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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Bladder Cancer, NMIBC, Non-Muscle Invasive Bladder Cancer, Urothelial Carcinoma Recurrent

Intervention / Treatment
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* Drug: Pemigatinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder Cancer, Non Muscle Invasive Bladder Cancer, Non-Muscle Invasive Bladder Cancer (NMIBC), NMIBC, Urothelial Carcinoma, Urothelial Cancer, Urinary Bladder Neoplasm, Bladder Neoplasm, Fibroblast inhibitors, Pemigatinib, FGFR inhibitor