A Study of TAS-120 in Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT02052778
• Recruitment Status: Active, not recruiting
• First Posted: February 3, 2014
• Last Update Posted: May 4, 2021
• Sponsor: Taiho Oncology, Inc.
• Information provided by (Responsible Party): Taiho Oncology, Inc.

Tracking Information

• First Submitted Date: January 23, 2014
• First Posted Date: February 3, 2014
• Last Update Posted Date: May 4, 2021
• Actual Study Start Date: July 2014
• Estimated Primary Completion Date: May 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 19, 2018)

• Phase 1 - Overall Response Rate (ORR) [ Time Frame: 12 months ]
  Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors
• Phase 1 - Early Progression Rate (EPR) for GBM or grade III glioma [ Time Frame: 12 months ]
  Response assessments will be made based RANO for brain tumors
• Phase 2 - Overall Response Rate (ORR) [ Time Frame: 12 months ]
  Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors

Original Primary Outcome Measures (submitted: January 30, 2014)

• Safety and tolerability of TAS-120 [ Time Frame: Safety monitoring will begin at the time of the first dose of TAS-120, and will continue for 30 days after the last dose of TAS-120, until the initiation of another anticancer therapy, or up to 4 years, whichever occurs first. ]
  Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03) will be used. Assessed by number and severity of adverse events, physical exam, vital signs, weight, ECOG Performance Status, urinalysis, ophthalmological examination, neurological examination: electrocardiogram evaluation, hematology and coagulation, serum chemistry.
• Tumor assessments according to RECIST guidelines (version 1.1, 2009) [ Time Frame: Computed tomography scans will be performed at week 6, 12 and every 9 weeks thereafter until until treatment discontinuation, or up to 4 years, whichever occurs first. ]
  The determination of antitumor efficacy will be based on objective tumor assessments made by the investigator according to the revised RECIST guidelines (version 1.1, 2009) of unidimensional evaluation.
• Multiple Myeloma Assessments [ Time Frame: Multiple myeloma assessments for response will be conducted at the beginning of each cycle, i.e. every 3 weeks, until treatment discontinuation, or up to 4 years, whichever occurs first. ]
  Serum, urine protein electrophoresis and serum free light chain(SPEP/UPEP/SFLC) will be obtain to assess Multiple myeloma using The International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma (Durie et al, 2006).

Current Secondary Outcome Measures (submitted: March 19, 2018)

• Duration of Response (DOR) [ Time Frame: 12 months ]
  DOR is defined as time from first documentation of response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first
• Disease Control Rate (DCR) [ Time Frame: 12 months ]
  DCR is defined as proportion of patients with objective evidence of complete response, partial response or stable disease
• Progression free survival (PFS) [ Time Frame: 12 months ]
  PFS is defined as time from the day of first dose to the date of first objectively documented disease progression or death
• Patient Reported Outcome (PRO) [ Time Frame: 12 months ]
  PCR is define as the analysis of EQ-5D and EORTC QLQ-C30 from baseline through end of treatment
• Overall Survival (OS) [ Time Frame: 12 months ]
  OS is defined as date of first dose to death date in the safety population of Phase 1 and safety and efficacy population for phase 2

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of TAS-120 in Patients With Advanced Solid Tumors
• Official Title: Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

Brief Summary

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 3 parts, (1) Dose escalation to determine the MTD and/ or RP2D of TAS-120 in which this part of the study has been completed; (2) Phase 1 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. Up to approximately 185 patients will be enrolled in the phase 1 expansion; and (3) Phase 2 study to confirm ORR of TAS-120 in intra-hepatic CCA patients with tumors harboring FGFR2 gene fusions. Approx. 100 patients will be enrolled in phase 2.

