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Ref Type Abstract
PMID
Authors M. Borad M. Javle W.L. Shaib K. Mody F. Bergamo W.P. Harris N. Damjanov T. Macarulla G. Brandi G. Masi M. Droz Dit Busset A. Boncompagni M. Dimova-Dobreva M. Engelhardt M. Saulay T.R. Halfdanarson J. Knox G.K. Abou-Alfa N. Personeni V. Mazzaferro
Title Efficacy of derazantinib in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions, mutations or amplifications
Journal Vol Issue Date Pages Journal Short Title
Annals of Oncology 33 Supplement 7 Sep 1, 2022
URL https://www.annalsofoncology.org/article/S0923-7534(22)01938-X/fulltext
Abstract Text Background In patients (pts) with iCCA, FGFR2 fusions (FGFR2F) occur in ∼15%, FGFR2 mutations or amplifications (FGFR2MA) in ∼5%. These pts have limited options after progression after 1L chemotherapy. Pemigatinib and Infigratinib have received accelerated FDA approval for chemorefractory CCA with FGFR2F. Derazantinib is a potent FGFR1-3 kinase inhibitor. Here, we present data from 143 patients with FGFR2F or FGFR2MA from the phase II study FIDES-01 (NCT03230318). Methods Eligible pts with advanced iCCA, ≥1 prior chemotherapy and FGFR2F or FGFR2MA received derazantinib 300 mg QD. FGFR2F were confirmed by FISH, FGFR2MA were identified by NGS. Primary endpoint was objective response rate (ORR) by central radiology review per RECIST v1.1 for pts with FGFR2F and progression-free survival (PFS) for pts with FGFR2MA. Response and safety was assessed in 103 pts with FGFR2F (ITT). In pts with FGFR2MA, safety was assessed in 40 pts (ITT) and response in 31 pts that were evaluable. Results 143 pts were dosed, median age 59 y, 63% female, 52% had ≥2 prior treatment lines. At data cutoff (25-Mar-2022), 98% of 103 pts with FGFR2F and 78% of 40 pts with FGFR2MA had discontinued treatment. In pts with FGFR2F, confirmed ORR was 21.4% (95% CI 13.9, 30.5), DCR 75.7% (95% CI 66.3, 83.6), mPFS 8.0 mo (95% CI 5.5, 8.3) and mOS 17.2 mo (95% CI 12.5, 22.4). In pts with FGFR2MA, confirmed ORR was 6.5% (95% CI 0.8, 21.4), DCR 58.1% (95% CI 39.1, 75.5), mPFS 8.3 mo (95% CI 1.9, 16.7) and mOS 15.9 mo (95% CI 8.4, NE). Most common adverse drug reactions (any grade / ≥G3) were hyperphosphatemia (37% / 3%), asthenia/fatigue (34% / 5%), nausea (30% / 1%), transaminase elevations (29% / 12%), dry mouth (27% / 0%) and dry eye (23% / 0%). Drug-related nail toxicities (8% / 0%), retinal events (1% / 0%), stomatitis (1% / 0%) and palmar-plantar erythrodysesthesia (PPE) (1% / 0%) were rare. Conclusions Derazantinib results in meaningful clinical benefit for pts with FGFR2 genetic aberrations including FGFR2F and FGFR2MA. Derazantinib-related toxicities were limited: PPE, stomatitis, retinal or nail toxicity were infrequent in the study population.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 fusion intrahepatic cholangiocarcinoma sensitive Derazantinib Phase II Actionable In a Phase II trial (FIDES-01), Derazantinib (ARQ 087) treatment resulted in an objective response rate of 21.4%, a disease control rate of 75.7%, median progression-free survival of 8.0 months, and a median overall survival of 17.2 months in patients with intrahepatic cholangiocarcinoma harboring an FGFR2 fusion (Ann Oncol (2022) 33 (suppl_7): S19-S26; NCT03230318). detail...
FGFR2 amp intrahepatic cholangiocarcinoma predicted - sensitive Derazantinib Phase II Actionable In a Phase II trial (FIDES-01), Derazantinib (ARQ 087) treatment resulted in an objective response rate of 6.5%, a disease control rate of 58.1%, median progression-free survival of 8.3 months, and a median overall survival of 15.9 months in patients with intrahepatic cholangiocarcinoma harboring an FGFR2 mutation or amplification (Ann Oncol (2022) 33 (suppl_7): S19-S26; NCT03230318). detail...
FGFR2 mutant intrahepatic cholangiocarcinoma predicted - sensitive Derazantinib Phase II Actionable In a Phase II trial (FIDES-01), Derazantinib (ARQ 087) treatment resulted in an objective response rate of 6.5%, a disease control rate of 58.1%, median progression-free survival of 8.3 months, and a median overall survival of 15.9 months in patients with intrahepatic cholangiocarcinoma harboring an FGFR2 mutation or amplification (Ann Oncol (2022) 33 (suppl_7): S19-S26; NCT03230318). detail...