Studienregister der Deutschen Gesellschaft für Urologie e.V.

INCYTE - INCB 54828-201

INCB 54828-2012016-001321-14NCT02872714

A Phase 2, Open-Label, Single-Agent, Multicenter Study to Evaluate the Efficacy and Safety of INCB054828 in Subjects With Metastatic or Surgically Unresectable Urothelial Carcinoma Harboring FGF/FGFR Alterations

Status: Active (Recruitment Closed)

Purpose / Objectives

Primary Outcome

  • Objective response rate in subjects with FGFR3 mutations or fusions based on central genomics laboratory results (Cohort A).  Response will be based on review of scans by a centralized radiological review committee.



Secondary Outcomes

  • Objective response rate in all subjects with FGFR3 mutations or fusions and all other FGF/FGFR alterations and (Cohorts A and B combined).
  • Objective response rate in subjects with all other FGF/FGFR alterations (Cohort B).
  • Progression-free survival (both cohorts).
  • Duration of response (both cohorts).
  • Overall survival (both cohorts).
  • Safety and tolerability assessed by evaluating the frequency, duration, and severity of adverse events (AEs); through review of findings of physical examinations, changes in vital signs, and electrocardiograms; and through clinical laboratory blood and urine sample evaluations.



Metastatic or Surgically Unresectable Urothelial Carcinoma

Harboring FGF/FGFR Alterations



Patient attributes



Inclusion criteria

1.   Men and women, aged 18 or older.

2.   Histologically documented metastatic or surgically unresectable urothelial

      carcinoma (Stage IIIB or IV per the American Joint Committee on Cancer

       (AJCC 2010); may include Primary site from ureters, upper tract, renal

       pelvis, and bladder.

3.   ECOG performance status of 0, 1, or 2.

4.   Life expectancy ≥ 12 weeks.

5.   Radiographically measurable disease per RECIST v1.1.

6.   Documented FGF/FGFR alteration (see Appendix C) and either:

a.   have failed at least 1 previous treatment for their metastatic or surgically

      unresectable urothelial carcinoma (ie, chemotherapy, immunotherapy), or

b.   have not received chemotherapy for metastatic or surgically unresectable

      urothelial carcinoma due to poor performance status (ie, ECOG

       performance status of 2) and insufficient renal function (ie, creatinine

       clearance < 60 mL/min or local guidelines).

7.   Archival tumor specimen (tumor block or 25 unstained slides, minimum

      number of slides is 15) or willingness to undergo a pretreatment tumor

      biopsy to provide a tumor block or 25 unstained slides (minimum number

      of slides is 15). Archival tumor biopsies are acceptable at baseline and

      should be no more than 2 years old (preferably < 1 year old and collected

       since the completion of the last treatment); subjects with a sequencing

      report of their tumor from the sponsor's central laboratory within 2 years

      are exempt from the need for tumor biopsy, but a tumor sample should be

      provided to the Sponsor is available.

8.   Willingness to avoid pregnancy or fathering children based on the criteria


a.   Woman of nonchildbearing potential (ie, chemically sterile, surgically

      sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months

      of amenorrhea).

b.   Woman of childbearing potential who has a negative pregnancy test

      (serum and/or urine) at screening and before the first dose on Day 1 and

      who agrees to take appropriate precautions to avoid pregnancy (with at

      least 99% certainty) from screening through 90 days after last dose of

      study drug. Permitted methods that are at least 99% effective in

      preventing pregnancy (see Appendix A) should be communicated to the

      subject and their understanding confirmed.

c.   Men who agree to take appropriate precautions to avoid fathering children

      (with at least 99% certainty) from screening through 90 days after last

      dose of study drug. Permitted methods that are at least 99% effective in

      preventing pregnancy (see Appendix A) should be communicated to the

      subject and their understanding confirmed.


Exclusion criteria

1. Treatment with other investigational study drug for any indication for any

    reason, or receipt of anticancer medications within 28 days before first dose

    of study drug. Subjects must have recovered (Grade ≤ 1 or at pretreatment

    baseline) from AEs from previously administered therapies.

