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A Study of TAS-120 in Patients With Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT04024436
Recruitment Status : Not yet recruiting
First Posted : July 18, 2019
Last Update Posted : July 18, 2019
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.

Brief Summary:
The purpose of this open-label, nonrandomized, Phase 2 study is to evaluate the efficacy and safety of TAS-120 and TAS-120 + fulvestrant in patients with locally advanced/metastatic breast cancer harboring FGFR gene amplifications.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer FGFR2 Amplification Drug: TAS-120 Drug: Fulvestrant Phase 2

Detailed Description:

Up to approximately 168 patients will be enrolled among the 4 cohorts as outlined below:

  • Cohort 1 - HR+ HER2- Measurable Disease w/ FGFR2 Amplification
  • Cohort 2 - TNBC Measurable Disease w/ FGFR2 Amplification
  • Cohort 3 - HR+ HER2- or TNBC Non-Measurable Disease w/ FGFR2 Amplification
  • Cohort 4 - HR+ HER2- Measurable Disease w/ FGFR1 Amplification

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) Amplifications
Estimated Study Start Date : August 30, 2019
Estimated Primary Completion Date : June 15, 2021
Estimated Study Completion Date : December 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arm Intervention/treatment
Experimental: TAS-120
TAS-120 tablets, oral; 28-day cycle
Drug: TAS-120
TAS-120 is an oral FGFR inhibitor
Other Name: Futibatinib

Experimental: TAS-120 + fulvestrant
TAS-120 tablets, oral; 28-day cycle Fulvestrant; intramuscular
Drug: TAS-120
TAS-120 is an oral FGFR inhibitor
Other Name: Futibatinib

Drug: Fulvestrant
Fulvestrant is used for the treatment of hormone receptor positive metastatic breast cancer




Primary Outcome Measures :
  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

  2. Clinical Benefit Rate (CBR) [ Time Frame: 12 months ]
    CBR is defined as the proportion of patients with a confirmed response of CR or SD lasting at least 24 weeks

  3. 6-month Progression-free Survival (PFS) rate [ Time Frame: 12 months ]
    The 6-month PFS rate is defined as the proportion of patients who are alive and progression-free 6 months after the first dose of study therapy


Secondary Outcome Measures :
  1. Complete Response (CR) [ Time Frame: 12 months ]
    CR is defined as the disappearance of all target and/or non-target lesions

  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

  3. Clinical Benefit Rate (CBR) [ Time Frame: 12 months ]
    CBR is defined as the proportion of patient with a confirmed response of CR, PR or SD lasting at least 24 weeks

  4. 6-month Progression-free Survival (PFS) rate [ Time Frame: 12 months ]
    6-month PFS rate is defined as the proportion of patients who are alive and progression-free 6 months after the first dose of study therapy

  5. Progression-free Survival (PFS) [ Time Frame: 12 months ]
    PFS is defined as the time from the first dose of study therapy to the date of death (any cause) or disease progression

  6. Duration of Response (DOR) [ Time Frame: 12 months ]
    DOR is defined as the time from first documentation of objective response to the date of death (any cause) or disease progression

  7. Overall Survival (OS) [ Time Frame: 12 months ]
    OS is defined as the time (in months) from the first dose of study therapy to the date of death (any cause)

  8. Number of Adverse Events (AEs) Related to TAS-120 as a monotherapy and in combination with Fulvestrant [ Time Frame: 12 months ]
    Standard safety monitoring and grading of treatment-emergent adverse events (AEs) will be performed using National cancer Institute (NCI)

  9. Number of Adverse Events (AEs) Related to TAS-120 as a monotherapy and in combination with Fulvestrant [ Time Frame: 12 months ]
    Standard safety monitoring and grading of treatment-emergent adverse events (AEs) will be performed using Common Terminology Criteria for Adverse Events (CTCAE - Version 5).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed recurrent locally advanced or metastatic breast cancer not amenable to treatment with curative intent, meeting all of the criteria for 1 of the following cohorts:

    A. Cohort 1 i. HR+ HER2- breast cancer harboring an FGFR2 gene amplification. HR+ HER2- breast cancer is defined per the local pathology report as estrogen receptor (ER) >1% and/or progesterone receptor (PR) >1%, HER2-negative per American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) guidelines, 2018.

    ii. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 iii. Has received 1-3 prior endocrine-containing therapies and up to 2 prior chemotherapy regimens for advanced/metastatic disease iv. Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such i. treatment (per Investigator decision) ii. Has experienced disease progression/recurrence within 1 month following the completion of any endocrine therapy for advanced/metastatic breast cancer

    B. Cohort 2 i. TNBC harboring an FGFR2 gene amplification. TNBC is defined as negative for ER, PR and HER2. Negative for ER and PR includes the following: local pathology report classifies them as negative, Allred Score of 2 or below or <1% staining. HER2-negative per ASCO / CAP guidelines, 2018.

