；50% 女性；82% 白人，15% 亚洲人，2% 黑人；70% ECOG PS 1; 96% 患有 IV 期疾病；99% 具有非鳞状组织学；81% 以前吸烟者，12% 现在吸烟者，5% 从不吸烟者。所有患者都接受了至少 1 种先前针对转移性 NSCLC 的全身治疗；43% 只接受过 1 线治疗，35% 接受过 2 线治疗，23% 接受过 3 线治疗；91% 既往接受过抗 PD-1/PD-L1 免疫治疗，90% 接受过基于铂的化疗，81% 接受过铂类化疗和抗 PD-1/PD-L1。已知的胸外转移部位包括 48% 的骨、21% 的脑和 21% 的肝脏。

功效结果总结在表5中。

16 如何供应/储存和处理

如何供应

LUMAKRAS ( sotorasib ) 120 毫克片剂为黄色，长方形，薄膜包衣，一侧凹有“AMG”，另一侧有“120”，供应如下：

• 装有两瓶 120 片的纸盒，带防儿童盖，NDC 55513-488-02
• 包含一瓶 240 片的纸箱，带有防儿童封口，NDC 55513-488-24

储存和处理

储存在 20°C 至 25°C（68°F 至 77°F）。允许在 15°C 至 30°C（59°F 至 86°F）之间进行远足[参见 USP 控制室温]。

17 患者咨询信息

建议患者阅读 FDA 批准的患者标签（患者信息）。

肝毒性

忠告患者立即联系他们的卫生保健提供者对肝功能障碍的体征和症状[见警告和注意事项(5.1) ]。

间质性肺病 (ILD)/肺炎

忠告患者立即联系他们的卫生保健提供者报告新的或恶化的呼吸道症状[见警告和注意事项(5.2) ]。

哺乳期

建议妇女在用 LUMAKRAS 治疗期间和最后一次给药后 1 周内不要母乳喂养[见特殊人群中的使用 (8.2) ]。

药物相互作用

建议患者将所有伴随药物告知其医疗保健提供者，包括处方药、非处方药、维生素、饮食和草药产品。告知患者在服用 LUMAKRAS 时避免使用质子泵抑制剂和 H 2受体拮抗剂[见药物相互作用 (7.1)和(7.2) ]。

如果不能避免与酸减少剂共同给药，告知患者在局部作用抗酸剂之前 4 小时或之后 10 小时服用 LUMAKRAS [见剂量和给药方法 (2.4) ]。

漏服

如果超过 6 小时错过了一个剂量的 LUMAKRAS，第二天按照规定恢复治疗[见剂量和给药方法 (2.2) ]。

LUMAKRAS ™（索托拉西）

制造商：
Amgen Inc.
One Amgen Center Drive
千橡市，CA 91320-1799 美国

专利：http://pat.amgen.com/lumakras/
© 2021 Amgen Inc. 保留所有权利。

1XXXXXX – V1

主要显示面板 - 120 毫克片剂瓶纸箱标签

NDC 55513-488-24

LUMAKRAS™
（索托拉西）片剂

120 毫克

每片含有 120 毫克索托拉西。

储存在 20°C 至 25°C（68°F 至 77°F）。
允许在 15°C 至 30°C
（59°F 至 86°F）之间进行短途旅行。

推荐剂量：见处方
信息。

安进®

【备注】以上内容仅供参考，不作为用药依据，详情请参照药品附带说明书。

本说明书来源于：美国FDA

https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/c80a362c-7ac3-4894-a076-0691e68ef8c1/spl-doc?hl=Sotorasib

温馨提醒：

①建议您用 谷歌浏览器  在电脑上或手机  打开以上链接，就可以自动翻译成简体中文，而且翻译的还比较准确。

②本说明书仅供参考，最新的说明书详见药品附带的说明书

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test [see Dosage and Administration (2.1)], who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR) [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Select patients for treatment of locally advanced or metastatic NSCLC with LUMAKRAS based on the presence of KRAS G12C mutation in tumor or plasma specimens [see Clinical Studies (14)]. If no mutation is detected in a plasma specimen, test tumor tissue.

