FGFR fusion

P3, N=641, Recruiting, Janssen Research & Development, LLC | Trial completion date: Jun 2028 --> Dec 2032

Our findings establish FGFR2::SHTN1 as a potent oncogenic driver in various cancers, particularly in cholangiocarcinoma, highlighting a unique mechanism of constitutive activation mediated by Shootin1's CCD-II domain. This study represents the first molecular characterization of the FGFR2::SHTN1 fusion, advances understanding of FGFR2 fusion biology, and identifies a particular target for future diagnostic and therapeutic strategies in relevant malignancies.

Loss of PRR14L prolongs SAC-dependent mitotic arrest in response to microtubule depolymerization but, paradoxically, leads to catastrophic mitotic errors upon SAC abrogation by MPS1 inhibitors. A model derived from our findings provides a rationale for exploiting MPS1 inhibition as a potential vulnerability in cancers containing either PRR14L loss of function mutations or FGFR-TACC3 fusions.

Safety was consistent with the overall FIGHT-207 population. Pemigatinib had antitumor activity and a manageable safety profile in patients with CNS tumors.

Our findings offer critical novel insights into functional FGFR fusions and bear considerable clinical implications for identifying individuals whose tumors are most likely to respond favorably to FGFR-targeted therapies.

While FGFR alterations are rare in glioma, patients with FGFR-altered GBM may have prolonged survival, which has implications for clinical trial design. We found loss of FGFR alteration at the time of subsequent surgery, raising concern for the therapeutic potential of FGFR-targeting agents in recurrent gliomas.

P2, N=83, Terminated, Incyte Corporation | Completed --> Terminated; Recruitment ceased after a pre-planned futility interim analysis indicated a low probability to confer a clinically meaningful improvement in objective response when compared to currently available therapies. There were no safety related concerns.

P2, N=316, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2025 --> Oct 2026

The primary endpoint (ORR) met the study's predefined success criteria. Tasurgratinib had a manageable safety profile consistent with previous reports and the known pharmacological profile of FGFR inhibitors.

This case highlights the efficacy of pemigatinib-based systemic therapy in achieving tumor regression and enabling curative resection in locally recurrent FGFR-2-positive ICC. The successful outcome underscores the potential of targeted therapies in managing recurrent ICC, warranting further investigation.

Despite major progress in biotechnology, our understanding on the role of fusion events in glioblastoma represented by the FGFR-TACC is still in its infancy. Here, we highlight recent progress on FGFR-TACC fusion in human glioblastoma, emphasizing their molecular mechanisms and potential clinical value.

To our knowledge, this is the first reported case of a PLPP5-FGFR1 fusion coexisting with a TP53 mutation in LUSC. These findings broaden the spectrum of potential translocation partners in FGFR1 fusions, and the clinical implications of this novel fusion on treatment outcomes and prognosis warrant further investigation and long-term follow-up.