近日，德国默克（Merck KGaA）与辉瑞（Pfizer）共同宣布，美国FDA已批准其开发的BAVENCIO®（avelumab）注射液用于治疗晚期或转移性尿路上皮癌（UC）患者，患者之前接受过铂类化疗，或者接受铂类化疗作为新辅助治疗或辅助治疗后12个月内疾病进展。
  BAVENCIO先前已获得FDA的加速批准，用于治疗患有转移性Merkel细胞癌（MCC）的成人和12周岁以上儿童患者。“BAVENCIO获得批准用于治疗晚期或转移性尿路上皮癌患者，显示了我们为治疗最具挑战性的癌症寻找新疗法坚定不移的决心，”德国默克执行副总裁、全球生物制药业务研究与开发负责人Luciano Rossetti博士表示：“在获批治疗转移性Merkel细胞癌后的几周内，我们继续表现出了为有需求的患者加快获得创新药物的能力。”

   这一批准建立在BAVENCIO正在进行的尿路上皮癌临床研究项目的基础上，更加体现了我们对难治性癌症患者提供新药的承诺，”辉瑞肿瘤部的全球总裁Liz Barrett女士表示：“基于合作联盟的力量，以及辉瑞在泌尿生殖道癌症方面的丰富经验，我们认为BAVENCIO将是一个重要的治疗方案，希望这将有助于改善这些患者的治疗效果。”
  膀胱癌占尿路上皮癌的约90％，是美国第六大常见癌症。当肿瘤发生转移时，五年期生存率仅为5％。尽管晚期或转移性尿路上皮癌的疗法已经有所进展，但患者的预后仍然很差，需要更多的治疗方案。BAVENCIO中的活性成分avelumab为全人源化的PD-L1单抗，参与获得性免疫和先天免疫反应。通过结合PD-L1，BAVENCIO可以防止癌细胞使用PD-L1来逃避免疫细胞的抗肿瘤反应，激活白细胞（如T细胞）参与杀伤肿瘤。在体外实验中，BVENCIO还显示出诱导抗体依赖性细胞介导的细胞毒性（ADCC）的功能。“当接受化疗后的尿路上皮癌发生进展后，五年期生存率就会变得惊人的低，”美国国家癌症研究所（National Cancer Institute）的Andrea Apolo博士说：“直到最近，尿路上皮癌治疗领域的创新仍旧有限，这一批准提供给了我们另一种治疗方法，来帮助克服这种侵袭性疾病。
Bavencio(Avelumab Injection)
BAVENCIO Rx
Generic Name and Formulations:
Avelumab 20mg/mL; soln for IV infusion after dilution; preservative-free; contains mannitol.
Company:
EMD Serono, Inc.
Select therapeutic use: Bladder, kidney, and other urologic cancers
Melanoma and other skin cancers
Indications for BAVENCIO:
Treatment of locally advanced or metastatic urothelial carcinoma (UC) in patients who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
Adult:
Premedicate with an antihistamine and acetaminophen prior to the first 4 infusions; then subsequent doses as clinically indicated. Give as IV infusion over 60mins. 10mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.
Children:
<12yrs: not established.
Warnings/Precautions:
See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for Grade 3/4 pneumonitis or recurrent Grade 2 pneumonitis, Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis, AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, any life-threatening (Grade 4) or recurrent severe (Grade 3) immune-mediated adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2/3 immune-mediated adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2/3 diarrhea or colitis, Grade 3/4 adrenal insufficiency, Grade 3/4 thyroid disorders, Grade 3/4 hyperglycemia, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN; withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if Grade 1/2 infusion-related reactions occur; permanently discontinue if Grade 3/4. Monitor for abnormal liver tests, adrenal insufficiency, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥1 month after final dose. Pregnancy. Nursing mothers: not recommended (during and for ≥1 month after final dose).
Pharmacological Class:
Programmed death-ligand 1 (PD-L1) blocking antibody.
Adverse Reactions:
Fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, peripheral edema, UTI; other immune-mediated adverse reactions (may be fatal).
Generic Availability:
NO
How Supplied:
Single-dose vial (10mL)—1
Indications for BAVENCIO:
Treatment of metastatic Merkel cell carcinoma (MCC).
Adult:
Premedicate with an antihistamine and acetaminophen prior to the first 4 infusions; then subsequent doses as clinically indicated. Give as IV infusion over 60mins. 10mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.
Children:
<12yrs: not established.
Warnings/Precautions:
See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for Grade 3/4 pneumonitis or recurrent Grade 2 pneumonitis, Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis, AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, any life-threatening (Grade 4) or recurrent severe (Grade 3) immune-mediated adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2/3 immune-mediated adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2/3 diarrhea or colitis, Grade 3/4 adrenal insufficiency, Grade 3/4 thyroid disorders, Grade 3/4 hyperglycemia, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN; withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if Grade 1/2 infusion-related reactions occur; permanently discontinue if Grade 3/4. Monitor for abnormal liver tests, adrenal insufficiency, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥1 month after final dose. Pregnancy. Nursing mothers: not recommended (during and for ≥1 month after final dose).
Pharmacological Class:
Programmed death-ligand 1 (PD-L1) blocking antibody.
Adverse Reactions:
Fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, peripheral edema, UTI; other immune-mediated adverse reactions (may be fatal).
Generic Availability:
NO
How Supplied:
Single-dose vial (10mL)—1