Information on FDA-approved tests for the detection of KRAS G12C mutations is available at: http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dosage and Administration

The recommended dosage of LUMAKRAS is 960 mg (eight 120 mg tablets) orally once daily until disease progression or unacceptable toxicity.

Take LUMAKRAS at the same time each day with or without food [see Clinical Pharmacology (12.3)]. Swallow tablets whole. Do not chew, crush or split tablets. If a dose of LUMAKRAS is missed by more than 6 hours, take the next dose as prescribed the next day. Do not take 2 doses at the same time to make up for the missed dose.

If vomiting occurs after taking LUMAKRAS, do not take an additional dose. Take the next dose as prescribed the next day.

Administration to Patients Who Have Difficulty Swallowing Solids

Disperse tablets in 120 mL (4 ounces) of non-carbonated, room-temperature water without crushing. No other liquids should be used. Stir until tablets are dispersed into small pieces (the tablets will not completely dissolve) and drink immediately or within 2 hours. The appearance of the mixture may range from pale yellow to bright yellow. Swallow the tablet dispersion. Do not chew pieces of the tablet. Rinse the container with an additional 120 mL (4 ounces) of water and drink. If the mixture is not consumed immediately, stir the mixture again to ensure that tablets are dispersed.

2.3 Dosage Modifications for Adverse Reactions

LUMAKRAS dose reduction levels are summarized in Table 1. Dosage modifications for adverse reactions are provided in Table 2.

If adverse reactions occur, a maximum of two dose reductions are permitted. Discontinue LUMAKRAS if patients are unable to tolerate the minimum dose of 240 mg once daily.

2.4 Coadministration of LUMAKRAS with Acid-Reducing Agents

Avoid coadministration of proton pump inhibitors (PPIs) and H2 receptor antagonists with LUMAKRAS. If treatment with an acid-reducing agent cannot be avoided, take LUMAKRAS 4 hours before or 10 hours after administration of a local antacid [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Tablets: 120 mg, yellow, oblong-shaped, immediate release, film-coated, debossed with "AMG" on one side and "120" on the opposite side.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Among 357 patients who received LUMAKRAS in CodeBreaK 100 [see Adverse Reactions (6.1)], hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. The median time to first onset of increased ALT/AST was 9 weeks (range: 0.3 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 7% of patients. LUMAKRAS was discontinued due to increased ALT/AST in 2.0% of patients. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.

Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction [see Dosage and Administration (2.3) and Adverse Reactions (6.1)].

5.2 Interstitial Lung Disease (ILD)/Pneumonitis

LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100 [see Adverse Reactions (6.1)], ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 2 weeks (range: 2 to 18 weeks). LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.3) and Adverse Reactions (6.1)].

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

• Hepatotoxicity [see Warnings and Precautions (5.1)]
• Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to LUMAKRAS as a single agent at 960 mg orally once daily in 357 patients with NSCLC and other solid tumors with KRAS G12C mutation enrolled in CodeBreaK 100, 28% were exposed for 6 months or longer and 3% were exposed for greater than one year.

Non-Small Cell Lung Cancer

The safety of LUMAKRAS was evaluated in a subset of patients with KRAS G12C-mutated locally advanced or metastatic NSCLC in CodeBreaK 100 [see Clinical Studies (14)]. Patients received LUMAKRAS 960 mg orally once daily until disease progression or unacceptable toxicity (n = 204). Among patients who received LUMAKRAS, 39% were exposed for 6 months or longer and 3% were exposed for greater than one year.

The median age of patients who received LUMAKRAS was 66 years (range: 37 to 86); 55% female; 80% White, 15% Asian, and 3% Black.

