Reference Detail

Ref Type Journal Article
PMID (28972963)
Authors Papadopoulos KP, El-Rayes BF, Tolcher AW, Patnaik A, Rasco DW, Harvey RD, LoRusso PM, Sachdev JC, Abbadessa G, Savage RE, Hall T, Schwartz B, Wang Y, Kazakin J, Shaib WL
Title A Phase 1 study of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid tumours.
Journal British journal of cancer
Vol 117
Issue 11
Date 2017 Nov 21
URL
Abstract Text ARQ 087 is an orally administered pan-FGFR inhibitor with multi-kinase activity. This Phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of ARQ 087 and defined the recommended Phase 2 dose (RP2D).Patients with advanced solid tumours received ARQ 087 administered initially at 25 mg every other day and dose-escalated from 25 to 425 mg daily (QD) continuous dosing. FGF19, 21, 23, and serum phosphate were assessed as potential biomarkers of target engagement.80 patients were enrolled, 61 in dose-escalation/food-effect cohorts and 19 with pre-defined tumour types in the expansion cohort. The most common ARQ 087-related adverse events were fatigue (49%), nausea (46%), aspartate aminotransferase (AST) increase (30%), and diarrhoea (23%). Four patients (5%) experienced grade 1 treatment-related hyperphosphataemia. Dose-limiting toxicity was reversible grade 3 AST increase. The RP2D was 300 mg QD. Pharmacokinetics were linear and dose-proportional from 25 to 325 mg QD, and were unaffected by food. Statistically significant changes (P-value<0.05) suggest phosphate and FGF19 levels as markers of target engagement. In 18 evaluable patients with FGFR genetic alterations, 3 confirmed partial responses (two intrahepatic cholangiocarcinomas (iCCA) with FGFR2 fusions and one urothelial cancer with FGFR2 and FGF19 amplification) and two durable stable disease at ⩾16 weeks with tumour reduction (FGFR2 fusion-positive iCCA and adrenocortical carcinoma with FGFR1 amplification) were observed.ARQ 087 had manageable toxicity at the RP2D of 300 mg QD, showed pharmacodynamics effects, and achieved objective responses, notably in patients with FGFR2 genetic alterations.

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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
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
SRC amp non-small cell lung carcinoma sensitive Derazantinib Phase I Actionable In a Phase I trial, ARQ 087 treatment resulted in 25% tumor reduction and stable disease for 36 weeks in a squamous non-small cell lung carcinoma patient harboring SRC amplification (PMID: 28972963; NCT01752920). 28972963 detail...
FGFR1 amp adrenocortical carcinoma sensitive Derazantinib Phase I Actionable In a Phase I trial, ARQ 087 treatment resulted in stable disease with a tumor reduction of 20% in an adrenocortical carcinoma patient harboring FGFR1 amplification, who remained on study for 3.5 years (PMID: 28972963; NCT01752920). 28972963
FGFR2 fusion intrahepatic cholangiocarcinoma sensitive Derazantinib Phase I Actionable In a Phase I trial, Derazantinib (ARQ 087) treatment resulted in partial response in 2 and stable disease in 1 of the 5 intrahepatic cholangiocarcinoma patients harboring FGFR2 fusions, and progressive disease in 5 patients without FGFR aberrations (PMID: 28972963; NCT01752920). detail... 28972963
Unknown unknown Advanced Solid Tumor not applicable Derazantinib Phase I Actionable In a Phase I trial, Derazantinib (ARQ 087) treatment resulted in partial response in 4.5% (3/67) and stable disease in 38.8% (26/67) of patients with advanced solid tumors (PMID: 28972963; NCT01752920). 28972963