Tasfygo (tasurgratinib)

P1, N=72, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Dec 2024 --> Mar 2026 | Trial primary completion date: Dec 2024 --> Mar 2026

P2, N=63, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Sep 2024 --> Mar 2026 | Trial primary completion date: Sep 2024 --> Mar 2026

P1, N=18, Recruiting, Eisai Co., Ltd. | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2026

Part 1 included treatment with fulvestrant (FUL) 500 mg + E7090 (105 or 140 mg) or exemestane (EXE) 25 mg + E7090 (105 or 140 mg). These results emphasize that FGFR pathway activation evaluated with mRNA expression of selected genes at BL—rather than FGFR gene abnormalities—is a key molecular determinant for sensitivity to E7090, an FGFR inhibitor. Future validation of these biomarkers is necessary in a larger population of people with ER+/HER2− BC.

Five partial responses (83.3%) in cholangiocarcinoma patients and one partial response (11.1%) in gastric cancer patients were observed; median progression-free survival was 8.26 months (95% confidence interval [CI] 3.84, not evaluable [NE]) and 3.25 months (95% CI 0.95, 4.86), and overall survival was 22.49 months (95% CI 6.37, NE) and 4.27 months (95% CI 2.23, 7.95), respectively, in the two groups. In conclusion, Tasurgratinib 140 mg has a tolerable safety profile with good clinical efficacy in patients with cholangiocarcinoma harboring FGFR2 gene rearrangements.

P1, N=18, Recruiting, Eisai Co., Ltd. | Trial completion date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2024 --> Nov 2024

P2, N=46, Active, not recruiting, National Cancer Center, Japan | Recruiting --> Active, not recruiting

Tasurgratinib (E7090) is an orally available selective inhibitor of FGFR 1–3; the recommended dose is 140 mg per day per the dose-escalation part of a first-in-human phase 1 study...FGFR2 gene fusion was confirmed by fluorescence in situ hybridization performed in central laboratories; ≥ 1 prior chemotherapy regimen including a gemcitabine-based combination was required; pts treated with FGFR2 inhibitors were excluded... Tasurgratinib had promising antitumor activity in pts with CCA harboring FGFR2 gene fusion and who received ≥ 1 prior chemotherapy regimen. The primary endpoint (ORR) met the study’s predefined success criteria. Tasurgratinib had a manageable safety profile consistent with previous reports and with the known pharmacological profile of FGFR inhibitors.

The developed assay method was applied to a clinical trial of E7090, and plasma concentrations of E7090 and M2 were quantifiable up to 144 h postdose. These results indicated that the developed more sensitive assay was reproducible and was successfully applied to a clinical trial of E7090.

P1, N=72, Active, not recruiting, Eisai Co., Ltd. | Phase classification: P1b --> P1 | Trial primary completion date: Feb 2024 --> Dec 2024

P2, N=63, Active, not recruiting, Eisai Co., Ltd. | Trial primary completion date: Mar 2023 --> Sep 2024

P1, N=18, Recruiting, Eisai Co., Ltd. | Trial completion date: Nov 2023 --> Aug 2024 | Trial primary completion date: Nov 2023 --> Aug 2024

P1b, N=72, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Mar 2024 --> Dec 2024

P2, N=63, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Sep 2023 --> Sep 2024

For this, expression series GSE29231 (T2DM-adipose tissue), GSE70905 (BC- breast adenocarcinoma biopsies) and GSE150586 (diabetes and BC breast biopsies) were extracted from Gene Expression Omnibus (GEO) database, and analyzed to obtain differentially expressed genes (DEGs)...However, limitations associated with the insilico nature of this study necessitates for subsequent validation in wet lab. Hence, further investigation is crucial to study the molecular mechanisms of action underlying these genes to fully explore their potential as diagnostic and prognostic biomarkers and therapeutic targets for T2DM-BC association.