Serious adverse reactions occurred in 50% of patients treated with LUMAKRAS. Serious adverse reactions in ≥ 2% of patients were pneumonia (8%), hepatotoxicity (3.4%), and diarrhea (2%). Fatal adverse reactions occurred in 3.4% of patients who received LUMAKRAS due to respiratory failure (0.8%), pneumonitis (0.4%), cardiac arrest (0.4%), cardiac failure (0.4%), gastric ulcer (0.4%), and pneumonia (0.4%).

Permanent discontinuation of LUMAKRAS due to an adverse reaction occurred in 9% of patients. Adverse reactions resulting in permanent discontinuation of LUMAKRAS in ≥ 2% of patients included hepatotoxicity (4.9%).

Dosage interruptions of LUMAKRAS due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥ 2% of patients were hepatotoxicity (11%), diarrhea (8%), musculoskeletal pain (3.9%), nausea (2.9%), and pneumonia (2.5%).

Dose reductions of LUMAKRAS due to an adverse reaction occurred in 5% of patients. Adverse reactions which required dose reductions in ≥ 2% of patients included increased ALT (2.9%) and increased AST (2.5%).

The most common adverse reactions (≥ 20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urine protein, and decreased sodium.

Table 3 summarizes the common adverse reactions observed in CodeBreaK 100.

Table 4 summarizes the selected laboratory adverse reactions observed in CodeBreaK 100.

7 DRUG INTERACTIONS

7.1 Effects of Other Drugs on LUMAKRAS

Acid-Reducing Agents

Coadministration of LUMAKRAS with gastric acid-reducing agents decreased sotorasib concentrations [see Clinical Pharmacology (12.3)], which may reduce the efficacy of sotorasib. Avoid coadministration of LUMAKRAS with proton pump inhibitors (PPIs), H2 receptor antagonists, and locally acting antacids. If coadministration with an acid-reducing agent cannot be avoided, administer LUMAKRAS 4 hours before or 10 hours after administration of a locally acting antacid [see Dosage and Administration (2.4)].

Strong CYP3A4 Inducers

Coadministration of LUMAKRAS with a strong CYP3A4 inducer decreased sotorasib concentrations [see Clinical Pharmacology (12.3)], which may reduce the efficacy of sotorasib. Avoid coadministration of LUMAKRAS with strong CYP3A4 inducers.

7.2 Effects of LUMAKRAS on Other Drugs

CYP3A4 Substrates

Coadministration of LUMAKRAS with a CYP3A4 substrate decreased its plasma concentrations [see Clinical Pharmacology (12.3)], which may reduce the efficacy of the substrate. Avoid coadministration of LUMAKRAS with CYP3A4 sensitive substrates, for which minimal concentration changes may lead to therapeutic failures of the substrate. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information.

P-glycoprotein (P-gp) Substrates

Coadministration of LUMAKRAS with a P-gp substrate (digoxin) increased digoxin plasma concentrations [see Clinical Pharmacology (12.3)], which may increase the adverse reactions of digoxin. Avoid coadministration of LUMAKRAS with P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If coadministration cannot be avoided, decrease the P-gp substrate dosage in accordance with its Prescribing Information.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on LUMAKRAS use in pregnant women. In rat and rabbit embryo-fetal development studies, oral sotorasib did not cause adverse developmental effects or embryo-lethality at exposures up to 4.6 times the human exposure at the 960 mg clinical dose (see Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In a rat embryo-fetal development study, once daily oral administration of sotorasib to pregnant rats during the period of organogenesis resulted in maternal toxicity at the 540 mg/kg dose level (approximately 4.6 times the human exposure based on area under the curve (AUC) at the clinical dose of 960 mg). Sotorasib did not cause adverse developmental effects and did not affect embryo-fetal survival at doses up to 540 mg/kg.

In a rabbit embryo-fetal development study, once daily oral administration of sotorasib during the period of organogenesis resulted in lower fetal body weights and a reduction in the number of ossified metacarpals in fetuses at the 100 mg/kg dose level (approximately 2.6 times the human exposure based on AUC at the clinical dose of 960 mg), which was associated with maternal toxicity including decreased body weight gain and food consumption during the dosing phase. Sotorasib did not cause adverse developmental effects and did not affect embryo-fetal survival at doses up to 100 mg/kg.

