A first-in-human phase 1b study of a novel allosteric extracellular FGFR2 inhibitor alofanib in patients with refractory metastatic gastric cancer.

Tjulandin, Sergei; Statsenko, Galina; Артамонова, Е. В.; Vladimirova, Liubov Yu; Бесова, Н. С.; Mochalova, Anastasia; Рыков, И. В.; Moiseyenko, Vladimir; Utyashev, Igor; Iugai, Sergei; Kazey, V. I.; Dragun, Nadezhda; Reznikov, D.; Gavrilova, Evgenia; Tsimafeyeu, Ilya

doi:10.1200/jco.2022.40.4_suppl.304

Cited by 3 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aflofanib (RPT835) is a novel selective allosteric FGFR2 inhibitor, which has been evaluated in breast, ovarian, and gastric cancers [106,107]. In a phase Ib trial of previously treated patients (at least one prior line) with metastatic gastric adenocarcinoma, it showed acceptable tolerability and some clinical efficacy with an ORR rate of 9.5% and DCR of 71.4% [106].…”

Section: Selective Fgfr Inhibitorsmentioning

confidence: 99%

Molecular Targeting of the Fibroblast Growth Factor Receptor Pathway across Various Cancers

Shan,

Dalal,

Thaw Dar

et al. 2024

IJMS

View full text Add to dashboard Cite

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that are involved in the regulation of cell proliferation, survival, and development. FGFR alterations including amplifications, fusions, rearrangements, and mutations can result in the downstream activation of tyrosine kinases, leading to tumor development. Targeting these FGFR alterations has shown to be effective in treating cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid neoplasms, and there are currently four FGFR inhibitors approved by the Food and Drug Administration (FDA). There have been developments in multiple agents targeting the FGFR pathway, including selective FGFR inhibitors, ligand traps, monoclonal antibodies, and antibody–drug conjugates. However, most of these agents have variable and low responses, with some intolerable toxicities and acquired resistances. This review will summarize previous clinical experiences and current developments in agents targeting the FGFR pathway, and will also discuss future directions for FGFR-targeting agents.

show abstract

Section: Selective Fgfr Inhibitorsmentioning

confidence: 99%

Molecular Targeting of the Fibroblast Growth Factor Receptor Pathway across Various Cancers

Shan,

Dalal,

Thaw Dar

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Aflofanib (RPT835) is a novel selective allosteric FGFR2 inhibitor, which has been evaluated in breast, ovarian and gastric cancers [105,106]. In a phase Ib trial of previously treated patients (at least one prior line) with metastatic gastric adenocarcinoma, it showed acceptable tolerability and some clinical efficacy with ORR rate of 9.5% and DCR of 71.4% [105].…”

Section: Derazantinib (Arq-087mentioning

confidence: 99%

Molecular Targeting of the Fibroblast Growth Factor Receptor (FGFR) Pathway Across Various Cancers

Shan,

Dalal,

Thaw Dar

et al. 2023

Preprint

View full text Add to dashboard Cite

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that involve in regulation of cell proliferation, survival, and development. FGFR alterations including amplifications, fusions, rearrangements, and mutations can result downstream activation of tyrosine kinases leading to tumor development. Targeting those FGFR alterations has shown to be effective in cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid neoplasms and there are currently four FGFR inhibitors approved by the Food and Drug Administration (FDA). There have been developments of multiple agents targeting FGFR pathway including selective FGFR inhibitors, ligand traps, monoclonal antibodies, and antibody drug conjugates. However, most of these agents have variable and low responses with some intolerable toxicities and acquired resistances. This review will summarize previous clinical experiences and current developments of agents targeting FGFR pathway and discuss future directions of FGFR targeting agents.

show abstract

“…No dose limiting toxicities were reported and the recommended phase II dose was established. 60 Derazantinib has shown anti-tumour activity in GC murine models 61 and has been shown to inhibit CSF1R and downregulate immunosuppressive macrophage activity which may improve susceptibility to therapeutic immune checkpoint blockade with PD-L1 antibodies. 62,63 Derazantinib is currently being investigated in a phase Ib/II trial.…”

Section: Dovepressmentioning

confidence: 99%

Targeting FGFR2 Positive Gastroesophageal Cancer: Current and Clinical Developments

Gordon¹,

Johnston²,

Lau³

et al. 2022

OTT

View full text Add to dashboard Cite

Despite recent advances in the systemic treatment of gastroesophageal cancers, prognosis remains poor. Comprehensive molecular analyses have characterized the genomic landscape of gastroesophageal cancer that has established therapeutic targets such as human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor (VEGFR) and programmed death ligand 1 (PD-L1). The aberrant fibroblast growth factor receptor 2 (FGFR2) pathway is attractive for targetable therapy with FGFR inhibition based on preclinical data showing a pivotal role in the progression of gastric cancer (GC). FGFR2 amplification is the most common FGFR2 gene aberration in gastroesophageal cancer, and most associated with diffuse GC, which is often linked to poorer prognostic outcomes. There has been considerable progress with drug development focused on FGFR inhibition. At present, there is no approved FGFR inhibitor for FGFR2 positive gastroesophageal cancer. A selective FGFR2b monoclonal antibody bemarituzumab is currently being investigated in the first phase III randomized trial for patients with first line advanced GC, which may change the treatment paradigm for FGFR2b positive GC. The role of FGFR signalling, specifically FGFR2 , is less established in oesophageal squamous cell cancer (ESCC) with a paucity of evidence for clinical benefit in these patients. Precision medicine is part of the wider approach in gastrointestinal cancers; however, it can be challenging due to heterogeneity and here circulating tumour DNA (ctDNA) for patient selection may have future clinical utility. In our review, we outline the FGFR pathway and focus on the developments and challenges of targeting FGFR2 driven gastroesophageal cancers.

show abstract

A first-in-human phase 1b study of a novel allosteric extracellular FGFR2 inhibitor alofanib in patients with refractory metastatic gastric cancer.

Cited by 3 publications

References 0 publications

Molecular Targeting of the Fibroblast Growth Factor Receptor Pathway across Various Cancers

Molecular Targeting of the Fibroblast Growth Factor Receptor Pathway across Various Cancers

Molecular Targeting of the Fibroblast Growth Factor Receptor (FGFR) Pathway Across Various Cancers

Targeting FGFR2 Positive Gastroesophageal Cancer: Current and Clinical Developments

Contact Info

Product

Resources

About