Related Experiment Video
Updated: Dec 16, 2025
![Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F68356.jpg&w=3840&q=50)
Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with
R Bahleda1, F Meric-Bernstam2, L Goyal3
1Early Drug Development Department (DITEP), Gustave Roussy Cancer Center, Villejuif, France.
Background:
Futibatinib is an oral, irreversible, highly selective fibroblast growth factor receptor (FGFR)1-4 inhibitor with potent preclinical activity against tumors harboring FGFR aberrations. This first-in-human, phase I dose-escalation trial (NCT02052778) evaluates the safety and pharmacokinetics/pharmacodynamics of futibatinib in advanced solid tumors.
Patients And Methods:
Following a standard 3+3 dose-escalation design, eligible patients with advanced solid tumors refractory to standard therapies received 8-200 mg futibatinib three times a week (t.i.w.) or 4-24 mg once daily (q.d.).
Results:
A total of 86 patients were enrolled in the nine t.i.w. (n = 42) and five q.d. cohorts (n = 44); 71 patients (83%) had tumors harboring FGF/FGFR aberrations. Three of nine patients in the 24-mg q.d. cohort experienced dose-limiting toxicities, including grade 3 increases in alanine transaminase, aspartate transaminase, and blood bilirubin (n = 1 each). The maximum tolerated dose (MTD) was determined to be 20 mg q.d.; no MTD was defined for the t.i.w. schedule. Across cohorts (n = 86), the most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (59%), diarrhea (37%), and constipation (34%); 48% experienced grade 3 TEAEs. TEAEs led to dose interruptions, dose reductions, and treatment discontinuations in 55%, 14%, and 3% of patients, respectively. Pharmacokinetics were dose proportional across all q.d. doses but not all t.i.w. doses evaluated, with saturation observed between 80 and 200 mg t.i.w. Serum phosphorus increased dose dependently with futibatinib on both schedules, but a stronger exposure-response relationship was observed with q.d. dosing, supporting 20 mg q.d. as the recommended phase II dose (RP2D). Overall, partial responses were observed in five patients [FGFR2 fusion-positive intrahepatic cholangiocarcinoma (n = 3) and FGFR1-mutant primary brain tumor (n = 2)], and stable disease in 41 (48%).
Conclusions:
Futibatinib treatment resulted in manageable safety, pharmacodynamic activity, and preliminary responses in patients with advanced solid tumors. The results of this phase I dose-escalation trial support 20 mg q.d. futibatinib as the RP2D.
Clinical Trial Registration:
FOENIX-101 (ClinicalTrials.gov, NCT02052778).
Insights
Futibatinib, an FGFR inhibitor, showed manageable safety and preliminary responses in advanced solid tumors. The recommended Phase II dose is 20 mg once daily, supporting further clinical trials.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Futibatinib is an oral, irreversible, selective FGFR inhibitor with preclinical efficacy.
- It targets tumors with FGFR aberrations.
Purpose of the Study:
- Evaluate safety and pharmacokinetics/pharmacodynamics of futibatinib.
- Determine the recommended Phase II dose (RP2D).
Main Methods:
- Phase I, open-label, dose-escalation trial (NCT02052778).
- 86 patients with advanced solid tumors received futibatinib (8-200 mg t.i.w. or 4-24 mg q.d.).
- Standard 3+3 dose-escalation design.
Main Results:
- Maximum tolerated dose (MTD) was 20 mg q.d.
- Common adverse events: hyperphosphatemia (59%), diarrhea (37%).
- Partial responses in 5 patients (cholangiocarcinoma, brain tumors); 48% had stable disease.
Conclusions:
- Futibatinib demonstrated manageable safety and pharmacodynamic activity.
- Preliminary antitumor responses observed in advanced solid tumors.
- 20 mg q.d. is the recommended Phase II dose.
![An Automated Radiosynthesis of [68Ga]Ga-FAPI-46 for Routine Clinical Use](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F66708.jpg&w=3840&q=50)
