Futibatinib + Pembrolizumab for Bladder Cancer

Not currently recruiting at 18 trial locations

Overseen By Taiho Oncology, INC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Taiho Oncology, Inc.

Must not be taking: Anti-PD-1, FGFR inhibitors

Disqualifiers: Autoimmune disease, Pneumonitis, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two treatments: futibatinib (a targeted therapy) and pembrolizumab (an immunotherapy). The goal is to evaluate their effectiveness against bladder cancer that has spread or cannot be treated with standard chemotherapy. The trial targets patients with specific genetic changes in their cancer cells, such as FGFR mutations, and those ineligible for platinum-based treatments. It suits individuals with advanced or metastatic urothelial cancer who have not yet received treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of futibatinib and pembrolizumab is generally well-tolerated in patients unable to receive platinum-based treatments. Studies indicate that the most common side effects include high phosphate levels in the blood and diarrhea. High phosphate levels occurred in 54% of patients, but only 3 experienced it severely. Diarrhea affected 44% of patients, with 3 reporting it as severe. These findings suggest that while some side effects are common, they are often manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about futibatinib and pembrolizumab for bladder cancer because they target cancer in unique ways. Unlike current treatments that often include chemotherapy or immune checkpoint inhibitors alone, this combination pairs an FGFR inhibitor (futibatinib) with an immune checkpoint inhibitor (pembrolizumab). Futibatinib blocks specific growth signals in cancer cells with FGFR mutations, potentially halting their spread, while pembrolizumab enhances the body's immune response against the cancer. This dual-action approach might offer a new avenue for patients who have genetic variations that make their cancer resistant to other treatments.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that the combination of futibatinib and pembrolizumab, which participants in this trial will receive, has promising effects in patients with advanced or spreading bladder cancer. Previous studies found that this treatment led to lasting improvements, especially in patients with specific FGFR3 gene changes. About 30% of patients experienced tumor shrinkage, meaning nearly one-third saw positive results. The treatment was manageable, with no major side effects limiting the dose. These findings suggest this treatment could be effective for those who cannot undergo platinum-based therapies. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic urothelial carcinoma who can't have platinum-based chemo are eligible. They must be in good physical condition (ECOG PS 0-1), have proper organ function, and measurable disease. Cohort A requires an FGFR3 mutation or FGFR1-4 fusion; Cohort B includes all other patients. Exclusions include significant non-tumor related health issues, recent live vaccines, active autoimmune diseases requiring treatment within 2 years, certain infections like HIV/Hepatitis B/C, prior anti-PD-1/L1/L2 or FGFR inhibitor therapy.

Inclusion Criteria

I have urothelial cancer with any genetic background.

I cannot tolerate or am not suitable for standard platinum-based chemotherapy.

I can carry out all my usual activities without help.

Exclusion Criteria

I have been treated for an autoimmune disease in the last 2 years.

I have had pneumonitis treated with steroids or have it now.

I have HIV or a history of Hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive futibatinib and pembrolizumab to evaluate antitumor activity and confirm safety

Approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Futibatinib
• Pembrolizumab

Trial Overview The trial is testing the combination of futibatinib (an FGFR inhibitor) and pembrolizumab (a PD-1 antibody) for their effectiveness and safety in treating urothelial cancer when standard chemotherapy isn't suitable.

How Is the Trial Designed?

Group I: futibatinib and pembrolizumab (Cohort B) Experimental Treatment 1 Intervention

All other patients than in Cohort A with UC (including patients with other FGFR or non-FGFR genetic aberrations and patients with wild-type \[non-mutated\] tumors).

Group II: futibatinib and pembrolizumab (Cohort A) Experimental Treatment 1 Intervention

Patients with UC and FGFR3 mutation or FGFR1-4 fusion/rearrangement.

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

Approved in United States as Lytgobi for:

• Treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

In a study comparing 121 patients treated with pembrolizumab to 67 patients receiving conventional chemotherapy for advanced urothelial carcinoma, pembrolizumab showed a significant improvement in overall survival with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death compared to chemotherapy.

