Pemazyre (pemigatinib)

They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAFV600E mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms...For example, BRAFV600E and IDH1/2 mutations; ALK, FGFR, and NTRK fusions; PD-L1 amplification; and CD70 antigens are druggable in both solid and blood malignancies by gene-/immune-targeted therapies/chimeric antigen receptor T cells. Future biomarker-based tissue-agnostic basket studies/approvals should bridge the great divide and include both solid and hematologic cancers.

P2, N=38, Not yet recruiting, Mehmet Akce

The patient was treated with pemigatinib (a selective FGFR inhibitor) in combination with Gemcitabine and Cisplatin at our hospital. To the best of our knowledge, this is the first reported rare case of unresectable cHCC-CCA with FGFR2-PRDM16 fusion in a child successfully treated with a combination of pemigatinib and chemotherapy as a first-line regimen. This treatment combination may be effective and safe for patients with unresectable cHCC-CCAs.

Currently, pemigatinib and futibatinib are FDA approved FGFR-targeted therapies that have demonstrated remarkable responses. Additionally, unique side effects of FGFR inhibitors may limit their efficacy in clinical practice and can have detrimental effects on quality of life. Several novel FGFR inhibitors are currently being investigated to overcome resistance mechanisms and reduce toxicities.

It is found that although 5-fluorouracil, cisplatin, pemigatinib, and gemcitabine all inhibit ICC-TRCs, sulfarotene demonstrates superior efficacy. These actions collectively inhibit ICC-TRCs via destroying PSGL1-regulated cytoskeleton. The findings provide a strategy of inhibiting P-selectin/PSGL1 interaction and altering PSGL1 glycosylation pattern to compromise the cytoskeletal integrity and eliminate ICC-TRCs.

For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

We report three patients with histiocytic disorders harboring novel alterations who had sustained responses to off-label kinase inhibitors specific to their histiocytic disorder. Pathogenic variants outside of the MAPK pathway, including variants of unknown significant, may be targeted with readily available small molecules.

This review provides practical insights for advanced practice providers on the management of these common AEs associated with selective FGFR inhibitors in the real-world setting, focusing on pemigatinib and futibatinib. Impacts of renal or hepatic impairment, drug-drug interactions, and drug-food interactions are discussed. Also presented are practical recommendations for prophylaxis and supportive care measures, and resources for health-care professionals and patients.

P2, N=47, Completed, Incyte Corporation | Active, not recruiting --> Completed

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.

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.

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.

P2 | "The most frequently assigned TTs were IPI/NIVO (37%), ipatasertib (16%), pemigatinib (8%), TDM1 (8%), and atezo/ipatasertib (6%). The incidence of G≥3 AEs was 35% for TT and 40% for SoC. Conclusions 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