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Taiho TPU-TAS-120-101: Phase 1/2 study of TAS-120 in patients with advanced solid tumors harboring FGF/FGFR aberrations

Description

This is an open-label, nonrandomized, phase 1 dose escalation, dose expansion and phase 2 study targeting tumors with FGF/FGFR aberrations. The purpose of the study is to evaluate the safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of TAS-120 in patients with advanced solid tumors with and without FGF/FGFR-related abnormalities.

The study will be conducted in three parts. 

Part 1: Phase 1 dose escalation has been completed. 

Part 2: Phase 1 dose expansion to further evaluate the safety and efficacy of RP2D of TAS-120 in patients with tumors harboring specific FGFR aberrations, specifically in patients with cholangiocarcinoma, gliomas, urothelial carcinomas and any other tumors with FGFR fusion or activating mutation or amplification. 

Part 3: Phase 2 intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 gene fusions.

Status

Accepting new patients

Primary Study Objective(s)

The primary objective of the phase 1 expansion are:

  • To evaluate the Overall Response Rate (ORR) in cholangiocarcinoma (intra-hepatic [iCCA] or extra-hepatic [eCCA]) patients with tumors harboring FGFR2 gene fusions
  • To evaluate ORR in cholangiocarcinoma (intra-hepatic [iCCA] or extra-hepatic [eCCA]) patients with other FGFR abnormalities
  • To evaluate ORR and early progression rate (EPR) (defined as progression-free rate at the end of Cycle 2) in glioblastoma multiforme (GBM) or grade III glioma (i.e., anaplastic astrocytoma or anaplastic oligodendroglioma) patients with tumors harboring FGFR gene fusions or activating mutations
  • To evaluate ORR in patients with advanced urothelial carcinoma with tumors harboring FGFR3 gene fusions or FGFR3 activating mutations
  • To evaluate ORR in a basket of tumor types with tumors harboring FGFR2, FGF9 or FGF19 amplifications
  • To evaluate ORR in a basket of tumor types (except CCA, brain tumors and advanced urothelial carcinoma that are included in other groups) with tumors harboring FGFR gene fusions or activating mutations

The phase 2 primary objective is to confirm the overall response rate in iCCA patients with FGFR2 gene fusions based on independent central radiology review.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Phase 1 expansion

Including patients who:

Have histologically or cytologically confirmed, locally advanced, metastatic cancer meeting the following criteria:

  • The patients have failed all standard therapies or standard therapy does not exist or is not tolerated.
  • The patients have specific FGF/FGFR aberrations.
  • The patients have intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other FGFR2 abnormalities,i.e., gene mutations (see Appendix A), rearrangements or amplifications.
  • The patients have glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic oligodendroglioma) with FGFR gene fusions or activating mutations.
  • The patients have advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations.
  • Patients have other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (≥ 10 copies), FGFR gene fusions, or FGFR activating mutations.

Phase 2

Including patients who:

  • Have a histologically or cytologically confirmed, locally advanced, metastatic, unresectable iCCA harboring FGFR2 gene fusions based on results from a NGS assay by the sponsor's designated central laboratory
  • Have been treated with and failed at least one prior systemic gemcitabine and platinum-based chemotherapy for the advanced disease
  • Have documentation of radiographic progression of disease on prior systemic therapy
  • Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for advanced solid tumors or RANO criteria (2010) for brain tumors
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Have adequate organ function

  • Excluding patients who:
  • Have a history and/or current evidence of non-tumor related alteration of calcium-phosphorous homeotasis.
  • Have a history and/or current evidence of clinically significant ectopic mineralization/calcification.
  • Have a history and/or current evidence of clinically significant retinal disorder confirmed by a retinal examination.
  • Have a serious illness or medical condition(s)