Pemazyre (pemigatinib)

Pemigatinib plus paclitaxel demonstrated antitumor activity with an acceptable safety profile in FGFR2-amplified gastric cancer. Further investigation is warranted to elucidate resistance mechanisms and validate these findings in larger cohorts.

The most common baseline regimen was gemcitabine + cisplatin (34.4%). Treatment patterns, adherence, OS, HCRU, and costs demonstrated consistent trends across racial subgroups. Real-world pemigatinib treatment patterns and survival outcomes were consistent with findings from clinical trials and support continued use of pemigatinib across diverse patient groups as a key second-line treatment for CCA.

P2, N=24, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting

Functional analyses demonstrated that ARRB2 promotes the malignant progression of ICC by facilitating YAP nuclear translocation while also modulating the sensitivity of ICC to pemigatinib through the Raf-MEK-ERK signaling axis. This study identifies the tumor-promoting activities of ARRB2 and elucidates the regulatory mechanism of the METTL3-ARRB2-YAP/Raf axis in ICC, which may provide a novel prognostic biomarker and potential therapeutic target for human ICC.

The incidence of FGFRi-associated nail toxicities varies by agent and can affect quality of life and treatment adherence. The pathogenesis remains unclear, and no predictive biomarkers exist. Further research into optimized management and preventative strategies is needed. Early recognition and proactive multidisciplinary management are essential to minimizing complications and maintaining oncologic treatment continuity. &nbsp.

Outside allogeneic stem cell transplantation (ASCT), survival with conventional therapy is dismal, representing an unmet clinical need. We summarize here the data that led to approval of pemigatinib, a FGFR1 inhibitor, showing unprecedented efficacy in M/LN-FGFR1.

P2, N=24, Not yet recruiting, Dana-Farber Cancer Institute

Selective FGFR tyrosine kinase inhibitors, including the reversible inhibitor pemigatinib and the irreversible inhibitor futibatinib, have demonstrated clinically meaningful response rates and durable disease control in patients with previously treated FGFR2-altered iCCA, leading to regulatory approvals and the incorporation of FGFR inhibition into contemporary treatment paradigms. In addition, we highlight the growing role of circulating tumor DNA as a noninvasive tool for longitudinal molecular monitoring and treatment guidance. Together, these insights underscore the central role of FGFR2-directed therapy in precision oncology for biliary tract cancer and provide a framework for optimizing and extending targeted treatment in this molecularly defined disease subset.

Adding ivosidenib to gemcitabine and cisplatin in this study demonstrated a challenging safety profile in advanced CCA. Further research and dose optimization are warranted to confirm these findings and optimize the integration of targeted therapies into first-line regimens.

Subsequent administration of the irreversible FGFR1-4 inhibitor futibatinib was associated with a declining trend in tumor biomarkers, indicating preliminary antitumor activity against the resistant clone. This case underscores the clinical activity of FGFR inhibition in FGFR2-altered SGC and exemplifies the emergence of kinase domain mutations as a principal resistance pathway. It further suggests that irreversible FGFR inhibitors may represent a rational therapeutic strategy upon progression on prior FGFR-directed therapy, warranting further clinical investigation in this molecularly defined patient subset.

Recent development of selective FGFR inhibitors-such as pemigatinib, erdafitinib, and futibatinib-has translated mechanistic insights into measurable clinical benefits in genomically defined patient populations. This review also highlights emerging therapeutic modalities, such as antibody-drug conjugates and nanotechnology-based delivery systems, which may improve target specificity and prolong therapeutic durability. By integrating molecular, translational, and clinical evidence, this review aims to establish a comprehensive framework for precision oncology strategies targeting FGFR-driven malignancies.

Genetic silencing and pharmacological inhibition of RORγ (GSK805/XY101) suppressed proliferation, induced apoptosis in vitro, and significantly reduced xenograft tumor growth in vivo. Notably, RORγ antagonists synergized with pemigatinib to overcome resistance in pemigatinib-refractory models. Collectively, these findings identify the RORγ-FGF1-FGFR2 axis as a critical oncogenic driver in iCCA and highlight RORγ inhibition as a promising therapeutic strategy to suppress tumor progression and enhance sensitivity to FGFR inhibitors.