A Study of Pemigatinib in Non-muscle Invasive Bladder Cancer Patients With Recurrent Low- or Intermediate-Risk Tumors

Phase 2 Window of Opportunity Study of Pemigatinib in Non-muscle Invasive Bladder Cancer Patients With Recurrent Low- or Intermediate-Risk Tumors

This phase II trial studies how well Pemigatinib (an orally administered inhibitor of fibroblast growth factor receptors 1, 2, and 3) works in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors and a prior history of low- or intermediate-risk NMIBC tumors. Participants will receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).

Study Overview

• Status: Completed
• Conditions: Bladder Cancer; NMIBC; Urothelial Carcinoma Recurrent; Non-Muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: Pemigatinib

Detailed Description

It is a single-arm phase 2 window of opportunity study to assess the antineoplastic activity of pemigatinib in non-muscle invasive bladder cancer (NMIBC) patients with recurrent tumors and a prior history of low- or intermediate-risk NMIBC tumors. Enrolled patients will receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT). The primary endpoint will be complete response rate as determined at TURBT. Secondary endpoints will include safety profile, associations between complete response rate and tumor mutation/fusion status (e.g. FGFR3 specifically, others will also be examined) and NMIBC risk group (low- vs. intermediate-risk), and assessment of pemigatinib post-treatment urothelial tissue concentrations. The study will be conducted at 4-5 high volume bladder cancer institutions within the US and managed through the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center clinical research office.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
  • New York
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals Urology
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • MidLantic Urology
    • Lancaster, Pennsylvania, United States, 17604
      • Keystone Urology
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prior histologically confirmed low- or intermediate-risk non-muscle invasive urothelial carcinoma of the bladder (NMIBC) defined according to the following characteristics:

  • Low Risk

    • Initial tumor with all of the following:
    • Solitary tumor
    • Ta tumor
    • Low-grade
    • <3 cm
    • No CIS

  • Intermediate Risk

    --- All tumors not defined in the two adjacent categories (between the category of low- and high-risk)

  • High Risk

    • T1 tumor
    • High-grade
    • CIS
    • Multiple and recurrent and large (>3 cm) Ta low-grade tumors (all conditions must be met for this point on Ta low-grade tumors)
• Documented tumor recurrence as noted in standard of care follow up cystoscopy.
• ECOG (WHO) performance status 0-2
• Age ≥ 18 years old

• Patients must have the following laboratory values:

  • White blood cell count (WBC) > 3.0 K/mm3
  • Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
  • Platelets ≥ 100 K/mm3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Serum total bilirubin: ≤ 1.5 x ULN
  • ALT and AST ≤ 3.0 x ULN
  • Serum calcium < ULN
  • Serum phosphate < ULN
  • Serum creatinine ≤ 1.5 x ULN or serum creatinine > 1.5 - 3 x ULN if calculated creatinine clearance (CrCl) is ≥ 30 mL/min using the modified Cockcroft-Gault equation
• Patients who give a written informed consent obtained according to local guidelines

Exclusion Criteria:

• Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma.
• Patients with high grade urothelial carcinoma on their most recent urine cytology.
• Patients with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. (Patients that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.)
• Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Patients who have received prior selective fibroblast growth factor receptor targeting agents (i.e. pemigatinib, dovitinib, BGJ398, AZD4547, JNJ-42756493, etc.).
• Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment: Pemigatinib; Patients will receive pemigatinib for 4 to 6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).	Drug: Pemigatinib; Participants will take Pemigatinib once daily on days 1 through 28 of each cycle prior to standard of care TURBT.; Other Names: INCB054828; FGFR inhibitor INCB054828

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate of pemigatinib therapy	The number of participants with a complete response to pemigatinib therapy. Tumor complete response is defined as the complete absence of any stage bladder tumor on post-treatment Transurethral Resection of a Bladder Tumor (TURBT) and no evidence of recurrent urothelial carcinoma on post-treatment urine cytology.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the safety profile of pemigatinib therapy	Number of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 toxicities	4 years
Number of Participants with Complete Response and FGFR3 Mutational Status		Up to 4 weeks
Number of Participants with Non-Muscle Invasive Bladder Cancer (NMIBC) and Complete Response	Number of participants with complete response rate and baseline NMIBC risk group (low- vs. intermediate-risk)	Up to 4 years
Maximal concentration (Cmax, nmol/L) of pemigatinib in urothelial tissue at post-treatment TURBT		Up to 4 weeks
Relapse Free Survival (RFS) at 6 months	Number of months from achieving a complete response at initial post-treatment TURBT until relapse.	6 months
Relapse Free Survival (RFS) at 12 months	Number of months from achieving a complete response at initial post-treatment TURBT until relapse.	12 months
Relapse Free Survival (RFS) at 24 months	Number of months from achieving a complete response at initial post-treatment TURBT until relapse.	24 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: Noah M Hahn, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2020
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): September 30, 2025

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: April 11, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Urothelial Carcinoma; NMIBC; Bladder Cancer; Bladder Neoplasm; Urothelial Cancer; Non Muscle Invasive Bladder Cancer; Non-Muscle Invasive Bladder Cancer (NMIBC); FGFR inhibitor; Pemigatinib; Urinary Bladder Neoplasm; Fibroblast inhibitors
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; pemigatinib
• Other Study ID Numbers: J18158; IRB00194271 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No