Next Steps for Pemigatinib on FGFR Inhibition With Multiple Tumors, FDA Approval

Vivek Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, shares updates on pemigatinib in the upcoming FIGHT-302 study and highlights how an FDA approval will benefit patients with cholangiocarcinoma (CCA) harboring an FGFR2 mutation.

Transcript
Hello! I'm Dr. Vivek Subbiah from the University of Texas MD Anderson Cancer Center, Houston, Texas.

From this FIGHT-101 study, we understand that FGFR is an actionable alteration in cholangiocarcinoma (CCA) and beyond CCA in multiple tumor types. This been active in CCA, bladder cancer, brain tumors like pilocytic astrocytoma, head and neck cancer, pancreatic cancer, and non-small cell lung cancer.

The results of this study supported the design of the FIGHT-202 study. In fact, the FIGHT-202 study led to pemigatinib approval for advanced FGFR fusion-positive CCA. An important aspect of the FGFR FIGHT-101 study is that they also suggest potential benefit of pemigatinib in multiple other cancers with FGFR rearrangements and/or mutations. So this is one of the important findings of the study beyond the dose finding and beyond the pharmacokinetics and pharmacodynamics (PK/PD), and beyond the dose that led to a phase 2 study, that eventually led to an FDA approval.

Pemigatinib, now we know it's a potent and selective oral inhibitor, a pan-FGFR inhibitor of FGFR 1-3, and has shown anti-tumor activity and genetically defined models in patients now. Pemigatinib is now approved in Canada, Europe, Japan, and the USA. for treatment of adults with previously treated unresectable or metastatic advanced CCA that harbor the FGFR2 fusions. The approvals were based on efficacy and safety from the registration of phase 2 FIGHT-202 study in patients with CCA.

The FIGHT-101 study characterizes the PK and the PD of pemigatinib once daily monotherapy in patients with multiple solid tumors and established the dose. So, phase 2 studies of pemigatinib, as a next step as monotherapy, are ongoing in multiple tumor types, including a study of patients with myeloid lymphoid neoplasms with FGFR1 rearrangements, and that's called the FIGHT-203 study.

In addition, a randomized phase 3 study, called the FIGHT-302 study, is underway to evaluate the safety of pemigatinib versus standard therapy with gemcitabine plus cisplatin as first-line therapy in patients with advanced CCA harboring FGFR2 rearrangements.

Now, we know FGFR is an actionable target and the key is how do we get the FGFR drugs to the right patient, to the right clinic, at the right time? As we know, this FGFR inhibitor, pemigatinib, is associated with a manageable safety profile and the benefit versus the risk showed that the PD and the clinical activity, together with the responses, have been seen across multiple tumors driven by FGFR fusions and mutations.

These results have really prompted a registration study in CCA and that received FDA approval, that means any patient with CCA harboring an FGFR2 fusion in the unresectable, relapsed, refractory setting has a drug for access. And beyond this, there are several studies going on in multiple tumor types with this agent, and hopefully patients may benefit from FGFR inhibitors that may confer the gift of time to these patients. Thank you so much.