Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (30745300)
Authors Voss MH, Hierro C, Heist RS, Cleary JM, Meric-Bernstam F, Tabernero J, Janku F, Gandhi L, Iafrate AJ, Borger DR, Ishii N, Hu Y, Kirpicheva Y, Nicolas-Metral V, Pokorska-Bocci A, Vaslin Chessex A, Zanna C, Flaherty KT, Baselga J
Title A Phase I, Open-Label, Multicenter, Dose-escalation Study of the Oral Selective FGFR Inhibitor Debio 1347 in Patients with Advanced Solid Tumors Harboring FGFR Gene Alterations.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 25
Issue 9
Date 2019 May 01
URL
Abstract Text To investigate tolerability, efficacy, and pharmacokinetics/pharmacodynamics of Debio 1347, a selective FGFR inhibitor.This was a first-in-human, multicenter, open-label study in patients with advanced solid tumors harboring FGFR1-3 gene alterations. Eligible patients received oral Debio 1347 at escalating doses once daily until disease progression or intolerable toxicity. Dose-limiting toxicities (DLT) were evaluated during the first 4 weeks on treatment, pharmacokinetics/pharmacodynamics postfirst dose and after 4 weeks.A total of 71 patients were screened and 58 treated with Debio 1347 at doses from 10 to 150 mg/day. Predominant tumor types were breast and biliary duct cancer, most common gene alterations were FGFR1 amplifications (40%) and mutations in FGFR2 (12%) and FGFR3 (17%); 12 patients (21%) showed FGFR fusions. Five patients at three dose levels had six DLTs (dry mouth/eyes, hyperamylasemia, hypercalcemia, hyperbilirubinemia, hyperphosphatemia, and stomatitis). The maximum tolerated dose was not reached, but dermatologic toxicity became sometimes dose limiting beyond the DLT period at ≥80 mg/day. Adverse events required dose modifications in 52% of patients, mostly due to dose-dependent, asymptomatic hyperphosphatemia (22%). RECIST responses were seen across tumor types and mechanisms of FGFR activation. Six patients, 3 with FGFR fusions, demonstrated partial responses, 10 additional patients' tumor size regressions of ≤30%. Plasma half-life was 11.5 hours. Serum phosphate increased with Debio 1347 plasma levels and confirmed target engagement at doses ≥60 mg/day.Preliminary efficacy was encouraging and tolerability acceptable up to 80 mg/day, which is now used in an extension part of the study.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

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
Debio 1347 CH5183284|FF284|debiopharm 1347 FGFR1 Inhibitor 23 FGFR2 Inhibitor 15 FGFR3 Inhibitor 13 Debio 1347 inhibits FGFR-1, -2, and -3, resulting in decreased downstream signaling, and potentially leading to reduced tumor cell proliferation and angiogenesis, and increased cell death in FGFR-overexpressing tumor cells (PMID: 30745300).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
FGFR2 DDX21 FGFR2 - DDX21 fusion unknown FGFR2-DDX21 results from the fusion of FGFR2 and DDX21 (PMID: 30745300). FGFR2-DDX21 has been identified in cholangiocarcinoma (PMID: 30745300, PMID: 28642281), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2020).
FGFR2 KIAA1217 FGFR2 - KIAA1217 fusion unknown FGFR2-KIAA1217 results from the fusion of FGFR2 and KIAA1217 (PMID: 30745300). FGFR2-KIAA1217 has been identified in cholangiocarcinoma (PMID: 30745300, PMID: 31109923), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2020).
FGFR2 ROCK1 FGFR2 - ROCK1 fusion unknown FGFR2-ROCK1 results from the fusion of FGFR2 and ROCK1 (PMID: 30745300). FGFR2-ROCK1 has been identified in cholangiocarcinoma (PMID: 30745300), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Feb 2020).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR3 mutant Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR3 - TACC3 transitional cell carcinoma predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in two patients with urothelial cancer harboring FGFR3-TACC3 (PMID: 30745300; NCT01948297). 30745300
FGFR3 amp Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR2 amp breast cancer sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in a stable disease with 19.4% reduction of tumor size and 41% decrease of DUSP6 score in a patient with lung squamous cell carcinoma harboring FGFR2 amplification (PMID: 30745300; NCT01948297). 30745300
FGFR2 amp uterine cancer predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in a stable disease with 3.9% change of tumor size and 60% decrease of DUSP6 score in a patient with uterine cancer harboring FGFR2 amplification (PMID: 30745300; NCT01948297). 30745300
FGFR2 amp FGFR2 mut cervical adenocarcinoma predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in a partial response with 50% reduction of tumor size and 56% decrease of DUSP6 score in a patient with cervical adenocarcinoma harboring FGFR2 amplification and FGFR2 mutation (PMID: 30745300; NCT01948297). 30745300
FGFR2 - INA colon cancer predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in a partial response in 2 patient with colon cancer harboring FGFR2-INA (PMID: 30745300; NCT01948297). 30745300
FGFR2 - KIAA1217 cholangiocarcinoma predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in stable disease in a patient with cholangiocarcinoma harboring FGFR2-KIAA1217 (PMID: 30745300; NCT01948297). 30745300
FGFR2 fusion FGFR1 amp colon cancer predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in a partial response with 49.5% reduction of tumor size and 66% decrease of DUSP6 score in a patient with colon cancer harboring FGFR1 amplification and FGFR2 fusion (PMID: 30745300; NCT01948297). 30745300
FGFR2 amp Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR2 fusion Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR1 amp Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR1 amp lung squamous cell carcinoma predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in a stable disease with 26.7% reduction of tumor size and 100% decrease of DUSP6 score in a patient with lung squamous cell carcinoma harboring FGFR1 amplification (PMID: 30745300; NCT01948297). 30745300
FGFR3 fusion Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR3 - TACC3 gallbladder cancer predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in stable disease in a patient with gallbladder cancer harboring FGFR3-TACC3 (PMID: 30745300; NCT01948297). 30745300
FGFR2 - DDX21 cholangiocarcinoma predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in stable disease in a patient with cholangiocarcinoma harboring FGFR2-DDX21 (PMID: 30745300; NCT01948297). 30745300
FGFR1 fusion Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR2 - ROCK1 cholangiocarcinoma predicted - sensitive Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, Debio 1347 treatment resulted in stable disease in a patient with cholangiocarcinoma harboring FGFR2-ROCK1 (PMID: 30745300; NCT01948297). 30745300
FGFR2 mutant Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR1 mutant Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300