CXCR4 antagonist exhibits anti-tumor efficacy in a population of patients who are not treated with Opdivo monotherapy
May 18, 2018 Source: Sina Pharmaceutical
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];X4 Pharma is a clinical-stage biotechnology company focused on developing new CXCR4 antagonists that promote the transport of immune cells to treat cancer and rare diseases. Recently, the company announced a pilot study of experimental drug X4P-001-IO combined with Bristol-Myers Squibb PD-1 tumor immunotherapy Opdivo (nivolumab). The study was conducted in Opdivo monotherapy-free clear cell renal cell carcinoma (ccRCC) patients, and data was presented at the 16th Annual Meeting of the Association for Cancer Immunotherapy (CIMT) in Mainz, Germany.
The data presented this time were from 9 patients with advanced ccRCC, all of whom were unresponsive or stable or progressing to Opdivo monotherapy. In the study, patients continued to receive standard 2-week treatment with 240 mg Opdivo and received X4P-001-IO (400 mg, orally, once daily) for a median duration of 3.7 months (1-10 months). The highlight data announced at the meeting included:
(1) The combination of X4P-001-IO and Opdivo has acceptable toxicity. The most common adverse reactions include diarrhea, nasal congestion, dry eye, headache, and cough. No grade 4 or 5 adverse events occurred, and all grade 3/serious adverse events can be managed with appropriate intervention.
(2) X4P-001-IO combined with Opdivo showed anti-tumor activity in some patients with advanced ccRCC: 4 patients who underwent treatment with Opdivo monotherapy had achieved optimal remission after treatment with combination therapy. Another 5 patients who received stable treatment with Opdivo monotherapy had partial remission after receiving combination therapy.
David F. McDermott, principal investigator of the study and professor at Harvard Medical School, said the data suggest that X4P-001-IO and Opdivo may be enhanced in patients receiving anti-PD-1 checkpoint inhibitor Opdivo monotherapy. Treatment is relieved, but these positive preliminary data need to be validated in larger clinical studies.
Sudha Parasuraman, chief medical officer of X4 Pharma, said the findings helped us to recognize more and more of the combination of CXCR4 antagonists with other drugs such as checkpoint inhibitors. Since CXCR4 antagonism and checkpoint inhibition work at different sites in the tumor's immune cycle, it is reasonable to consider the synergistic potential of the two.
The drugs in the X4 Pharma pipeline are oral small molecule drugs that antagonize the CXCR4 pathway, and the CXCR4 pathway is central to immune surveillance. The fastest-growing line in the company's pipeline is X4P-001-RD, which is currently in Phase II/III clinical trial of WHIM syndrome, a rare hereditary, primary immunodeficiency disease.
X4P-001-IO is X4P's most important oncology asset, a selective, oral, small molecule CXCR4 antagonist. CXCR4, CXC receptor type 4, is a chemokine receptor that is abundant in some immune cells and cancer cells, and plays a key role in the transport, invasion and activation of immune cells in the tumor microenvironment. . The CXCR4 signaling pathway is disrupted in a wide range of cancers, promoting tumor growth by allowing cancer cells to evade immune surveillance and produce a protumor microenvironment. X4P-001-IO can help restore immunity in the tumor microenvironment and has the potential to enhance the anti-tumor activity of marketed and emerging oncology drugs, such as immunological checkpoint inhibitors and targeted agents.
Currently, X4P-001-IO is being evaluated in a number of solid tumor clinical studies, including the combination of Mercker PD-1 tumor immunotherapy Keytruda (pembrolizumab) for melanoma; and the combination of Pfizer targeted anticancer agent Inlyta (axitinib) for advanced ccRCC. A previously published phase Ib clinical trial showed that X4P-001-IO combined with Inlyta increased disease control rate to 92%, higher than Inlyta monotherapy; especially in 1 of 14 patients achieved complete remission, which It has never been observed in Inlyta's large clinical studies.
In addition to the above two drugs, X4 has another new drug project, X4P-002, which crosses the blood-brain barrier and is currently developing a treatment for glioblastoma multiforme, a deadly brain. Tumor. (Sina Pharmaceutical Compilation/newborn)
Article, picture reference source: X4's IO combination pilot shows new activity compared to Opdivo alone
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