    ii. Measurable disease per RECIST 1.1 iii. Has received at least 1 prior chemotherapy or chemotherapy/immunotherapy iv. (PD-L1/PD-1 inhibitors) regimen for advanced/metastatic disease Has experienced disease progression/recurrence during or after the most recent prior chemotherapy for advanced/metastatic breast cancer

    C. Cohort 3 i. TNBC or HR+ HER2- breast cancer (defined as above) harboring an FGFR2 gene amplification ii. Non measurable, evaluable disease per RECIST 1.1. Patients with bone-only disease must have lytic or mixed lytic-blastic lesions iii. Other criteria for either HR+ HER2- breast cancer or TNBC should be met as described for Cohort 1 and 2, respectively

    D. Cohort 4 i. HR+ HER2- breast cancer (defined as above) harboring an FGFR1 high-level gene amplification ii. Measurable disease per RECIST 1.1 iii. Has received 1-2 prior endocrine-containing therapies and no more than 1 prior chemotherapy regimen for advanced/metastatic disease. Prior treatment with fulvestrant is not permitted.

    iv. Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such i. treatment (per Investigator decision) ii. Pre/peri-menopausal patients must be on goserelin. Patients must have commenced treatment with goserelin or an alternative GnRH agonist at least 4 weeks prior to the first dose of fulvestrant. If patients have received an alternative GnRH agonist prior to study entry, they must switch to goserelin for the duration of the trial. Postmenopausal is defined as at least one of the following criteria: age ≥60 years; age <60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and follicle-stimulating hormone level within the laboratory's reference range for postmenopausal females; or documented bilateral oophorectomy.

    iii. Has experienced disease progression/recurrence within 1 month following the completion of any endocrine therapy for advanced/metastatic breast cancer.

  2. Archival or (preferably) fresh tumor tissue must be available for central laboratory confirmation of FGFR amplification.
  3. The patient has adequate organ function as defined by the following criteria:

    1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × the upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastases, AST and ALT ≤5 × ULN
    2. Total bilirubin ≤1.5 × ULN or ≤3 × ULN in case of Gilbert's syndrome
    3. Absolute neutrophil count (ANC) ≥1.0 × 109/L without hematopoietic growth factor support
    4. Platelet count ≥75 × 109/L without transfusion support (that is, excluding measurements obtained within 3 days after transfusion of platelets)
    5. Hemoglobin ≥9.0 g/dL without transfusion support (that is, excluding measurements within 7 days after transfusion of packed red blood cells or whole blood)
    6. Serum phosphorus ≤ ULN
    7. Creatinine clearance (calculated or measured value): ≥40 mL/min

Exclusion Criteria:

A patient must not meet any of the following exclusion criteria to be eligible for this study:

  1. History and/or current evidence of any of the following disorders:

    1. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator
    2. Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator
    3. Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator.
  2. Corrected QT interval using Fridericia's formula (QTcF) >470 msec. Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and the criterion does not apply.
  3. Treatment with any of the following within the specified time frame prior to the first dose of TAS-120:

    1. Major surgery within 4 weeks (the surgical incision should be fully healed)
    2. Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks
    3. Any prior systemic therapy regardless of the stop date, but the patient must have recovered to eligibility levels from prior toxicity
    4. Any investigational agent received within 30 days or 5 half-lives (whichever is shorter)
  4. Prior treatment with an FGFR inhibitor
  5. Cohort 4 only: Prior treatment with fulvestrant, or known hypersensitivity to fulvestrant.
  6. A serious illness or medical condition(s) including but not limited to the following:

    1. Known acute systemic infection
    2. Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the previous 6 months
    3. History or current evidence of serious uncontrolled ventricular arrhythmia
    4. Chronic diarrhea diseases considered to be clinically significant in the opinion of the Investigator
    5. Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death
    6. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or TAS-120 administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study
  7. Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month)
  8. History of another primary malignancy that is currently clinically significant or currently requires active intervention
  9. Pregnant or lactating female

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04024436


Contacts
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Contact: Karim Benhadji, MD 609-285-5232 KBenhadji@taihooncology.com

Locations
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United States, Texas
UT Southwestern Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Nisha Unni, MD    214-648-4180    Nisha.Unni@UTSouthwestern.edu   
Contact: Melanie Hullings    214-648-7097    Melanie.Hullings@UTSouthwestern.edu   
Sponsors and Collaborators
Taiho Oncology, Inc.

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Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04024436     History of Changes
Other Study ID Numbers: FOENIX-MBC2 TAS-120-201
2019-001164-30 ( EudraCT Number )
First Posted: July 18, 2019    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Taiho Oncology, Inc.:
Futibatinib
Metastatic Breast Cancer
FGFR
TAS-120
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs