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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
A phase I, first in human study of FP-1039 (GSK3052230), a novel FGF ligand trap, in patients with advanced solid
A W Tolcher1, K P Papadopoulos2, A Patnaik2
1South Texas Accelerated Research Therapeutics (START), San Antonio atolcher@start.stoh.com.
Background:
Fibroblast growth factors (FGFs) play important roles in multiple cancers by supporting tumor growth and angiogenesis. FP-1039 (GSK3052230) is a FGF ligand trap consisting of the extracellular domain of FGF receptor 1 (FGFR1) fused with the Fc region of IgG1. FP-1039 binds and neutralizes multiple FGFs that normally bind FGFR1. The primary objective of this phase I study was to evaluate the safety and tolerability of FP-1039.
Patients And Methods:
Eligible patients with metastatic or locally advanced solid tumors for which standard treatments were ineffective were treated with weekly doses of FP-1039 for 4 weeks, followed by 2 weeks observation.
Results:
Thirty-nine subjects received a mean of 6 infusions of FP-1039 at doses ranging from 0.5 to 16 mg/kg weekly, with no maximally tolerated dose identified. Grade 3 or greater treatment emergent adverse events were uncommon. Four dose-limiting toxicities were reported at doses of 0.75 mg/kg (urticaria), 1 mg/kg (intestinal perforation and neutropenia), and 16 mg/kg (muscular weakness). Drug exposure was dose proportional, and the terminal elimination half-life was 2.6-3.9 days following a single dose. Target engagement as measured by low free plasma FGF2 levels was achieved. FGF pathway dysregulation was uncommon. No objective responses were observed.
Conclusion:
In nonselected cancer patients with advanced disease, treatment with FP-1039 was well tolerated and toxicities associated with small molecule drugs that inhibit FGFR tyrosine kinases, including hyperphosphatemia, were not observed. Further studies of FP-1039 in patients selected for FGF pathway dysregulation, who are most likely to benefit, are now underway.
Insights
FP-1039, a novel FGF ligand trap, demonstrated good tolerability in patients with advanced cancers. Unlike FGFR inhibitors, it did not cause common toxicities, suggesting potential for selected patient populations.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Fibroblast growth factors (FGFs) are crucial for tumor growth and angiogenesis in various cancers.
- FP-1039 is a FGF ligand trap designed to neutralize FGFs that bind to FGF receptor 1 (FGFR1).
Purpose of the Study:
- To assess the safety and tolerability of FP-1039 in a Phase I clinical trial.
- To evaluate the pharmacokinetic profile and target engagement of FP-1039.
Main Methods:
- A Phase I study treated patients with advanced solid tumors unresponsive to standard therapies with weekly FP-1039.
- Dosing ranged from 0.5 to 16 mg/kg, followed by a 2-week observation period.
Main Results:
- FP-1039 was administered at doses up to 16 mg/kg without identifying a maximum tolerated dose.
- Grade 3+ adverse events were infrequent; dose-limiting toxicities included urticaria, intestinal perforation, neutropenia, and muscular weakness.
- Target engagement was confirmed by reduced plasma FGF2 levels, with minimal FGF pathway dysregulation observed.
Conclusions:
- FP-1039 was well-tolerated in patients with advanced cancer, lacking the typical toxicities of FGFR tyrosine kinase inhibitors.
- Future studies will focus on patients with specific FGF pathway dysregulation who may benefit most from FP-1039 therapy.
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