8.2 Lactation

Risk Summary

There are no data on the presence of sotorasib or its metabolites in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LUMAKRAS and for 1 week after the final dose.

8.4 Pediatric Use

The safety and effectiveness of LUMAKRAS have not been established in pediatric patients.

8.5 Geriatric Use

Of the 357 patients with any tumor type who received LUMAKRAS 960 mg orally once daily in CodeBreaK 100, 46% were 65 and over, and 10% were 75 and over. No overall differences in safety or effectiveness were observed between older patients and younger patients.

11 DESCRIPTION

Sotorasib is an inhibitor of the RAS GTPase family. The molecular formula is C30H30F2N6O3, and the molecular weight is 560.6 g/mol. The chemical name of sotorasib is 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-(1M)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2- methyl-4-(prop-2-enoyl)piperazin-1-yl]pyrido[2,3-d]pyrimidin-2(1H)-one.

The chemical structure of sotorasib is shown below:

Sotorasib has pKa values of 8.06 and 4.56. The solubility of sotorasib in the aqueous media decreases over the range pH 1.2 to 6.8 from 1.3 mg/mL to 0.03 mg/mL.

LUMAKRAS is supplied as film-coated tablets for oral use containing 120 mg of sotorasib. Inactive ingredients in the tablet core are microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, and magnesium stearate. The film coating material consists of polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide yellow.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Sotorasib is an inhibitor of KRASG12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRASG12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models, sotorasib-treatment led to tumor regressions and prolonged survival, and was associated with anti-tumor immunity in KRAS G12C models.

12.2 Pharmacodynamics

Sotorasib exposure-response relationships and the time course of the pharmacodynamic response are unknown.

Cardiac Electrophysiology

At the approved recommended dosage, LUMAKRAS does not cause large mean increases in the QTc interval (> 20 msec).

12.3 Pharmacokinetics

The pharmacokinetics of sotorasib have been characterized in healthy subjects and in patients with KRAS G12C-mutated solid tumors, including NSCLC. Sotorasib exhibited non-linear, time-dependent, pharmacokinetics over the dose range of 180 mg to 960 mg (0.19 to 1 time the approved recommended dosage) once daily with similar systemic exposure (i.e., AUC0-24h and Cmax) across doses at steady-state. Sotorasib systemic exposure was comparable between film-coated tablets and film-coated tablets predispersed in water administered under fasted conditions. Sotorasib plasma concentrations reached steady state within 22 days. No accumulation was observed after repeat LUMAKRAS dosages with a mean accumulation ratio of 0.56 (coefficient of variation (CV): 59%).

Absorption

The median time to sotorasib peak plasma concentration is 1 hour.

Effect of Food

When 960 mg LUMAKRAS was administered with a high-fat, high-calorie meal (containing approximately 800 to 1000 calories with 150, 250, and 500 to 600 calories from protein, carbohydrate and fat, respectively) in patients, sotorasib AUC0-24h increased by 25% compared to administration under fasted conditions.

Distribution

The sotorasib mean volume of distribution (Vd) at steady state is 211 L (CV: 135%). In vitro, sotorasib plasma protein binding is 89%.

Elimination

The sotorasib mean terminal elimination half-life is 5 hours (standard deviation (SD): 2). At 960 mg LUMAKRAS once daily, the sotorasib steady state apparent clearance is 26.2 L/hr (CV: 76%).

Metabolism

The main metabolic pathways of sotorasib are non-enzymatic conjugation and oxidative metabolism with CYP3As.

Excretion

After a single dose of radiolabeled sotorasib, 74% of the dose was recovered in feces (53% unchanged) and 6% (1% unchanged) in urine.

