Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

The purpose of the trial is to evaluate a response to combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor futibatinib and anti-programmed cell death-1 (PD-1) antibody pembrolizumab in patients with advanced or spreading urothelial cancer who are not candidates to receive a platinum-based treatment regimens. It also will help us to learn about the side effects of this combination therapy. This study will also help us to find the futibatinib and pembrolizumab predictive markers of response (i.e. benefit from specific treatment; helps to select particular treatment over another). Another objective is to evaluate the supposed futibatinib and pembrolizumab combination's immunomodulatory effects (i.e. Drug that modifies the immune response or the functioning of the immune system as by the stimulation of antibody formation or the inhibition of white blood cell activity). By conducting this study, we will learn about the variability in drug concentrations within a patient population receiving clinically relevant doses of a futibatinib and pembrolizumab. Pharmacokinetics allows us to examine how the body processes a drug.

Official Title

A Phase 2 Study Evaluating Futibatinib (TAS 120) Plus Pembrolizumab in the Treatment of Advanced or Metastatic Urothelial Carcinoma

Details

This study is an open-label, nonrandomized, multicenter Phase 2 study evaluating the combination of futibatinib and pembrolizumab in patients with advanced or metastatic UC who are not candidates to receive a platinum-based treatment regimen. Approximately 46 subjects advanced or metastatic Urothelial Cancer (UC) will be enrolled in the trial at approximately 15-17 sites worldwide: - 6 patients in the safety lead-in - 20 patients with tumors characterized by specific genetic abnormalities (Cohort A) - 20 patients with tumors not characterized by specific genetic abnormalities (Cohort B). A treatment cycle is defined as 21 days. All enrolled participants will receive the same treatment - Futibatinib at an oral (PO) dose of 20 mg daily (5 tablets) (QD); and - Pembrolizumab at an intravenous (I.V.) dose of 200 mg every 3 weeks (Q3W). Treatment will continue until disease progression, unacceptable side effects, or any other of the criteria for treatment discontinuation is met; of note, pembrolizumab may be administered for a maximum of 35 doses or a maximum duration of 2 years, whichever is earlier. The study will begin with a safety lead-in period. During this period, a total of 6 patients with advanced or metastatic urothelial carcinoma will be enrolled and treated for at least one 21-day cycle. Patients will be enrolled into this initial safety lead-in period without regard for FGFR alteration status.

Keywords

Advanced and Metastatic Urothelial Cancer Futibatinib Pembrolizumab Urothelial cancer FGFR TAS120 MK3475 B04 Carcinoma, Transitional Cell Futibatinib and Pembrolizumab

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Histologically confirmed advanced or metastatic urothelial carcinoma who have not received systemic treatment for advanced metastatic disease. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting.
  2. Cohort A: must have an FGFR3 mutation or FGFR1-4 fusion/rearrangement.
  3. Cohort B: all other patients with UC (including patients with other FGFR or non-FGFR genetic aberrations and patients with wild-type [non-mutated] tumors)
  4. Unfit for or intolerant to standard platinum-based chemotherapy as defined by any one of the following criteria:
  5. Chronic kidney disease characterized by the estimated creatinine clearance rate (eCCr) per Cockcroft-Gault formula of <60 mL/min or estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, corresponding to NCI-CTCAE v.5.0 Grade ≥2
  6. Impaired hearing (measured by audiometry) of >25 decibel (dB) at two contiguous test frequencies in at least one ear, corresponding to NCI-CTCAE v.5.0 Grade ≥2
  7. Peripheral sensory neuropathy Grade ≥2 by NCI-CTCAE v.5.0
  8. In the opinion of the Investigator, the patient is considered ineligible to receive any platinum-based chemotherapy
  9. Be willing and able to provide written informed consent for the trial.
  10. Be ≥ 18 years of age.
  11. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
  12. Adequate organ function as defined by the following criteria:
  13. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
  14. Platelet count ≥ 100,000/mm3
  15. Hemoglobin ≥ 9.0 g/dL
  16. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT ≤ 5.0 × ULN.
  17. Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert's syndrome.
  18. Creatinine clearance (Ccr) (calculated or measured value): ≥30 mL/min. For calculated Ccr, use the Cockcroft-Gault formula.
  19. International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or Activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
  20. Phosphorus <1.5 ULN
  21. Have a measurable disease per RECIST 1.1, as assessed by the local site Investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

You CAN'T join if...

  1. Have received prior therapy with anti-PD-1, anti-PD-L1/L2 agent or FGFR inhibitor.
  2. History and/or current evidence of any of the following disorders:
  3. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator
  4. 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
  5. Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator.
  6. Has received major surgery within the previous 4 weeks.
  7. Has received any non-investigational anticancer therapy within the previous 3 weeks (mitomycin within the previous 5 weeks).
  8. Is currently participating in a study of an investigational agent/device, or has participated in a study of an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment.
  9. Has received a live vaccine within 30 days prior to the first dose of study drug.

Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.

  1. Have an active autoimmune disease that has required systemic treatment in the past 2 years (that is, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (for example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  2. Have a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
  3. Have had an allogenic tissue/ organ transplant.
  4. . Has known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative Hepatitis C virus (HCV) RNA results greater than the lower limits of detection of the assay.
  5. . Have known active central nervous system metastases and/or carcinomatous meningitis.
  6. . Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
  7. . Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
  8. . Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients

Locations

  • UCSF Helen Diller Family
    San Francisco California 94158 United States
  • Henry Ford Hospital
    Detroit Michigan 48202 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Taiho Oncology, Inc.
ID
NCT04601857
Phase
Phase 2
Study Type
Interventional
Last Updated