{"id":4382,"date":"2017-04-20T14:50:13","date_gmt":"2017-04-20T18:50:13","guid":{"rendered":"http:\/\/blogs.shu.edu\/cancer\/?p=4382"},"modified":"2021-07-02T08:51:42","modified_gmt":"2021-07-02T12:51:42","slug":"bad-news-for-anti-stem-cell-approaches","status":"publish","type":"post","link":"https:\/\/blogs.shu.edu\/cancer\/2017\/04\/20\/bad-news-for-anti-stem-cell-approaches\/","title":{"rendered":"Bad news for anti-stem cell approaches"},"content":{"rendered":"

OncoMed announced setbacks in the development of drugs<\/a> aimed at cancer stem cells:<\/p>\n

    \n
  1. Tarextumab, which targets Notch 2\/3 receptors, plus chemotherapy failed to slow progression-free survival in patients with small cell lung cancer compared to chemotherapy, alone. Biomarkers indicative of Notch pathway activation did not reveal activity of the treatment;<\/li>\n
  2. Brontictuzumab, which targets Notch 1, was not tolerable in combination with\u00a0Taiho Oncology’s Lonsurf (trifluridine\/tipiracil)\u00a0for the third-line treatment of patients with colorectal cancer;<\/li>\n
  3. Demcizumab, which targets DLL4 (an activator of Notch), failed a midstage trial in patients with treatment-naive pancreatic cancer;<\/li>\n
  4. Bayer decided not to license vantictumab (wich targets Frizzled membrane proteins that activate the Wnt pathway) and ipafricept (which binds Wnt ligands).<\/li>\n<\/ol>\n

    These compounds figured prominently in the OncoMed pipeline<\/a>. we have discussed them on this blog, previously, in the context of bone toxicity induced by vantictutmab<\/a>. So, the drug was exhibiting in vivo activity, albeit, off-target.<\/p>\n

    Regarding tarextumab:<\/p>\n

    The\u00a0PINNACLE trial\u00a0randomised 145\u00a0previously untreated\u00a0patients with\u00a0extensive-stage\u00a0SCLC to receive tarextumab in combination with etoposide plus carboplatin or cisplatin, or to receive chemotherapy\u00a0plus placebo.\u00a0<\/em><\/p>\n

    According to\u00a0OncoMed, results showed that median PFS in the tarextumab arm was 5.6 months, versus 5.5 months in the\u00a0placebo group.\u00a0Meanwhile, median OS was 9.3 months among tarextumab-treated patients, compared with 10.3 months for those who only received chemotherapy.\u00a0Additionally, overall response rates in the tarextumab and\u00a0placebo\u00a0groups were 68.5 percent and 70.8 percent, respectively.\u00a0OncoMed also noted\u00a0that five\u00a0individual Notch biomarkers had failed to identify a definitive subset of patients\u00a0with a treatment\u00a0effect on either PFS or OS.\u00a0<\/em><\/p>\n

    We wait to see whether targeting Notch and Wnt via other compounds and approaches can provide clinical benefit.<\/p>\n","protected":false},"excerpt":{"rendered":"

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