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: January 10, 2022
• 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: January 10, 2022
• Actual Study Start Date: July 2014
• Actual Primary Completion Date: May 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2021)

• Phase 1 (Dose escalation): Safety and Recommended Phase 2 Dose (RPTD) [ Time Frame: Baseline until 30 days after end of study treatment; up to 18 months (estimated) ]
• Phase 1 (Dose expansion): Objective Response Rate (ORR) [ Time Frame: Baseline to end of study treatment; up to 24 months (estimated) ]
• Phase 2 - Objective Response Rate (ORR) [ Time Frame: Baseline to end of study treatment; up to 24 months (estimated) ]
  Objective Response Rate (ORR) by independent review committee according to RECIST guidelines (version 1.1, 2009)

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: December 14, 2021)

• Phase 1 (Dose escalation): Pharmacokinetics [ Time Frame: Predose to Day 21 of cycle 1 ]
• Phase 1 (Dose escalation): Pharmacodynamics [ Time Frame: Predose to Day 21 of cycle 1 ]
• Phase 1 (Dose escalation): - Anti-tumor activity: Objective Response Rate (ORR) [ Time Frame: Baseline to end of study treatment; up to 24 months (estimated) ]
• Phase 1 (Dose expansion): Safety [ Time Frame: Baseline until 30 days after end of study treatment; up to 24 months (estimated) ]
• Phase 1 (Dose expansion): Disease Control Rate (DCR) [ Time Frame: Baseline to end of study treatment; up to 24 months (estimated) ]
• Phase 1 (Dose expansion): Duration of Response (DOR) [ Time Frame: From onset to end of confirmed response; up to 24 months (estimated) ]
• Phase 1 (Dose expansion): Progression free survival (PFS) [ Time Frame: Baseline until progressive disease or death; up to 24 months (estimated) ]
• Phase 1 (Dose expansion): Overall survival (OS) [ Time Frame: Baseline until death; up to 36 months (estimated) ]
• Phase 2: Duration of Response (DOR) [ Time Frame: From onset to end of confirmed response; up to 24 months (estimated) ]
• Phase 2: Safety [ Time Frame: Baseline until 30 days after end of study treatment; up to 24 months (estimated) ]
• Phase 2: Disease Control Rate (DCR) [ Time Frame: Baseline to end of study treatment; up to 24 months (estimated) ]
• Phase 2: Progression free survival (PFS) [ Time Frame: Baseline until progressive disease or death; up to 24 months (estimated) ]
• Phase 2: Overall survival (OS) [ Time Frame: Baseline until death; up to 36 months (estimated) ]
• Phase 2: Patient Reported Outcome (PRO) [ Time Frame: Baseline until 30 days after end of study treatment; up to 24 months ]

• 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 1/2 study for the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120). The purpose of the study is to evaluate the safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of futibatinib in patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities. The study will be conducted in 3 parts:

1. Dose escalation portion to determine the MTD and/ or RP2D of futibatinib.
2. Phase 1 expansion portion to further evaluate the safety and efficacy of futibatinib in patients with tumors harboring FGF/FGFR aberrations, including patients with cholangiocarcinoma (CCA), primary CNS tumors, urothelial carcinoma, breast cancer, gastric cancer.
3. Phase 2 study portion to confirm ORR of futibatinib in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cholangiocarcinoma
• Urothelial Cancer
• Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors
• Primary CNS Tumors
• Breast Cancer
• Gastric Cancer

Intervention

Drug: Futibatinib

oral once daily dosing, 21-day cycle

Other Name: TAS-120

Study Arms

• Experimental: Phase 1 Dose escalation
  Phase 1 Dose escalation portion for once daily and thrice weekly dosing of futibatinib (TAS-120) in patients with solid tumors.
  Intervention: Drug: Futibatinib
• Experimental: Phase 1 Dose expansion
  Phase 1 Dose expansion portion for once daily dosing of futibatinib (TAS-120) in patients with tumors harboring FGF/FGFR aberrations
  Intervention: Drug: Futibatinib
• Experimental: Phase 2
  Phase 2 portion for once daily dosing of futibatinib (TAS-120) in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions).
  Intervention: Drug: Futibatinib

• 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: June 30, 2022
• Actual Primary Completion Date: May 29, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Provide written informed consent
2. Age ≥ 18 years of age
3. Has histologically or cytologically confirmed, locally advanced or metastatic cancer

4. The following specific criteria for each study portion

   Phase 1 (Dose Escalation):

   • Patients with any type of solid tumor
   • Disease progression following standard therapies or intolerant to prior standard therapies

   Phase 1 (Dose Expansion)

   • Have at least one FGF/FGFR aberration
   • Disease progression following standard therapies or were intolerant to prior standard therapies (including prior FGFR inhibitors).
   • Have 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.

   • Patients with any of the following tumor types

     • Patients with intrahepatic or extrahepatic CCA harboring FGFR2 gene fusions or other FGFR2 aberrations
     • Patients with primary CNS tumors
     • Patients with advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations
     • Patients with breast cancer or gastric cancer
     • Patients with other solid tumor types harboring FGFR gene fusions or activating mutations
     • Patients with solid tumor types and other FGF/FGFR alterations not listed above

   Phase 2

   • Patients with iCCA and FGFR2 gene rearrangements (incl fusions)
   • Have been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy
   • Must have documentation of radiographic progression of disease
   • No prior FGFR inhibitor
   • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Adequate organ function.

Exclusion Criteria:

1. History and/or current evidence of clinically significant 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
4. A serious illness or medical condition(s)
5. Pregnant or breast-feeding female

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, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Spain, Taiwan, United Kingdom, United States
• Removed Location Countries: Portugal

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

• Plan to Share IPD: No

• Current Responsible Party: Taiho Oncology, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Taiho Oncology, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Taiho Oncology, Inc.
• Verification Date: January 2022