A phase Ib trial of FOLFIRINOX plus saridegib, an oral hedgehog (Hh) inhibitor, in pts with advanced pancreatic cancer (PDAC).

• DOI: 10.1200/jco.2012.30.15_suppl.3105
• Publication Date: 2020-03-11T15:10:19Z
• Authors: Andrew H. Ko; Noelle K. LoConte; Emily Kantoff; Robert W. Ross; Elizabeth G. Trehu; Margaret A. Tempero; Robin Katie Kelley; Alan Paul Venook; Timothy Wu; Hedy Lee Kindler
• Keywords: FOLFIRINOX; Mucositis

3105 Background: FOLFIRINOX has emerged as the optimal 1 st -line treatment option for pts with advanced PDAC and good performance status; whether it can serve backbone upon which to add targeted agents in clinical trial design remains uncertain. The goal of this multicenter phase Ib study is evaluate combination saridegib, a novel oral agent that inhibits Hh signaling pathway. In preclinical models PDAC, saridegib increases chemotherapy delivery by depleting peritumoral stroma increasing vascularity. Methods: Pts previously untreated metastatic or locally ECOG PS 0-1 were eligible. Treatment consists once-daily concurrent administration biweekly (omitting 5-FU bolus). A 3+3 dose escalation was used (see levels below). Prophylactic WBC growth factor support mandated. DLT definitions include ALT/AST ≥10x ULN, grade 4 plts ANC ≥5 d, 3-4 nonheme toxicity. CT scans are obtained every cycles. Limited PK analyses performed. Results: Seven have been enrolled at first 2 levels. Grade 1-2 AEs GI (N/V/D), dehydration, fatigue, LFT abnormalities. There one (grade 3 ALT elevation) DL2. Other serious toxicities seen nausea (DL1) diarrhea (DL2). Tumor shrinkage observed all DL1, ranging from 17-54%, unconfirmed PRs. Final MTD determination updated safety efficacy data will be presented meeting. Conclusions: modified regimen safely administered trials PDAC. While not beneficial when added gemcitabine separate randomized II study, early evidence significant responses on current suggests more intensive platform may represent preferable strategy design. [Table: see text]