繼患者死亡後，FDA決定中止Advaxis的研究

2018年3月13日，Advaxis公司上市前交易的股價下跌超過21%，此前該公司宣布美國食品和藥物管理局（FDA）在1例患者死亡後，決定中止阿斯利康美國公司藥物的I/II期臨床試驗。

FDA中止了Advaxis公司axalimogene filolisbac和阿斯利康公司Imfinzi（durvalumab）的聯合研究。該聯合療法此前正用於晚期、複發性或難治性人乳頭瘤病毒（HPV）相關宮頸癌和HPV相關頭頸癌患者的臨床試驗。在2月底報道呼吸衰竭死亡事件後，監管機構於3月9日中止了該試驗。該公司表示，該患者的死亡發生在此次試驗的第6個聯合治療循環之後。

Advaxis公司的axalimogene filolisbac是一種有針對性的單核細胞增多性李斯特菌（Lm）的研究性免疫療法。該藥物使用活的減毒單核細胞增生利斯特氏菌（Lm）生物工程，在抗原呈遞細胞內產生和遞送腫瘤抗原/佐劑融合蛋白，產生強烈的T細胞介導的免疫。它正與阿斯利康公司的PD-1抑製劑Imfinzi聯用。Imfinzi已獲FDA批准用於不能手術切除腫瘤的非小細胞肺癌患者，以及一些膀胱癌患者。

Advaxis臨時首席執行官Anthony Lombardo表示，該公司密切關注參與試驗的患者及其安全，一旦成功，此項試驗將有望為晚期癌症開發新的治療方案。為了安撫投資者和業內人士，他補充道，公司相信其Lm技術有潛力開發這些治療方案。

Lombardo在一份聲明中表示：「迄今為止，我們對axolisimogene filolisbac的安全性和有效性十分有信心，因為我們在HPV相關癌症多項試驗中有超過250名患者，超過700次劑量。」

比如，2018年2月份時，Advaxis剛申請歐洲監管機構批准，將axalimogene filolisbac用於二線治療複發性或轉移性宮頸癌。這標誌著其Lm技術的首次上市應用。

FDA中止了試驗中的登記註冊和進一步給葯。Advaxis公司及其合作夥伴正與FDA合力解決此次臨床問題。Advaxis指出，目前其登記註冊和劑量在其他公司的臨床項目均未受影響。

Imfinzi並不是與axalimogene filolisbac配對的唯一PD-1抑製劑。該公司還將其領先產品與Merck公司的 Keytruda聯用治療前列腺癌，與Bristol-Myers Squibb公司的Opdivo聯用治療子宮頸複發性、轉移性鱗狀或非鱗狀細胞癌。

翻譯：鄭雲莉

原文

FDA Halts Advaxis Study Following Patient Death

Shares of Advaxis, Inc. are down more than 21 percent in premarket trading this morning after the company announced late Monday that the U.S. Food and Drug Administration halted a Phase I/II trial that uses an AstraZeneca Pharmaceuticals LP drug following the death of a patient.

The FDA placed a clinical hold on the combination study of axalimogene filolisbac and AstraZeneca』s Imfinzi (durvalumab). The combination therapy was being tested in the treatment of patients with advanced, recurrent or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer. The regulatory agency halted the trial on March 9 after the death from respiratory failure was reported at the end of February. The patient』s death followed the sixth combination cycle in the trial, the company said.

Advaxis』 axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based investigational immunotherapy. The drug uses live attenuated Listeria monocytogenes (Lm) bioengineered to produce and deliver tumor antigen/adjuvant fusion proteins within antigen presenting cells with the goal of generating strong, T-cell-mediated immunity. It is being combined with AstraZeneca』s approved PD-1 inhibitor Imfinzi. The AstraZeneca drug has been approved by the FDA for non-small cell lung cancer patients who cannot have their tumors surgically removed, as well as some bladder cancers.

Anthony Lombardo, the interim chief executive officer at Advaxis, said the company cares deeply for the patients involved in its trials and is concerned for their safety as it works to develop new treatment options for advanced cancers. To reassure investors and the industry He added that the company believes in the potential of its Lm Technology to develop those treatment options.

「We are confident in the safety and efficacy profile of axalimogene filolisbac, to date, based on our experience in over 250 patients and over 700 doses across multiple trials in HPV-associated cancers,」 Lombardo said in a statement.

Case in point, in February Advaxis is seeking regulatory approval in Europe for axalimogene filolisbac as a second-line treatment of recurrent or metastatic carcinoma of the cervix. This marked the first marketing application for its Lm Technology.

The FDA halted enrollment and further dosing in the trial. Advaxis and its partner are working with the FDA to resolve the clinical hold. Advaxis noted that enrollment and dosing in all other company clinical programs are unaffected at this time.

AstraZeneca』s Imfinzi isn』t the only PD-1 inhibitor that Advaxis is pairing axalimogene filolisbac with. The company has also combined its lead product with Merck』s Keytruda for the treatment of prostate cancer and Bristol-Myers Squibb』s Opdivo for recurrent or metastatic squamous or non-squamous cell carcinoma of the cervix.

來源：BioSpace

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