XL820The clinical trial for this drug was halted in the fall of 2008. The information below is archival.
XL820, being developed by Exelixis, is an oral small molecule designed to block cancer growth signals and tumor angiogenesis (blood vessel formation). XL820 simultaneously blocks multiple protein kinase targets validated in a variety of cancers: wild type and mutant forms of KIT (including a KIT mutation associated with imatinib-resistance), VEGFR2/KDR, and PDGFR beta. In laboratory conditions, XL820 is able to block some of the secondary acquired mutations in KIT that make GIST resistant to both Gleevec and Sutent, particularly mutations in exon 17 of KIT.
As of September 2006, 23 patients had enrolled in a phase I dose-escalation study of XL820 testing an intermittent schedule with 5 daily doses given every 2 weeks. The study’s primary ends were to determine the maximum tolerable dose (MTD) and to assess the safety and tolerability of XL820. Four patients experienced stable disease for 3.5+ to 11+ months (one each with gastrointestinal stromal tumor [GIST = 3.5 months], renal cell carcinoma, testicular cancer and thyroid cancer). One instance of dose-limiting toxicity (grade 3) occurred. The MTD had not yet been determined at an oral dose up to 16 mg/kg for the intermittent dosing schedule.
Preliminary data from this study were reported at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in November 2006. You can access this information at the manufacturer's site as a pdf of the poster presented at the meeting. (Use the magnification feature to enlarge it to read it easily.) If you do not already have the free Adobe reader software to read the pdf, you can download it for free.
More mature data were presented in November 2007 at EORTC and can be accessed as a pdf of the poster at this link. These data indicate that the drug should be effective against some secondary mutations (such as some in exon 17 of KIT) that cause resistance to Gleevec and Sutent.
Exelixis was also evaluating a daily dosing regimen of XL820 in a separate Phase I study. Information about this is available at clinicaltrials.gov.
A new Phase II trial began in December 2007 as described at clinicaltrials.gov titled "A Phase 2 Study of XL820 in Adults With Advanced GIST Resistant to Imatinib and/or Sunitinib."