Specific Populations

No clinically meaningful differences in the pharmacokinetics of sotorasib were observed based on age (28 to 86 years), sex, race (White, Black and Asian), body weight (36.8 to 157.9 kg), line of therapy, ECOG PS (0, 1), mild and moderate renal impairment (eGFR: ≥ 30 mL/min/1.73 m2), or mild hepatic impairment (AST or ALT < 2.5 × ULN or total bilirubin < 1.5 × ULN). The effect of severe renal impairment or moderate to severe hepatic impairment on sotorasib pharmacokinetics has not been studied.

Drug Interaction Studies

Clinical Studies

Acid-Reducing Agents: Coadministration of repeat doses of omeprazole (PPI) with a single dose of LUMAKRAS decreased sotorasib Cmax by 65% and AUC by 57% under fed conditions, and decreased sotorasib Cmax by 57% and AUC by 42% under fasted conditions. Coadministration of a single dose of famotidine (H2 receptor antagonist) given 10 hours prior to and 2 hours after a single dose of LUMAKRAS under fed conditions decreased sotorasib Cmax by 35% and AUC by 38% .

Strong CYP3A4 Inducers: Coadministration of repeat doses of rifampin (a strong CYP3A4 inducer) with a single dose of LUMAKRAS decreased sotorasib Cmax by 35% and AUC by 51%.

Other Drugs: No clinically meaningful effect on the exposure of sotorasib was observed following coadministration of LUMAKRAS with itraconazole (a combined strong CYP3A4 and P-gp inhibitor) and a single dose of rifampin (an OATP1B1/1B3 inhibitor), or metformin (a MATE1/MATE2-K substrate).

CYP3A4 substrates: Coadministration of LUMAKRAS with midazolam (a sensitive CYP3A4 substrate) decreased midazolam Cmax by 48% and AUC by 53%.

P-gp substrates: Coadministration of LUMAKRAS with digoxin (a P-gp substrate) increased digoxin Cmax by 91% and AUC by 21%.

MATE1/MATE2-K substrates: No clinically meaningful effect on the exposure of metformin (a MATE1/MATE2-K substrate) was observed following coadministration of LUMAKRAS.

In Vitro Studies

Cytochrome P450 (CYP) Enzymes: Sotorasib may induce CYP2C8, CYP2C9 and CYP2B6. Sotorasib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6.

Transporter Systems: Sotorasib may inhibit BCRP.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with sotorasib.

Sotorasib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay and was not genotoxic in the in vivo rat micronucleus and comet assays.

Fertility/early embryonic development studies were not conducted with sotorasib. There were no adverse effects on female or male reproductive organs in general toxicology studies conducted in dogs and rats.

13.2 Animal Toxicology and/or Pharmacology

In rats, renal toxicity including minimal to marked histologic tubular degeneration/necrosis and increased kidney weight, urea nitrogen, creatinine, and urinary biomarkers of renal tubular injury were present at doses resulting in exposures approximately ≥ 0.5 times the human AUC at the clinical dose of 960 mg. Increases in cysteine S-conjugate β-lyase pathway metabolism in the rat kidney compared to human may make rats more susceptible to renal toxicity due to local formation of a putative sulfur-containing metabolite than humans.

In the 3-month toxicology study in dogs, sotorasib induced findings in the liver (centrilobular hepatocellular hypertrophy), pituitary gland (hypertrophy of basophils), and thyroid gland (marked follicular cell atrophy, moderate to marked colloid depletion, and follicular cell hypertrophy) at exposures approximately 0.4 times the human exposure based on AUC at the clinical dose of 960 mg. These findings may be due to an adaptive response to hepatocellular enzyme induction and subsequent reduced thyroid hormone levels (i.e. secondary hypothyroidism). Although thyroid levels were not measured in dogs, induction of uridine diphosphate glucuronosyltransferase known to be involved in thyroid hormone metabolism was confirmed in the in vitro dog hepatocyte assay.

