Quizartinib in Solid Tumors

Role of the KIT Kinase in Solid Tumors
Similar to FLT3 mutations in AML, mutations in KIT can lead to certain cancers including gastrointestinal stromal tumors (GIST) and melanoma. Several drugs targeting KIT have been approved as monotherapies to treat GIST, including Novartis' Gleevec^® and Pfizer's Sutent^®.

Quizartinib Development in Solid Tumors
Quizartinib may have utility in indications in which inhibition of KIT is known or suspected to yield a therapeutic benefit, such as GIST and KIT-mutant positive melanoma. Existing KIT inhibitors are generally effective in GIST patients, although the duration of response is limited as patients develop resistance. As a result, there is an unmet need for new treatments for relapsed and non-responding GIST patients. Ambit initiated a Phase 1 clinical trial of quizartinib in advanced solid tumors with a study design that uses a standard 3+3 dose escalation scheme with 50% dose increments. Once a maximum tolerated dose (MTD) has been determined, the trial will focus on patients with tumors in which KIT mutations are commonly found, particularly GIST.