Libtayo（cemiplimab-rwlc）静脉注射液-为全球第六款PD-(L)1肿瘤免疫疗法。

2018年9月29日，法国药企赛诺菲(Sanofi)与再生元(Regeneron)宣布，双方联合研制的PD-1肿瘤免疫疗法Libtayo（cemiplimab-rwlc）静脉注射液获美国FDA批准用于转移性皮肤鳞状细胞癌（CSCC）或局部晚期CSCC治疗，适用于不能实施治愈性手术或治愈性放疗的患者。这是FDA批准的首个专门用于晚期CSCC的药物。Libtayo通过靶向细胞通路PD-1（在人体免疫细胞及某些癌细胞发现的蛋白质）而发挥作用。该药物通过阻断这一通路，可以帮助人体免疫系统抗击癌细胞。
  FDA药物评价与研究中心血液及肿瘤产品办公室代理主任兼FDA肿瘤优化中心主任Pazdur称：我们将继续看到肿瘤学领域朝着识别和开发针对特定分子靶点的药物转变。
  随着Libtayo的获批，FDA已经批准了6款靶向PD-1/PD-L1通路的免疫检查点抑制剂，用于治疗从膀胱癌到头颈癌等各种肿瘤，到现在可以治疗CSCC。这种肿瘤到了晚期可能难以有效地治疗，重要的是我们继续为患者带来了新的治疗方案。
  CSCC是美国第二大常见人类癌症，预计每年的发病率大约有70万例。最常见形式的皮肤癌是基底细胞癌。鳞状细胞属扁平细胞，看起来像鱼鳞，被发现于皮肤表面的组织中。CSCC 通常发生于经常暴露于阳光或其他紫外线辐射的皮肤部位。虽然大多数CSCC患者可以通过手术切除得到治愈，但少数患者将发展成晚期疾病，不再对手术及放疗等局部治疗有响应。晚期 CSCC会引起肿瘤部位毁容及局部并发症，如出血或感染，或者肿瘤扩散（转移）到局部淋巴结、远端组织及器官，从而变得有生命威胁。
  Libtayo的安全性与有效性基于两项开放标签临床试验。有效性评价总共涉及108名患者（75 名转移性疾病及33名局部晚期疾病）。这项研究的主要终点是客观缓解率，即治疗后肿瘤经历部分缩小或完全消失的患者比例。结果显示，所有以Libtayo治疗的患者，47.2%的人其肿瘤缩小或消失。大多数患者在数据分析时有持续的响应。
  Libtayo的常见副作用有疲劳、皮疹及腹泻。Libtayo在分发时必须配上一份描述药物使用及其严重警告的患者药物指南。Libtayo可导致免疫系统攻击人体任何部位正常的器官和组织，可影响它们的功能。这些副作用有时会变得严重或危及生命，可导致死亡。这些副作用包括免疫介导的副作用风险，如肺癌问题（肺炎）、肠道问题（结肠炎）、肝脏问题（肝炎）、分泌腺问题（内分泌）、皮肤（皮肤病）问题及肾脏问题。另外也应该监测患者的输注相关反应。
  Libtayo可以对发育中的胎儿造成伤害；妇女应该被告知该药物对胎儿的潜在风险，并使用有效的避孕措施FDA授予了该药物上市申请突破性疗法资格及优先审评资格。

Libtayo(Cemiplimab-rwlc Injection)
LIBTAYO is indicated for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation.
Important Safety Information
WARNINGS AND PRECAUTIONS
Severe and Fatal Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and usually occur during treatment; however, they can also occur after discontinuation. Early identification and management are essential to ensuring safe use of PD-1–blocking antibodies. Monitor for symptoms and signs of immune-mediated adverse reactions. Evaluate clinical chemistries, including liver tests and thyroid function tests, at baseline and periodically during treatment. Institute medical management promptly to include specialty consultation as appropriate.
In general, withhold LIBTAYO for Grade 3 or 4 and certain Grade 2 immune-mediated adverse reactions. Permanently discontinue LIBTAYO for Grade 4 and certain Grade 3 immune-mediated adverse reactions. For Grade 3 or 4 and certain Grade 2 immune-mediated adverse reactions, administer corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) or other appropriate therapy until improvement to Grade 1 or less followed by a corticosteroid taper over 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids. Institute hormone replacement therapy for endocrinopathies as warranted.
Immune-mediated pneumonitis: Immune-mediated pneumonitis occurred in 2.4% of 534 patients receiving LIBTAYO, including Grade 5 (0.2%), Grade 3 (0.7%), and Grade 2 (1.3%). Pneumonitis led to permanent discontinuation of LIBTAYO in 1.3% of patients. Systemic corticosteroids were required in all patients with pneumonitis, including 85% who received prednisone ≥40 mg/day or equivalent. Pneumonitis resolved in 62% of patients. Withhold LIBTAYO for Grade 2, and permanently discontinue for Grade 3 or 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper.
Immune-mediated colitis: Immune-mediated colitis occurred in 0.9% of 534 patients receiving LIBTAYO, including Grade 3 (0.4%) and Grade 2 (0.6%). Colitis led to permanent discontinuation of LIBTAYO in 0.2% of patients. Systemic corticosteroids were required in all patients with colitis, including 60% who received prednisone ≥40 mg/day or equivalent. Colitis resolved in 80% of patients. Withhold LIBTAYO for Grade 2 or 3, and permanently discontinue for Grade 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper.
