Urothelial CancerPhase 2PEGASUSNCT04294277
Safety and Efficacy of Pemigatinib in Patients With High-risk Urothelial Cancer After Radical Surgery
A Phase 2 study testing Pemigatinib in people with Urothelial Cancer, run by European Association of Urology Research Foundation at 5 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Cancer
- What is being tested?
- Pemigatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 5 sitesItaly
- Study dates
- 13 Jul 2020to 15 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
- Treatment with other investigational drugs, receipt of anticancer medications (except for neoadjuvant cisplatin-based chemotherapy, see second inclusion criterion) or radiotherapy after radical surgery.
Show all 21Show fewer
- 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.
- Severe hepatic impairment
- Known prior severe hypersensitivity to investigational products or its excipients
- History of clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of enrolment, New York Heart Association Class III or IV.
- Current evidence of corneal disorder/keratopathy (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc) or retinal disorder (including but not limited to, central serous retinopathy, macular/retinal degeneration, diabetic retino-pathy, retinal detachment, etc) as confirmed by ophthalmologic examination.
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Italy5 sites
ASST Papa Giovanni XXIII
Bergamo
Policlinico Sant'Orsola-Malpighi - Azienda Ospedaliero-Univeristaria di Bologna
Bologna
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
IRCCS San Raffaele Hospital
Milan
Fondazione Policlinico Universitario A. Gemelli, IRCCS
Roma
About this study
Official title: Open-label, Single-arm, Phase II Study, Evaluating Safety and Efficacy of INCB054828 (Pemigatinib) as Adjuvant Therapy for Molecularly-selected, High-risk Patients With Urothelial Carcinoma Who Have Received Radical Surgery
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.
Read the detailed description
This is an open-label, single-arm, Phase II study, evaluating safety and efficacy of INCB054828 (Pemigatinib) as adjuvant therapy for molecularly-selected, high-risk patients with urothelial carcinoma (UC) who have received radical surgery. Patients will receive Pemigatinib at a once-daily (QD) dose of 13.5 mg on a continuous schedule. Treatment will be continued until 12 months, or until the evidence of disease relapse or onset of unacceptable toxicity.
Hyperphosphatemia can be managed with diet modification, phosphate binders, or dose modification. Since mineralization of the cornea and retinal changes consisting of serous retinal detachment have been reported in humans, ophthalmic exams are done at baseline and once every 12 weeks during treatment and should include a visual acuity test, slit-lamp examination and fundoscopy. Additional assessments (e.g. Orbital computerized tomography (CT) should be done if clinically relevant retinal findings are observed on ophthalmologic exams and in participants with reported visual adverse events (AEs) or change in visual acuity, if the events or changes are suspected to be of retinal origin.
- Conditions
- Urothelial Cancer
- Being tested
- Pemigatinib
- Keywords
- Urothelial carcinoma, FGFR inhibitor, Pemigatinib
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PemigatinibDrug
Also called INCB054828
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Treatment with Pemigatinib at the protocol-defined dose administered orally once daily as continuous therapy schedule until 12 months. Receives: Drug: Pemigatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 Survival of patients who started treatment with Pemigatinib is defined as the time from the start of treatment until the last date known alive, or death due to any cause through premature study-end.
Measured: Mean Overall Sturvival from start of treatment through premature study-end with a maximal follow-up of 62 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2020
- Study start13 Jul 2020
- Primary completion15 Nov 2021
- Study completion15 Nov 2022
Why it stopped: Screening success and patient recruitment was much lower than projected and a clinical/scientific interpretation will not be possible.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Urothelial CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label, single-arm
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Association of Urology Research Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Biosciences International Sàrl, AMS Advanced Medical Services GmbH, High Research s.r.l.
- Responsible party
- Sponsor
- Investigators
- Andrea Necchi, Dr., Principal investigator, IRCCS San Raffaele Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04294277
- Sponsor's protocol ID
- EAU RF 2018-02
- Acronym
- PEGASUS
- Status last verified
- Apr 2025
- First submitted
- 2 Mar 2020
- Last updated
- 18 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single-arm, Phase II Study, Evaluating Safety and Efficacy of INCB054828 (Pemigatinib) as Adjuvant Therapy for Molecularly-selected, High-risk Patients With Urothelial Carcinoma Who Have Received Radical Surgery
- ClinicalTrials.gov ID
- NCT04294277
- Acronym / sponsor ID
- PEGASUS / EAU RF 2018-02
- Conditions
- Urothelial Cancer
- Keywords
- Urothelial carcinoma, FGFR inhibitor, Pemigatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Screening success and patient recruitment was much lower than projected and a clinical/scientific interpretation will not be possible.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- European Association of Urology Research FoundationUniversity, hospital or other
- Collaborators
- Incyte Biosciences International Sàrl, AMS Advanced Medical Services GmbH, High Research s.r.l.
- Study start
- 13 Jul 2020 (actual)
- Primary completion
- 15 Nov 2021 (actual)
- Study completion
- 15 Nov 2022 (actual)
- First posted
- 4 Mar 2020 (actual)
- Results
- Posted 18 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an open-label, single-arm, Phase II study, evaluating safety and efficacy of INCB054828 (Pemigatinib) as adjuvant therapy for molecularly-selected, high-risk patients with urothelial carcinoma (UC) who have received radical surgery. Patients will receive Pemigatinib at a once-daily (QD) dose of 13.5 mg on a continuous schedule. Treatment will be continued until 12 months, or until the evidence of disease relapse or onset of unacceptable toxicity.
Hyperphosphatemia can be managed with diet modification, phosphate binders, or dose modification. Since mineralization of the cornea and retinal changes consisting of serous retinal detachment have been reported in humans, ophthalmic exams are done at baseline and once every 12 weeks during treatment and should include a visual acuity test, slit-lamp examination and fundoscopy. Additional assessments (e.g. Orbital computerized tomography (CT) should be done if clinically relevant retinal findings are observed on ophthalmologic exams and in participants with reported visual adverse events (AEs) or change in visual acuity, if the events or changes are suspected to be of retinal origin.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label, single-arm
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: PemigatinibTreatment with Pemigatinib at the protocol-defined dose administered orally once daily as continuous therapy schedule until 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PemigatinibAlso: INCB054828At 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. | Drug | Treatment arm |
Primary outcome
Mean Relapse-free Survival (RFS) After Start of Treatment With Pemigatinib.
Time frame: Mean Relapse-free survival rate from start of treatment through premature study-end with a maximal follow-up of 62 weeks.
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.
1 secondary outcome
Mean Overall Survival After Start of Treatment With Pemigatinib.
Time frame: Mean Overall Sturvival from start of treatment through premature study-end with a maximal follow-up of 62 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Necchi, Dr. principal investigator
IRCCS San Raffaele Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pemigatinib in people with Urothelial Cancer, run by European Association of Urology Research Foundation at 5 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Relapse-free Survival (RFS) After Start of Treatment With Pemigatinib. (time frame: Mean Relapse-free survival rate from start of treatment through premature study-end with a maximal follow-up of 62 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2025; AzTrials last refreshed its copy on 8 Nov 2026.