2. Untreated brain or central nervous system (CNS) metastases or brain/CNS

    metastases that have progressed (eg, evidence of new or enlarging brain

    metastasis or new neurological symptoms attributable to brain/CNS

    metastases). Subjects with previously treated and clinically stable

    brain/CNS metastases and who are off all corticosteroids for ≥ 4 weeks are


3. Known additional malignancy that is progressing or requires active

    treatment. Exceptions include basal cell carcinoma of the skin, squamous

    cell carcinoma of the skin, carcinoma in situ of the cervix, or other

    noninvasive or indolent malignancy that has undergone potentially curative


4. Are pregnant or lactating.

5. Prior receipt of a selective FGFR inhibitor.

6. Abnormal laboratory parameters:

a. Total bilirubin ≥ 1.5 × upper limit of normal (ULN; ≥ 2.5 × ULN if Gilbert

    Syndrome or metastatic disease involving liver).

b. AST and ALT > 2.5 × ULN (AST and ALT > 5 × ULN in the presence of liver


c. Creatinine clearance ≤ 30 mL/min based on Cockroft-Gault.

d. Serum phosphate > institutional ULN.

e. Serum calcium outside of the institutional normal range or serum albumin-

    corrected calcium outside of the institutional normal range when serum

    albumin is outside of the institutional normal range.

7. History of calcium/phosphate homeostasis disorder.

8. History of human immunodeficiency virus infection.

9. Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) active

     infection or risk of

10. History or presence of an abnormal ECG that in the investigator's opinion

      is clinically meaningful. A screening QTcF interval > 450 milliseconds is


11. History of clinically significant or uncontrolled cardiac disease, including

      unstable angina, acute myocardial infarction, New York Heart Association

      Class III or IV congestive heart failure, or arrhythmia requiring therapy.

      Subjects with a pacemaker and well-controlled rhythm for at least 1 month

      before first dose will be allowed.

12. Have undergone major surgical procedure other than for diagnosis within

      28 days before Cycle 1 Day 1.

13. Inadequate recovery from toxicity and/or complications from a major

      surgery before starting therapy.

14. Pregnant or nursing women or subjects expecting to conceive or father

      children within the projected duration of the study, starting with the

      screening visit through completion of safety follow-up visit.

15. Concurrent anticancer therapy (eg, chemotherapy, radiation therapy,

      surgery, immunotherapy, biologic therapy, hormonal therapy,

      investigational therapy, or Tumor embolization).

16. Received prior radiation therapy administered within 4 weeks of first dose

      of study drug. Subjects must have recovered from all radiation-related

      toxicities, not require corticosteroids, and not have had radiation

      pneumonitis. A 2-week washout is permitted for palliative radiation to non-

      CNS disease.

17. History and/or current evidence of ectopic mineralization/calcification,

      including but not limited to soft tissue, kidneys, intestine, myocardia, or

      lung, excepting calcified lymph nodes and asymptomatic arterial or

      cartilage/tendon calcification.

18. Current evidence of corneal disorder/keratopathy, including but not limited

      to bullous/band keratopathy, corneal abrasion, inflammation/ulceration,

      keratoconjuctivitis, etc, confirmed by ophthalmologic examination.

19. Current use of prohibited medication as described in Section 5.6.2.

20. Use of any potent CYP3A4 inhibitors or inducers (see Appendix B) within

      14 days or 5 half-lives (whichever is shorter) before the first dose of study


21. Known hypersensitivity or severe reaction to INCB054828 or excipients of

      INCB054828 study drug (refer to the IB).

22. Inability or unlikeliness to comply with the dose schedule and study

       evaluations, in the opinion of the investigator.

23. Inability to comprehend or unwilling to sign the ICF.

24. Inability or unwillingness to swallow INCB054828 or significant

      gastrointestinal disorder(s) that could interfere with the absorption,

       metabolism, or excretion of

25. Subjects who require hemodialysis.

26. Any condition that would, in the investigator's judgment, interfere with full

      participation in the study, including administration of study drug and

      attending required study visits; pose a significant risk to the subject; or

      interfere with interpretation of study data.

27. Subjects with history of hypovitaminosis D requiring supraphysiologic

     doses to replenish the deficiency. Subjects receiving vitamin D food

     supplements are allowed.

Trial design

  • Phase II
  • Multicenter
  • Retrospective
  • One-arm
  • Open Label


INCB054828 will be self-administered as a QD oral treatment on a 21-day

cycle. Subjects will take study drug for 2 weeks continuously (14 days)

followed by a 1-week (7 days) break. The starting dose will be 13.5 mg. Each

dose of study drug should be taken immediately upon rising or after a 2-hour

fast. Subjects should plan to fast for 1 additional hour after taking study drug.

Documents (password protected)

Responsibilities in overall trial

Incyte Corporation

National Coordinating Investigator

Prof. Dr. med. Arnulf Stenzl



    Isabel Vogt

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