Safety and Efficacy of Pemigatinib in Patients With High-risk Urothelial Cancer After Radical Surgery

NCT04294277 | Terminated Phase 2 Results DMC

• 1 other identifier: EAU RF 2018-02
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this clinical trial is to demonstrate the benefit of Pemigatinib, a drug that has indicated promising effects for relapse free survival in molecularly-selected, high-risk patients with urothelial carcinoma (UC) who have received radical surgery. Patients will receive Pemigatinib at a once-daily dose on a continuous schedule, continued until 12 months.

Conditions

Urothelial Cancer

Keywords

Urothelial carcinoma; FGFR inhibitor; Pemigatinib

Outcome Measures

Primary Outcomes (1)

• Mean Relapse-free Survival (RFS) After Start of Treatment With Pemigatinib.

  In the protocol, RFS at Year 2 was defined as the time from the start of treatment until disease relapse by Investigator determination, study-end or lost to follow-up, or death due to any cause. Due to the Covid-19 crisis causing significant delay of recruitment and the fact that we needed much more patients to identify patients with FGFR3 alterations, the study recruitment was prematurely stopped in November 2021 when 46 patients were screened and only 4 among 42 tested (9.5%) patients were identified with FGFR3 alterations. Two of the FGFR3 positive patients started treatment and the others were ineligible for the study. Since patients withdrawing from the study before completing the study period of 2 years cannot be included in the calculation of the 2-year RFS rate, the outcome results through premature study-end are presented.

  Mean Relapse-free survival rate from start of treatment through premature study-end with a maximal follow-up of 62 weeks.

Secondary Outcomes (1)

• Mean Overall Survival After Start of Treatment With Pemigatinib.

  Mean Overall Sturvival from start of treatment through premature study-end with a maximal follow-up of 62 weeks.

Study Arms (1)

Treatment arm

EXPERIMENTAL

Treatment with Pemigatinib at the protocol-defined dose administered orally once daily as continuous therapy schedule until 12 months.

Drug: Pemigatinib

Interventions

Pemigatinib DRUG

At Day 1, prior to the start of treatment, results from screening visit evaluations are reviewed to determine eligibility requirements. Subsequent visits during treatment phase will take place at Day 8, Day 15 and Day 21 and subsequently at 3 week intervals. Timing of subsequent visits can be prolonged to max. 9 week intervals if no problems exist during the first 12 weeks of therapy. Subjects will self-administer study drug using an oral QD regimen in a continuous dosing schedule. Each dose of Pemigatinib should be taken first thing in the morning upon waking or after a 2-hour fast; subjects should then fast for an additional 1 hour after taking study drug. The starting dose is 13.5 mg Pemigatinib. Study treatment will continue until 12 months, or until the evidence of disease relapse or onset of unacceptable toxicity.

Also known as: INCB054828

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological evidence of pT3-4 and/or pN1-3 UC of the urinary bladder or upper urinary tract after radical cystectomy / radical nephroureterectomy. Patients with mixed histologies are required to have a dominant (i.e. at least 50%) urothelial cell carcinoma pattern.
• Previous administration of at least 3 cycles of neoadjuvant cisplatin-based chemotherapy OR, if neoadjuvant chemotherapy was not administered, ineligibility to receive cisplatin-based adjuvant chemotherapy based on Galsky's criteria, that include at least one of the following: (1) WHO performance status ≥ 2 and/or (2) creatinine-clearance \< 60 ml/min and/or (3) CTCAE Gr ≥ 2 hearing loss and/or (4) CTCAE Gr ≥ 2 neuropathy.
• Evidence of FGFR alterations (mutations or translocations as specified in protocol) as assessed by a centralized Foundation Medicine test (Foundation One).
• Recovered with no evidence of disease confirmed by radiological images, prior to start of adjuvant therapy within 13 weeks after radical surgery.
• Willingness to avoid pregnancy or fathering children
• Written informed consent.

You may not qualify if:

• Any previous receipt of a selective FGFR inhibitor.
• Presence of primary CIS only.
• Presence of another malignancy in the 3 years before enrolment except for basal cell carcinoma or squamous cell carcinoma of the skin, cis of cervix, localised prostate cancer in active surveillance or other non invasive or other indolent malignancy that has undergone potentially curative therapy.
• Presence of pregnancy or lactation.
• Distant metastases (M1 disease).
• Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives (whichever is longer) before the first dose of study treatment.
• Abnormal laboratory parameters:
• Total bilirubin ≥ 1.5 × upper limit of normal (ULN; ≥ 2.5 × ULN if Gilbert syndrome).
• AST and/or ALT \> 2.5 × ULN
• Creatinine clearance ≤ 30 mL/min based on Cockroft-Gault.
• Serum phosphate \> institutional ULN.
• 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.
• History of human immunodeficiency virus infection or active tuberculosis infection.
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (exceeding \> 10 mg daily of prednison equivalent; inhalation steroids are permitted).
• Evidence of hepatitis B virus or hepatitis C virus active infection or risk of reactivation.

Sponsors & Collaborators

• European Association of Urology Research Foundation: lead
• Incyte Biosciences International Sàrl: collaborator
• AMS Advanced Medical Services GmbH: collaborator
• High Research s.r.l.: collaborator

Study Sites (5)

ASST Papa Giovanni XXIII

Bergamo, Italy

Location

Policlinico Sant'Orsola-Malpighi - Azienda Ospedaliero-Univeristaria di Bologna

Bologna, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

IRCCS San Raffaele Hospital

Milan, Italy

Location

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Roma, Italy

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pemigatinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Limitations and Caveats

In 2020, we started in 5 Italian centers. We expected that 30% of the screened patients (pts) had FGFR3 alterations (F3). Due to the Covid-19 crisis (recruitment delay) and the fact that we needed more pts to identify F3, recruitment prematurely stopped in Nov. 2021 with 42 pts screened and only 4/42 tested identified with F3 (9%). Two out of 4 pts were ineligible and only 2 started treatment and were followed until Study-End in Nov. 2022 resulting in a limited follow-up of maximal 62 weeks.

Results Point of Contact

• Title: Dr. Wim Witjes
• Organization: EAU Research Foundation

w.witjes@uroweb.org

31263890677

Study Officials

• Andrea Necchi, Dr.

  IRCCS San Raffaele Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, single-arm

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 4, 2020
• Study Start: July 13, 2020
• Primary Completion: November 15, 2021
• Study Completion: November 15, 2022
• Last Updated: April 18, 2025
• Results First Posted: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5)