Immune-mediated hepatitis: Immune-mediated hepatitis occurred in 2.1% of 534 patients receiving LIBTAYO, including Grade 5 (0.2%), Grade 4 (0.2%), and Grade 3 (1.7%). Hepatitis led to permanent discontinuation of LIBTAYO in 0.9% of patients. Systemic corticosteroids were required in all patients with hepatitis, including 91% who received prednisone ≥40 mg/day or equivalent. Hepatitis resolved in 64% of patients. Withhold LIBTAYO if AST or ALT increases to more than 3 and up to 10 times the upper limit of normal (ULN) or if total bilirubin increases up to 3 times the ULN. Permanently discontinue LIBTAYO if AST or ALT increases to more than 10 times the ULN or total bilirubin increases to more than 3 times the ULN. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper.
Immune-mediated endocrinopathies: Withhold LIBTAYO if clinically necessary for Grade 2, 3, or 4.
Adrenal insufficiency: Adrenal insufficiency occurred in 0.4% of 534 patients receiving LIBTAYO, including Grade 3 (0.2%) and Grade 2 (0.2%)
Hypophysitis: Hypophysitis, which can result in hypopituitarism, occurred in 0.2% of 534 patients receiving LIBTAYO, which consisted of 1 patient with Grade 3 hypophysitis
Hypothyroidism: Hypothyroidism occurred in 6% of 534 patients receiving LIBTAYO, including Grade 3 (0.2%) and Grade 2 (5.6%); no patients discontinued hormone replacement therapy
Hyperthyroidism: Hyperthyroidism occurred in 1.5% of 534 patients receiving LIBTAYO, including Grade 3 (0.2%) and Grade 2 (0.4%); hyperthyroidism resolved in 38% of patients
Type 1 diabetes mellitus: Type 1 diabetes mellitus, which can present with diabetic ketoacidosis, occurred in 0.7% of 534 patients, including Grade 4 (0.4%) and Grade 3 (0.4%); type 1 diabetes mellitus led to permanent discontinuation of LIBTAYO in 0.2% of patients
Immune-mediated nephritis with renal dysfunction: Immune-mediated nephritis occurred in 0.6% of 534 patients receiving LIBTAYO, including Grade 3 (0.4%) and Grade 2 (0.2%). Nephritis led to permanent discontinuation of LIBTAYO in 0.2% of patients. Systemic corticosteroids were required in all patients with nephritis, including 67% who received prednisone ≥40 mg/day or equivalent. Nephritis resolved in all patients. Withhold LIBTAYO for Grade 3, and permanently discontinue for Grade 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper.
Immune-mediated dermatologic adverse reactions: Immune-mediated dermatologic reactions, including erythema multiforme and pemphigoid, occurred in 1.7% of 534 patients receiving LIBTAYO, including Grade 3 (1.1%) and Grade 2 (0.6%). In addition, SJS and TEN have been observed with LIBTAYO and with other products in this class. Systemic corticosteroids were required in all patients with dermatologic reactions, including 89% who received prednisone ≥40 mg/day or equivalent. Dermatologic reactions resolved in 33% of patients. Approximately 22% of patients had recurrence of dermatologic reactions after re-initiation of LIBTAYO. Withhold LIBTAYO for Grade 3, and permanently discontinue for Grade 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper.
Other immune-mediated adverse reactions: The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% in 534 patients who received LIBTAYO or were reported with the use of other PD-1–blocking and PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions. Withhold LIBTAYO for Grade 3, and permanently discontinue for Grade 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper.
Neurological: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, and autoimmune neuropathy
Cardiovascular: Myocarditis, pericarditis, and vasculitides
Ocular: Uveitis, iritis, and other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various Grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss
Gastrointestinal: Pancreatitis to include increases in serum amylase and lipase levels, gastritis, and duodenitis
Musculoskeletal and connective tissue: Myositis, rhabdomyolysis, and associated sequelae, including renal failure, arthritis, and polymyalgia rheumatica
Hematological and immunological: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, and solid organ transplant rejection
Infusion-related reactions
Severe infusion-related reactions (Grade 3) occurred in 0.2% of patients receiving LIBTAYO. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or 2, and permanently discontinue for Grade 3 or.
Embryo-fetal toxicity
LIBTAYO can cause fetal harm when administered to a pregnant woman due to an increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LIBTAYO and for at least 4 months after the last dose.
Adverse reactions
Serious adverse reactions occurred in 28% of patients. Serious adverse reactions that occurred in ≥2% of patients were cellulitis, sepsis, pneumonia, pneumonitis, and urinary tract infection. The most common Grade 3-4 adverse reactions (≥2%) were cellulitis, sepsis, hypertension, pneumonia, musculoskeletal pain, skin infection, urinary tract infection, and fatigue
LIBTAYO was permanently discontinued due to adverse reactions in 5% of patients; adverse reactions resulting in permanent discontinuation were pneumonitis, autoimmune myocarditis, hepatitis, aseptic meningitis, complex regional pain syndrome, cough, and muscular weakness
The most common adverse reactions (incidence ≥20%) were fatigue, rash, and diarrhea