Despite the older age and poorer health status of patients receiving pembrolizumab, the treatment demonstrated a clinical benefit over traditional chemotherapy, suggesting its effectiveness as a second-line therapy in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of pembrolizumab with conventional chemotherapy after first-line platinum-based chemotherapy for advanced urothelial carcinoma in real-world practice: A multicenter retrospective study. Narita, T., Hatakeyama, S., Numakura, K., et al.[2021]

In a study of 74 Japanese patients with metastatic urothelial carcinoma treated with pembrolizumab, the objective response rate was 30.2%, with a median overall survival of 13.3 months, indicating its effectiveness as a second-line treatment.

The safety profile showed that over half of the patients experienced adverse events, with 10.9% suffering from severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety profile of pembrolizumab for metastatic urothelial cancer: A retrospective single-center analysis in Japan. Fujiwara, M., Yuasa, T., Urasaki, T., et al.[2022]

In a study involving 101 patients with BCG-unresponsive non-muscle-invasive bladder cancer, pembrolizumab showed a promising clinical complete response rate of 41% at 3 months, indicating its potential as an effective treatment option for patients who cannot undergo surgery.

The treatment was generally well-tolerated, with only 13% of patients experiencing grade 3 or 4 adverse events, suggesting that pembrolizumab is a safe alternative for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Balar, AV., Kamat, AM., Kulkarni, GS., et al.[2022]

In the Phase III KEYNOTE-045 trial, pembrolizumab significantly improved overall survival in patients with second-line metastatic urothelial carcinoma compared to standard treatments like docetaxel, paclitaxel, and vinflunine.

Early results from the Phase II KEYNOTE-052 trial suggest that pembrolizumab is effective for first-line treatment in patients with metastatic urothelial carcinoma who are not eligible for cisplatin, leading to its FDA approval for these indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. Lundgren, KT., Farina, MS., Bellmunt, J.[2018]

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]

In a study involving 33 patients with advanced urothelial cancer, pembrolizumab demonstrated anti-tumor activity, with a 26% overall response rate, including 11% complete responses and 15% partial responses, after a median follow-up of 13 months.

The treatment was found to have an acceptable safety profile, with common side effects including fatigue and peripheral edema, and no treatment-related deaths reported, supporting further investigation in larger phase 2 and 3 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study. Plimack, ER., Bellmunt, J., Gupta, S., et al.[2022]

Citations

1. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-bladder-cancer/154847-esmo-2024-phase-2-study-of-futibatinib-plus-pembrolizumab-in-patients-pts-with-advanced-metastatic-urothelial-carcinoma-muc-final-analysis-of-efficacy-and-safety.html

Phase 2 Study of Futibatinib plus Pembrolizumab in ... This phase 2 trial was designed to assess the efficacy and safety of the first-line combination of futibatinib and pembrolizumab in patients with metastatic ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03569-5/fulltext

1965MO Phase II study of futibatinib plus pembrolizumab ... Conclusions. Futibatinib plus pembrolizumab had encouraging antitumor activity with durable responses in pts with mUC, particularly among pts with FGFR3 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.501

Futibatinib plus pembrolizumab in patients (pts) with ... Conclusions: Preliminary safety results support tolerability of futibatinib plus pembrolizumab in platinum-ineligible pts with mUC. As no DLTs ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04601857

Study Details | NCT04601857 | Futibatinib and ... The purpose of the trial is to evaluate the antitumor activity and confirm the safety for the combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11557252/

FGFR Inhibitors in Urothelial Cancer - PubMed Central - NIH The FIERCE-22 trial and a study evaluating futibatinib with pembrolizumab demonstrated encouraging results, with an ORR of 30% and a safety ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04601857

Study Details | NCT04601857 | Futibatinib and ... The purpose of the trial is to evaluate the antitumor activity and confirm the safety for the combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor ...

7. bcan.org bcan.org/clinicaltrials/futibatinib-and-pembrolizumab-combination-in-the-treatment-of-advanced-or-metastatic-urothelial-carcinoma/

Futibatinib and Pembrolizumab Combination in the ... The purpose of the trial is to evaluate the antitumor activity and confirm the safety for the combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor ...