Phase I Trial Of The Hedgehog (Hh) Inhibitor, Lde225, In Combination With Etoposide And Cisplatin (Ep) For Initial Treatment Of Extensive Stage Small Cell Lung Cancer (Es-Sclc)

7602 Background: SCLC relies on the Hh developmental pathway for tumor initiation and progression. Pharmacologic blockade with Hh inhibitors blocks these processes. We performed a phase I study to determine the maximum tolerated dose (MTD) of LDE225, a selective, oral smoothened antagonist, in combination with EP in newly diagnosed ES-SCLC patients. Methods: Untreated patients with measurable disease, Karnofsky performance status ≥70, and asymptomatic brain metastases were eligible. All patients received 4 to 6 21-day cycles of EP (E, 120mg/m2 D1-3; P, 60mg/m2 D1) with daily LDE225. Patients with response or stable disease were continued on LDE225 until disease progression or unacceptable toxicity. Prophylactic cranial irradiation was performed after EP + LDE225, and LDE225 was held during that therapy. Two dose levels of LDE225 were planned: 400mg and 800mg daily, with 200mg daily de-escalation if necessary. Circulating tumor cells were quantified by Veridex Cell Search Platform at baseline and with dise...