14 CLINICAL STUDIES

The efficacy of LUMAKRAS was demonstrated in a subset of patients enrolled in a single-arm, open-label, multicenter trial (CodeBreaK 100 [NCT03600883]). Eligible patients were required to have locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy, an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1, and at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

All patients were required to have prospectively identified KRAS G12C-mutated NSCLC in tumor tissue samples by using the QIAGEN therascreen® KRAS RGQ PCR Kit performed in a central laboratory. Of 126 total enrolled subjects, 2 (2%) were unevaluable for efficacy analysis due to the absence of radiographically measurable lesions at baseline. Of the 124 patients with KRAS G12C mutations confirmed in tumor tissue, plasma samples from 112 patients were tested retrospectively using the Guardant360® CDx. 78/112 patients (70%) had KRAS G12C mutation identified in plasma specimen, 31/112 patients (28%) did not have KRAS G12C mutation identified in plasma specimen and 3/112 (2%) were unevaluable due to Guardant360® CDx test failure.

A total of 124 patients had at least one measurable lesion at baseline assessed by Blinded Independent Central Review (BICR) according to RECIST v1.1 and were treated with LUMAKRAS 960 mg once daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) as evaluated by BICR according to RECIST v1.1.

The baseline demographic and disease characteristics of the study population were: median age 64 years (range: 37 to 80) with 48% ≥ 65 years and 8% ≥ 75 years; 50% Female; 82% White, 15% Asian, 2% Black; 70% ECOG PS 1; 96% had stage IV disease; 99% with non-squamous histology; 81% former smokers, 12% current smokers, 5% never smokers. All patients received at least 1 prior line of systemic therapy for metastatic NSCLC; 43% received only 1 prior line of therapy, 35% received 2 prior lines of therapy, 23% received 3 prior lines of therapy; 91% received prior anti-PD-1/PD-L1 immunotherapy, 90% received prior platinum-based chemotherapy, 81% received both platinum-based chemotherapy and anti-PD-1/PD-L1. The sites of known extra-thoracic metastasis included 48% bone, 21% brain, and 21% liver.

Efficacy results are summarized in Table 5.

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

LUMAKRAS (sotorasib) 120 mg tablets are yellow, oblong-shaped, film-coated, debossed with "AMG" on one side and "120" on the opposite side are supplied as follows:

• Carton containing two bottles of 120 tablets with child-resistant closure, NDC 55513-488-02
• Carton containing one bottle of 240 tablets with child-resistant closure, NDC 55513-488-24

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Hepatotoxicity

Advise patients to immediately contact their healthcare provider for signs and symptoms of liver dysfunction [see Warnings and Precautions (5.1)].

Interstitial Lung Disease (ILD)/Pneumonitis

Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms [see Warnings and Precautions (5.2)].

Lactation

Advise women not to breastfeed during treatment with LUMAKRAS and for 1 week after the final dose [see Use in Specific Populations (8.2)].

Drug Interactions

Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products. Inform patients to avoid proton pump inhibitors, and H2 receptor antagonists while taking LUMAKRAS [see Drug Interactions (7.1) and (7.2)].

If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid [see Dosage and Administration (2.4)].

Missed Dose

If a dose of LUMAKRAS is missed by greater than 6 hours, resume treatment as prescribed the next day [see Dosage and Administration (2.2)].

LUMAKRAS™ (sotorasib)

Manufactured by:
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 U.S.A.

Patent: http://pat.amgen.com/lumakras/
© 2021 Amgen Inc. All rights reserved.

1XXXXXX – V1

PRINCIPAL DISPLAY PANEL - 120 mg Tablet Bottle Carton Label

NDC 55513-488-24

LUMAKRAS™
(sotorasib) TABLETS

120 mg

Each tablet contains 120 mg sotorasib.

Store at 20°C to 25°C (68°F to 77°F).
Excursions permitted from 15°C to 30°C
(59°F to 86°F).

Recommended Dosage: See Prescribing
Information.

AMGEN®

【备注】以上内容仅供参考，不作为用药依据，详情请参照药品附带说明书。