Detailed Description

Phase 1 Dose Escalation Phase 1 Dose Escalation has been completed as of Dec 2017

Phase 1 Dose Expansion: (CLOSED)

Up to approximately 185 patients will be enrolled among the 8 groups as outlined below:

• Group 1- CCA (iCCA or eCCA) with FGFR2 gene fusions.
• Group 2- CCA (iCCA or eCCA) with FGFR2 gene fusions that are chemotherapy naive or intolerant to first line chemotherapy (i.e., on chemotherapy regimen ≤ 1 cycle).
• Group 3 - CCA (iCCA or eCCA) with FGFR2 gene fusions treated with prior FGFR inhibitors.
• Group 4 - CCA (iCCA or eCCA) with other FGFR2 abnormalities, ie, gene mutations, rearrangements or amplifications.
• Group 5 - GBM or grade III glioma (i.e, anaplastic astrocytoma or anaplastic oliogodendroglioma) with FGFR gene fusions or activating mutations
• Group 6 - Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations.
• Group 7: Basket of tumor types with tumors harboring FGFR2 amplification (≥10 copies).
• Group 8 - Basket of tumor types (except CCA, brain tumors and advanced urothelial carcinomas) with tumors harboring FGFR gene fusions or activating mutations.

Phase 2:

Approximately 100 iCCA patients with confirmed FGFR2 gene fusions will be treated. Patients will be centrally screened for FGFR2 gene fusions. This is a Single arm study with the primary endpoint of ORR.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cholangiocarcinoma
• Brain Tumor
• Urothelial Cancer
• Other Tumor Types With FGFR2 Gene Fusions
• Activating Mutations
• FGFR2 Amplification

• Intervention: Drug: TAS-120

Study Arms

Experimental: TAS-120

TAS-120 tablets, oral; 21-day cycle

Dose escalation portion of the study was completed.

Dose expansion- patients with tumors harboring specific FGFR aberrations, specifically in CCA, Brain Tumor , Urotherial carcinoma and any other tumors with FGFR fusion, activating mutation and amplification.

Phase 2- intra-hepatic CCA patients with tumors harboring FGFR2 gene fusions

Intervention: Drug: TAS-120

• Publications *: Bahleda R, Meric-Bernstam F, Goyal L, Tran B, He Y, Yamamiya I, Benhadji KA, Matos I, Arkenau HT. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors. Ann Oncol. 2020 Oct;31(10):1405-1412. doi: 10.1016/j.annonc.2020.06.018. Epub 2020 Jul 2.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 30, 2020): 386
• Original Estimated Enrollment (submitted: January 30, 2014): 835
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: May 29, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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

Phase 1 Expansion

1. Patient has failed all standard therapies or standard therapy does not exist or is not tolerated.

2. Patient has specific FGF/FGFR aberrations

   • Intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other FGFR2 abnormalities, i.e., gene mutations (see Appendix A), rearrangements or amplifications
   • Glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic oligodendroglioma) with FGFR gene fusions or activating mutations.
   • Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations
   • All other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (≥ 10 copies), FGFR gene fusions, or FGFR activating mutations

Phase 2

1. Patient has 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
2. Patient has been treated with and failed at least one prior systemic gemcitabine and platinum-based chemotherapy for the advanced disease
3. Must have documentation of radiographic progression of disease on prior systemic therapy
4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO criteria (2010) for brain tumors.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Adequate organ function

Exclusion Criteria:

A patient will be excluded from this study if any of the following criteria are met:

1. History and/or current evidence of non-tumor related alteration of calcium-phosphorus homeostasis.
2. History and/or current evidence of clinically significant ectopic mineralization/calcification.
3. History and/or current evidence of clinically significant retinal disorder confirmed by retinal examination.
4. A serious illness or medical condition(s)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Hong Kong, Japan, Korea, Republic of, Netherlands, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02052778
• Other Study ID Numbers: TPU-TAS-120-101; 2013-004810-16 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Taiho Oncology, Inc.
• Study Sponsor: Taiho Oncology, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Karim Benhadji, MD; Taiho Oncology, Inc.

• PRS Account: Taiho Oncology, Inc.
• Verification Date: April 2021