新药介绍: 第三代EGFR TKI，EGF816-诺华和ASP8273-Astellas

值得期待的新药，感觉癌症最终变成类似高血压这样的慢性病已经不远了……

希望天天能有新药出来，造福！

期待

想知道，这药是不是和9291是一种类型的药？另外能告知一下购买途径和价格吗？谢谢

期待中......

Astellas在7月10日举行的R&D Meeting 2014上面公布了ASP8273的临床前数据



drugdiscovery_en.pdf (1.72 MB, 下载次数: 65)

2014-7-14 13:08 上传

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Exclusion Criteria：
Expansion cohorts only - subject has had prior treatment with an EGFR-T790M inhibitor (CO-1686, AZD9291)

——有点不理解，这句是指临床不接受之前接受过EGFR-T790M inhibitor的意思吗？那和1686 9291的区别在？

阿Q 发表于 2014-7-16 20:14
Exclusion Criteria：
Expansion cohorts only - subject has had prior treatment with an EGFR-T790M in ...

阿Q，你看前面写的是Expansion cohorts only，这个Phase I是分成两个部分的，其中第一个部分又分为两个队列，一个是剂量递增队列，是为了确定MTD和DLT，满足试验的主要终点，而扩展队列的作用是得到早期的有效率数据，也就是次要终点里面的DCR和PFS，这个队列里面的患者当然要排除同为T790M抑制剂的9291和1686的干扰，毕竟目前8273面向的是对第一代和第二代EGFR-TKI耐药的患者

东南偏东2013 发表于 2014-5-2 21:03
是么？能告知一下购买途径和价格吗？谢谢

YL出来了？

Early results for ASP8273 show response in treatment-resistant non-small cell lung cancer
http://www.ecco-org.eu/Global/Ne ... of-new-drug-ASP8273
In a second presentation looking at new ways of treating non-small cell lung cancer (NSCLC) that has both the EGFR and T790M mutations, researchers told the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics that an oral drug called ASP8273 has caused tumour shrinkage in patients in a phase I clinical trial in Japan.

Mutations of the epidermal growth factor (EGFR) occur in about 30-35% of Asian patients with NSCLC (and in 10-15% of Caucasian patients).

EGFR inhibitors called tyrosine kinase inhibitors (TKI), such as erlotinib, gefitinib and afatinib, can be used to treat EGFR-mutated NSCLC.

However, these patients will eventually develop resistance to EGFR TKI therapy, rendering their disease resistant to current treatments.

A further mutation called T790M accounts for 60% of this acquired resistance.

ASP8273 is a new drug that inhibits the EGFR mutation and the T790M resistance mutation.

Earlier research in mice had shown that it caused NSCLC to disappear completely, and so a phase I clinical trial was started in January 2014 to assess the drug’s safety and efficacy in humans.

Twenty-four Japanese patients have enrolled so far to receive one of six levels of doses (25, 50, 100, 200, 400 and 600mg) once a day.

A further seven patients have been enrolled into a second group to evaluate doses of 100mg, 200mg and 400mg a day (a dose escalation study), and the researchers are planning to enrol a total of 124 patients.

Cancer had progressed in all the patients after prior treatment with EGFR TKI therapy, and most of them had the T790M mutation.

Dr Haruyasu Murakami, of the Shizuoka Cancer Center, Shizuoka, Japan, told the meeting: “Preliminary results from this study show a high overall response rate of 78%, with tumours shrinking in seven out of nine patients who had both the EGFR and T790M mutations. While the number of patients is still small, this response is comparable with two other drugs in development that target EGFR – CO-1689 and AZ-9291 – but ASP8273 has fewer safety concerns than these drugs.”

The most common adverse reactions to ASP8273 were mild cases of diarrhoea (in half of the patients), nausea and vomiting (in a third of the patients).

There were none of the severe respiratory complications, heart problems and high blood sugar levels that have occurred during the clinical trials of the other two drugs.

One patient receiving 400mg a day suffered diarrhoea that was severe enough for the dose to be reduced.

The four patients who received 600mg a day had dose-limiting toxicities including severe diarrhoea, colitis (inflammation of the colon) and cholangitis (infection of the bile duct).

All the patients in the trial who had the T790M mutation remain in the trial without further progression of their disease.

“These data indicate that ASP8273 would be expected to have potential clinical benefits with fewer adverse side-effects compared to CO-1689 and AZ-9291,” Dr Murakami said.

The researchers are continuing to recruit patients to the phase I dose escalation study.

“We expect a recommended dose for a phase II trial to be determined soon and then we will start recruiting patients with both EGFR and T790M mutations immediately in Japan and other Asian countries. At present we are observing partial responses in patients receiving the 100mg dose and they are tolerating it well,” he concluded.

Prof Jean-Charles Soria, chair of the scientific committee for the EORTC-NCI-AACR Symposium and chair of the Drug Development Department at Gustave Roussy Cancer campus, France, commented “ASP8273 is the fourth EGFR-mutant specific kinase inhibitor in development for NSCLC patients with acquired resistance to EGFR inhibition related to appearance of the T790M mutation. Activity is clearly promising and toxicity is in line with the anticipated mechanism of action, but numbers are small and follow-up is quite immature at present.”