Pemigatinib for Bladder Cancer

No longer recruiting at 6 trial locations

Overseen By Rana Sullivan, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Chemotherapy, Immunotherapy, Monoclonal antibodies, others

Disqualifiers: Upper urinary tract cancer, High-grade urothelial carcinoma, Active second malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called Pemigatinib for individuals with non-muscle invasive bladder cancer (NMIBC) that recurs. Participants will take Pemigatinib for 4-6 weeks before undergoing the standard procedure to remove bladder tumors. The trial seeks individuals who have previously had low- or intermediate-risk NMIBC tumors and have experienced tumor recurrence during regular check-ups. This trial might be suitable for those meeting these criteria. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have recently received anti-cancer therapy, radiotherapy, or undergone major surgery, you may need to wait 4 weeks before starting the study drug.

Is there any evidence suggesting that Pemigatinib is likely to be safe for humans?

Research shows that patients usually tolerate pemigatinib well. Studies have found that it has a good safety record, with most people not experiencing serious side effects. In past treatments for various cancers, pemigatinib was considered safe, and patients handled it well. This suggests that pemigatinib might be safe for individuals with non-muscle invasive bladder cancer, although individual experiences can differ. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Most treatments for bladder cancer involve surgery, chemotherapy, or immunotherapy. But pemigatinib works differently, targeting specific genetic alterations in cancer cells known as FGFR mutations. This precision approach means pemigatinib could potentially be more effective for patients whose tumors have these mutations, offering a personalized treatment plan. Researchers are excited because this targeted therapy could lead to better outcomes with fewer side effects compared to conventional treatments.

What evidence suggests that Pemigatinib might be an effective treatment for bladder cancer?

Research has shown that pemigatinib, the treatment under study in this trial, may help treat certain cancers. It targets specific proteins called fibroblast growth factor receptors (FGFRs), which can aid cancer cell growth. Studies have found pemigatinib effective in patients with FGFR changes, particularly in urothelial carcinoma, a type of bladder cancer. In these cases, pemigatinib was well tolerated and helped reduce or control the cancer. While most studies have focused on advanced cancer, the mechanism of pemigatinib suggests it might also benefit non-muscle invasive bladder cancer. Early results are promising, but more research is needed for this specific condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Noah M Hahn, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent non-muscle invasive bladder cancer that was previously low- or intermediate-risk. They must be able to perform daily activities with little to no assistance (ECOG status 0-2) and have certain lab values within specific ranges. People can't join if they've had recent radiotherapy, surgery, or other cancer treatments, have high-grade urothelial carcinoma in their latest urine test, another active cancer besides some exceptions, or previous treatment with similar drugs.

Inclusion Criteria

Your test results must be within certain ranges.

Patients who give a written informed consent obtained according to local guidelines

My bladder cancer is confirmed to be at a low or intermediate risk and has not invaded the muscle.

Exclusion Criteria

I received my last cancer treatment less than 4 weeks ago or am still experiencing side effects.

I haven't had major surgery or significant injury in the last 4 weeks, or minor procedures in the last week.

I have been treated with specific drugs targeting fibroblast growth factor receptors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pemigatinib for 4-6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT)

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of complete response rate and relapse-free survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Pemigatinib

Trial Overview The study tests Pemigatinib's effectiveness on patients with recurring bladder tumors who've had prior low- or intermediate-risk cancers. It's taken orally for 4-6 weeks before the standard tumor removal surgery (TURBT).

How Is the Trial Designed?

Group I: Treatment: Pemigatinib Experimental Treatment 1 Intervention

Patients will receive pemigatinib for 4 to 6 weeks prior to standard of care transurethral resection of bladder tumor (TURBT).

Pemigatinib is already approved in United States for the following indications:

Approved in United States as Pemazyre for:

• Unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement
• Relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

In a phase II study involving 260 patients with unresectable or metastatic urothelial carcinoma (UC) and FGFR3 alterations, pemigatinib showed clinical activity with overall response rates of 17.8% and 23.3% for different dosing schedules.

Pemigatinib was generally well tolerated, with common side effects including diarrhea and alopecia, and it demonstrated a median duration of response of about 6.2 months, indicating its potential as a treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemigatinib for Metastatic or Surgically Unresectable Urothelial Carcinoma With FGF/FGFR Genomic Alterations: Final Results From FIGHT-201. Necchi, A., Pouessel, D., Leibowitz, R., et al.[2023]

In a Phase 1 safety study involving six patients with non-muscle-invasive bladder cancer (NMIBC), intravesical administration of pembrolizumab was well tolerated, with no dose-limiting toxicities observed during dose escalation.

The treatment resulted in low-grade adverse events such as dysuria and fatigue, and importantly, there was no evidence of systemic absorption or immune effects, suggesting a localized action of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer. Woodcock, VK., Chen, JL., Purshouse, K., et al.[2023]

Pemigatinib, an FGFR tyrosine kinase inhibitor, effectively reduces cancer cell proliferation and induces apoptosis in lung, bladder, and gastric cancer cell lines by triggering G1 phase cell cycle arrest and increasing reactive oxygen species (ROS) production.

