Pemazyre (pemigatinib)

The FGFR and IDH-1 pathways are the primary targets for therapy, with FGFR-2 and IDH-1 inhibitors, such as Pemigatinib and Ivosidenib respectively, already available on the market. This prospective study validates the prevalence of mutations documented in the literature and underscores the significance of NGS in presenting supplementary therapeutic avenues. Moreover, we demonstrated the role of other potential targets co-expressed with FGFR2 or IDH1 which could represent a crucial opportunity for novel combinations or sequences therapies.

Our results seem to confirm the negative prognostic role in terms of PFS of GA in BAP1 and CDKN2A genes in patients affected by locally advanced or metastatic FGFR2-positive CCA treated with pemigatinib in a real-world setting.

He underwent an uncomplicated LDLT (including an uncomplicated donor surgery) and at one year follow-up is without evidence of disease recurrence. We believe this is the first report of LDLT for this indication.

On this basis, the present review aims at providing an overview of recently explored connections between the FGF/FGFR system and c-Myc oncoprotein, sustaining the therapeutic potential of targeting the FGF/FGFR/c-Myc axis in MM by using inhibitors targeting FGF ligands or FGF receptors. Importantly, the provided findings may represent the rationale for using FDA approved FGFR TK inhibitors (i.e. Pemigatinib, Futibatinib, Erdafitinib) for the treatment of MM patients presenting with an aberrant activation of this axis.

P2, N=40, Not yet recruiting, UNICANCER

No abstract available

P2, N=27, Not yet recruiting, University of Utah | Trial completion date: Dec 2025 --> Dec 2030 | Initiation date: Apr 2024 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2026

No abstract available

The drug accessibility rate of ICC is high and pemigatinib is effective and well-tolerated in ICC patients harboring FGFR2 gene fusions.

P2, N=206, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=300 --> 206

P2, N=47, Active, not recruiting, Incyte Corporation | Trial completion date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jul 2024 --> Oct 2024

P2, N=30, Recruiting, Sun Yat-sen Memorial Hospital Sun Yat-sen University; Sun Yat-sen Memorial Hospital Sun Yat-sen University

P2, N=33, Recruiting, Lund University Hospital | Not yet recruiting --> Recruiting

At progression to FGFR inhibitors, FGFR2-driven malignancies are characterized by high intra- and inter-patient molecular heterogeneity, particularly in cholangiocarcinoma. Resistance to FGFR inhibitors can be overcome by sequential, molecularly-oriented treatment strategies across FGFR2-driven tumors.

This study complements the FIGHT-202 clinical trial by assessing the use of pemigatinib among a diverse population of patients with CCA under real-world conditions. Findings support the clinical benefit of pemigatinib demonstrated in FIGHT-202.

The most frequently assigned TTs were IPI/NIVO (37%), ipatasertib (16%), pemigatinib (8%), TDM1 (8%), and atezo/ipatasertib (6%). The ROME Trial demonstrated that a mutational-based treatment approach based on the MTB discussion of CGP results may significantly improve ORR and PFS compared to SoC in pretreated patients with metastatic solid tumors, particularly with immunotherapy.

P2, N=30, Not yet recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Twenty-seven studies finally met all inclusion criteria. The promising results emerging from Pemigatinib preclinical and clinical studies pave the way for Pemigatinib extension to multiple solid cancer settings.

P2, N=38, Not yet recruiting, Eastern Hepatobiliary Surgery Hospital

P3, N=167, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=434 --> 167

Conventional chemotherapy with gemcitabine and cisplatin for 19 months resulted in progressive disease. Subsequently, a comprehensive genome profile revealed fibroblast growth factor receptor 2 rearrangement, and hence, pemigatinib administration was initiated...Subsequently, the patient underwent conversion surgery, resulting in successful radical resection of the tumor. The patient has been disease-free for 7 months.

This case strengthens the current guidelines for continuing pemigatinib in asymptomatic patients found to have subretinal fluid. Further studies are warranted to identify patients who may be at higher risk for developing subretinal fluid.

