Reference Detail

Ref Type Journal Article
PMID (27870574)
Authors Nogova L, Sequist LV, Perez Garcia JM, Andre F, Delord JP, Hidalgo M, Schellens JH, Cassier PA, Camidge DR, Schuler M, Vaishampayan U, Burris H, Tian GG, Campone M, Wainberg ZA, Lim WT, LoRusso P, Shapiro GI, Parker K, Chen X, Choudhury S, Ringeisen F, Graus-Porta D, Porter D, Isaacs R, Buettner R, Wolf J
Title Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study.
Journal Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol 35
Issue 2
Date 2017 Jan 10
URL
Abstract Text Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1-amplified squamous cell non-small-cell lung cancer (sqNSCLC; arm 1) or other solid tumors with FGFR genetic alterations (mutations/amplifications/fusions) received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week-off schedule (arm 3). Results Data in 132 patients from the escalation and expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was determined on the basis of dose-limiting toxicities in four patients (100 mg, grade 3 aminotransferase elevations [n = 1]; 125 mg, hyperphosphatemia [n = 1]; 150 mg, grade 1 corneal toxicity [n = 1] and grade 3 aminotransferase elevations [n = 1]). Common adverse events in patients treated at the MTD (n = 57) included hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1-week-off schedule (RP2D). However, adverse event-related dose adjustments/interruptions were less frequent with the 3-weeks-on/1-week-off (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial responses [six confirmed]) was demonstrated with BGJ398 doses ≥ 100 mg in patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer. Conclusion BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile and showed antitumor activity in several tumor types, including FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancers.

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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
FGFR2 amp breast cancer sensitive BGJ398 Phase I Actionable In a Phase I trial, a breast cancer patient harboring an FGFR2 amplification demonstrated stable disease when treated with BGJ398 (PMID: 27870574). 27870574
FGFR2 fusion cholangiocarcinoma sensitive BGJ398 Phase I Actionable In a Phase I trial, two patients with cholangiocarcinoma harboring FGFR2 fusions demonstrated a decreased tumor burden when treated with BGJ398 (PMID: 27870574). 27870574
FGFR1 amp breast cancer sensitive BGJ398 Phase I Actionable In a Phase I trial, 28% (9/32) of breast cancer patients harboring FGFR1 amplification demonstrated stable disease when treated with BGJ398 (PMID: 27870574). 27870574
FGFR2 mutant cholangiocarcinoma sensitive BGJ398 Phase I Actionable In a Phase I trial, a patient with cholangiocarcinoma harboring an FGFR2 mutation demonstrated a decreased tumor burden when treated with BGJ398 (PMID: 27870574). 27870574
FGFR3 mutant bladder urothelial carcinoma sensitive BGJ398 Phase I Actionable In a Phase I trial, patients with bladder urothelial carcinoma harboring an FGFR3 mutation demonstrated a disease control rate of 75% (6/8) when treated with BGJ398, including 3 patients with a partial response and 3 with stable disease (PMID: 27870574; NCT01004224). 27870574
FGFR1 amp lung squamous cell carcinoma sensitive BGJ398 Phase I Actionable In a Phase I trial, patients with lung squamous cell carcinoma harboring an FGFR1 amplification demonstrated a disease control rate of 50% (18/36) when treated with BGJ398, resulting in 14 patients with stable disease and 4 patients with a partial response (PMID: 27870574). 27870574