The treatment with pemigatinib also upregulates tumor suppressor microRNAs and downregulates oncogenic proteins, suggesting its potential as a therapeutic agent in combination with immunotherapy for cancers with FGFR alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting FGFRs by pemigatinib induces G1 phase cell cycle arrest, cellular stress and upregulation of tumor suppressor microRNAs. Pace, A., Scirocchi, F., Napoletano, C., et al.[2023]

Pembrolizumab, a checkpoint inhibitor, has been shown to significantly improve overall survival in patients with locally advanced or metastatic urothelial carcinoma who have progressed after cisplatin-containing chemotherapy, compared to standard chemotherapy options.

Additionally, evidence from Phase 1 and 2 trials suggests that checkpoint inhibitors like pembrolizumab are effective as a first-line treatment for patients who cannot tolerate cisplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of bladder cancer. Sundahl, N., Rottey, S., De Maeseneer, D., et al.[2018]

Pemigatinib is an effective treatment for patients with advanced cholangiocarcinoma that have FGFR2 genomic alterations, showing a 35.5% objective response rate after a median follow-up of 17.8 months in a phase II study.

The drug has a manageable safety profile, with common side effects including changes in blood phosphate levels, fatigue, and gastrointestinal issues, leading to its accelerated approval by the FDA for specific cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A drug safety evaluation of pemigatinib for advanced cholangiocarcinoma. Uson, PLS., Bearss, J., Babiker, HM., et al.[2023]

Pembrolizumab, an immunotherapy for advanced bladder cancer, led to significant tumor shrinkage after just one injection, demonstrating its efficacy in treating this type of cancer.

The patient experienced immune-related adverse events, specifically myasthenia gravis and myocarditis, which were effectively managed with early corticosteroid treatment, highlighting the importance of monitoring and addressing side effects in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced myasthenia gravis with myositis and presumable myocarditis in a patient with bladder cancer. Todo, M., Kaneko, G., Shirotake, S., et al.[2022]

In a phase I trial involving 12 Chinese patients with advanced solid tumors, pemigatinib showed acceptable safety and tolerability, with 25% of patients experiencing grade 3 or higher adverse events.

The drug demonstrated preliminary efficacy, with partial responses observed in two patients with specific FGFR mutations, indicating its potential as a targeted therapy for tumors with FGF/FGFR alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and efficacy of pemigatinib (a selective inhibitor of fibroblast growth factor receptor 1-3) monotherapy in Chinese patients with advanced solid tumors: a phase i clinical trial. Deng, T., Zhang, L., Shi, Y., et al.[2023]

The cuproptosis-associated 11 gene signature (CuAGS-11) model can effectively predict overall survival (OS) and progression-free survival (PFS) in bladder cancer patients, helping to stratify them into high- and low-risk groups based on their response to treatments like Bacillus Calmette-Guerin (BCG) and immune checkpoint inhibitors (ICIs).

Patients in the high-risk group showed significantly lower response rates to BCG and higher recurrence rates, while those in the low-risk group experienced much better outcomes, suggesting that the CuAGS-11 model can guide personalized treatment strategies and potentially reduce the need for invasive monitoring procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cuproptosis-associated 11 gene signature as a predictor for outcomes and response to Bacillus Calmette-Guerin and immune checkpoint inhibitor therapies in bladder carcinoma. Yuan, H., Xiu, Y., Liu, T., et al.[2023]

The combination of intravesical Bacillus Calmette-Guérin (BCG) and systemic pembrolizumab was found to be safe in a phase I trial involving 18 patients with high-grade non-muscle-invasive bladder cancer, with 69% of treated patients showing no evidence of disease after 3 months.

Despite some treatment-related adverse events, including one severe case of adrenal insufficiency and several grade 3 adverse events, the overall safety profile supports further investigation, leading to the initiation of a phase III trial to evaluate the efficacy of this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment. Alanee, S., Sana, S., El-Zawahry, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02872714

NCT02872714 | A Study to Evaluate the Efficacy and ... The purpose of this study is to evaluate the overall response rate (ORR) of pemigatinib as a monotherapy in the treatment of metastatic or surgically ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)05064-0/fulltext

Pemigatinib for metastatic or surgically unresectable ... In this analysis of final data from FIGHT-201, pemigatinib demonstrated clinical activity and manageable AEs in patients with previously treated ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37956738/

Pemigatinib for metastatic or surgically unresectable ... Pemigatinib was generally well tolerated and demonstrated clinical activity in previously treated, unresectable or metastatic UC with FGFR3 mutations or ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0923753423050640

Pemigatinib for metastatic or surgically unresectable ... Pemigatinib was generally well tolerated and demonstrated clinical activity in previously treated, unresectable or metastatic UC with FGFR3 mutations or ...

5. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-data-pemigatinib-its-selective-fgfr-inhibitor

Incyte Announces Data for Pemigatinib, its Selective FGFR ... Interim Phase 2 results highlight the potential of pemigatinib (INCB54828) in cholangiocarcinoma and urothelial carcinoma. WILMINGTON, Del.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03914794

NCT03914794 | A Study of Pemigatinib in Non-muscle ... Secondary endpoints will include safety profile, associations between complete response rate and tumor mutation/fusion status (e.g. FGFR3 specifically, others ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7313537/

INCB054828 (pemigatinib), a potent and selective inhibitor ... In phase 1 clinical trials, INCB054828 exhibited a favorable safety profile and target inhibition based on pharmacodynamic markers of FGFR ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03914794?term=NCT03914794&rank=1

A Study of Pemigatinib in Non-muscle Invasive Bladder ... Secondary endpoints will include safety profile, associations between complete response rate and tumor mutation/fusion status (e.g. FGFR3 specifically ...