Changes to fibroblast growth factor receptor (FGFR) genes are known to drive oncogenes and therefore represent attractive targets in various cancer types
A molecule being developed by Incyte, pemigatinib, acts on the 1, 2 and 3 subtypes and is undergoing clinical evaluation as a potential treatment for various forms of cancer, both as a monotherapy and in combination with immunotherapy.1
In an open label, multicentre Phase II study, 146 patients with cholangiocarcinoma, whose disease had progressed after at least one prior treatment, were enrolled into one of three cohorts depending on whether they had FGFR2 fusions/rearrangements, other FSF/FGFR alterations or none.2
All were given a starting dose of 13.5 mg once a day on a two weeks on/one week off schedule and could continue until their disease progressed or unacceptable toxicity occurred.
Of those with FGFR2 fusions or rearrangements, 38 (35.5%) achieved an objective response, with three complete and 35 partial responses. Hyperphosphataemia was the most common adverse event. In all, 71 patients died during the study, mostly because of disease progression; none were considered to be treatment related.
It is also being evaluated in combination with pembrolizumab, the programmed cell death protein 1 inhibitor.3
Subjects with refractory advanced malignancies that had progressed after previous therapy and for whom pembrolizumab treatment was relevant were given either pemigatinib as a monotherapy or in combination with the antibody.
Tumours included non-small cell lung cancer, sarcoma and bladder, pancreatic and testicular cancers.
After the initial dose-finding part of the study, subjects with FGF/FGFR alterations were included in a dose expansion stage. Patients received 9 or 13.5 mg daily doses of pemigatinib orally on a two weeks on/one week off regimen, plus 20 mg of intravenous pembrolizumab on the first day of the cycle.
No dose-limiting toxicities were observed and the higher dose was recommended. At the data cut-off point, 23 patients had been given the combination and 22 had discontinued therapy, primarily because of disease progression.
Five patients had a partial response, three of whom had FGFR mutations or rearrangements, and a further five achieved stable disease. Trials continue.