No abstract available

P1b, N=72, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting

Accuracy and precision were measured during the reproducibility assessments and were within ± 7.0% and 9.1%, respectively, in plasma and within ± 7.0% and 5.8%, respectively, in urine, indicating sufficient reproducibility. The validated methods were successfully applied to the quantification of E7090 in human plasma and urine to support a Phase-1 clinical trial.

P2, N=63, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting

A unique investigator-initiated multicenter Phase 2 trial was designed based on the results of preclinical investigation aiming to acquire the approval of E7090 for solid tumors harboring FGFR gene alterations. The findings may serve as a novel model for the development of tumor-agnostic molecular targeted therapies against rare genetic abnormalities.

P2, N=60, Recruiting, Eisai Co., Ltd. | Trial completion date: Dec 2022 --> Aug 2023 | Trial primary completion date: Jun 2022 --> Feb 2023

P2, N=45, Recruiting, National Cancer Center, Japan

P1, N=20, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Nov 2020 --> Jun 2021 | Trial primary completion date: Nov 2020 --> Jun 2021

E7090, an orally available FGFR1-3 selective inhibitor, is currently under evaluation in a Phase 2 study in patients with unresectable advanced or metastatic cholangiocarcinoma with FGFR2 gene fusion (NCT04238715), and a Phase 1 study as a monotherapy or in combination with fulvestrant (FUL) or exemestane for ER(+)/HER2(-) BC patients (NCT04572295). In this study, we present the roles of FGF/FGFR signaling in resistance to a CDK4/6 inhibitor and/or ET, and activities of E7090 on drug resistance in preclinical ER(+)/HER2(-) BC cell lines and PDx models. Antitumor activities of E7090 (25 or 50mg/kg, Q1Dx14 or x21, p.o.) were evaluated using five ER(+)/HER2(-) BC PDx models, OD-BRE-0438, -0450, -0188, -0704, and IM-BRE-556 with or without prior treatment of FUL (5 mg/mouse, Q7Dx2, s.c.)+palbociclib (PAL, 100mg/kg, Q1Dx14, p.o.)... In ER(+)/HER2(-) BC PDx models, FGFs/FGFRs expression in tumors were induced by treatment of FUL and/or PAL, and antitumor activity of E7090 was enhanced with prior FUL+PAL. In vitro study using cultured ER(+)/HER2(-) BC cell lines indicated that sensitivity against FUL or FUL+PAL was decreased by FGFR activation. Furthermore, a combination antitumor activity of E7090 and FUL was observed in the OD-BRE-0438 model.

P1b, N=102, Recruiting, Eisai Co., Ltd. | Not yet recruiting --> Recruiting | Trial completion date: Dec 2024 --> Apr 2024

Funding: Eisai. Clinical trial identification: NCT02275910.

P1b, N=102, Not yet recruiting, Eisai Co., Ltd.

Trial primary completion date: Apr 2020 --> Nov 2020

Lenvatinib (LEN) is a multi-targeted tyrosine kinase inhibitor that mainly inhibits VEGFR1-3 and FGFR1-4. Our results suggested that tumor FGF signals modulated immune response in TMEs through regulating interferon signal. Tumor FGF signal inhibition by LEN and E7090 may enhance antitumor immune response in the TMEs of that were immune suppressive with activated FGF signals. Further analyses will be warranted.

Trial completion date: Apr 2020 --> Nov 2020

In the first analysis, area of histological focal necrosis was greater in Hep3B2.1-7 xenograft tumors with the lenvatinib treatment than that after the treatment with sorafenib, which does not inhibit FGFRs. PD0325901, MEK inhibitor, caused the same changes in HCC cells as those described above for lenvatinib and E7090. These results reveal that the FGF signaling pathway through MAPK cascades plays an important role in survival of HCC cell lines with an activated FGF signaling pathway under limited nutrients, and FGFR-MAPK cascades likely contribute to survival of HCC cells with an activated FGF signaling pathway under tumor microenvironments with limited nutrients, where tumor angiogenesis is inhibited.

This study indicated that E7090 has a manageable safety profile in Part 2 and the promising clinical activity in CCA patients with FGFR2 gene fusion. Research Funding: Eisai co., Ltd