In addition, USP8 depletion promoted the response of iCCA to pemigatinib. In conclusion, our findings pointed to a previously undocumented catalytic role for USP8 as a deubiquitinating enzyme of OGT. The USP8-OGT axis could be a potential target for iCCA therapy.

The patient (male, 52 years old) was diagnosed with advanced gastric cancer (cStage IV, cT4aN3M1 [LYM], por, HER2 0, microsatellite stable) and received docetaxel + cisplatin + S-1 (7 cycles), irinotecan + ramucirumab (11 cycles), and nivolumab (3 cycles), but experienced progressive disease (PD)...After three cycles of TAS-102, the patient experienced PD and provided consent for the off-label use of pemigatinib...To the best of our knowledge, this is the first reported case of pemigatinib therapy employed in a patient with advanced gastric cancer exhibiting FGFR2 gene alterations. This case could serve as a notable example of tumor-agnostic therapy to broaden treatment options for gastric cancer patients with rare genetic alterations.

P2, N=43, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2024 --> May 2025

P2, N=528, Active, not recruiting, Hoffmann-La Roche | N=790 --> 528

No abstract available

Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202.

P2, N=25, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=34, Completed, Innovent Biologics (Suzhou) Co. Ltd. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Aug 2023

Anti-FGFR treatment for cholangiocarcinoma (CCA) with fibroblast growth factor receptor (FGFR) alteration is a promising treatment option. In association with this reaction, cell cycle and mitosis were increased with GEM exposure in CCLP-1, but HuCCT1/CCLP-GR did not show this reaction. Our results suggested that combination therapy with GEM plus pemigatinib is a promising treatment for chemonaïve patients with CCA with activation of the FGF pathway.

"However, limited evidence has been presented to date for the efficacy of futibatinib in patients progressing under treatment with a non-covalent inhibitor. Between January 2021 and April 2023, 14 patients received futibatinib after treatment with the non-covalent FGFR inhibitors pemigatinib (10 patients) or derazantinib (4 patients). Futibatinib was manageable and active in patients with iCCA progressing under a previously non-covalent FGFR2 inhibitor. Randomized controlled trials are needed to determine the optimal therapeutic approach between an upfront treatment with a covalent inhibitor or a sequential strategy starting with a non-covalent inhibitor, followed by a covalent one if disease progresses due to acquired mutations that this could address."

P1/2, N=15, Completed, Yonsei University | Recruiting --> Completed | N=30 --> 15 | Trial completion date: Apr 2023 --> Aug 2023 | Trial primary completion date: Oct 2022 --> Aug 2023

New therapeutic areas for FGFR inhibition and drug failure mechanisms were identified across tumor types. ClinicalTrials.gov identifier: NCT03822117 .

P1, N=8, Terminated, Academic and Community Cancer Research United | Trial completion date: Jul 2025 --> Dec 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Dec 2023; Low accrual

P2, N=33, Not yet recruiting, Lund University Hospital

P1, N=70, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting

Currently, 3 targeted therapies are approved for use in CCA; Ivosidenib in patients with IDH1 mutations and Infigratinib/Pemigatinib in those with FGFR2 fusions. This is important, as it is thought up to 40 % of CCA patients harbour a potentially actionable mutation. In this review we provide an overview of the molecular pathogenesis of CCA and highlight currently available and potential future targeted treatments.

P2, N=10, Terminated, Incyte Corporation | Active, not recruiting --> Terminated; A business decision due to availability of commercial drug and other options for accessing study drug treatment.

P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025

FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.

Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Pemigatinib was recently approved for patients with relapsed or refractory FGFR1-rearranged neoplasms...Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. Mepolizumab, an interleukin-5 (IL-5) antagonist monoclonal antibody, is approved by the U.S Food and Drug Administration for patients with idiopathic HES. Cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. Targeted therapies such as the IL-5 receptor antibody benralizumab, IL-5 monoclonal antibody depemokimab, and various tyrosine kinase inhibitors for MLN-eo-TK, are under active investigation.