Futibatinib + Pembrolizumab for Bladder Cancer

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

43 Participants Needed

Trial Summary

What is the purpose of this trial?

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 futibatinib and anti-programmed cell death-1 (PD-1) antibody pembrolizumab in patients with advanced or metastatic urothelial cancer who are not candidates to receive a platinum-based treatment regimens.

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.

What data supports the effectiveness of the drug combination Futibatinib and Pembrolizumab for bladder cancer?

Pembrolizumab has been shown to be effective in treating various forms of bladder cancer, including high-risk non-muscle-invasive bladder cancer and metastatic urothelial carcinoma, by improving survival rates and being well-tolerated compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of Futibatinib and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been studied for safety in various types of bladder cancer, including non-muscle-invasive and metastatic urothelial cancer. It has been generally well-tolerated in these studies, but like all medications, it can have side effects. There is no specific safety data available for the combination of Futibatinib and Pembrolizumab in the provided research. ^{1 2 3 6 7}

What makes the drug combination of Futibatinib and Pembrolizumab unique for bladder cancer?

This treatment combines Futibatinib, a drug that may target specific cancer cell pathways, with Pembrolizumab, an immune system booster that helps the body fight cancer cells. Pembrolizumab is already used for certain types of bladder cancer, but combining it with Futibatinib could offer a new approach for patients who have limited options. ^{1 2 3 4 8}

Eligibility Criteria

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 am 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and safety profile of pembrolizumab for metastatic urothelial cancer: A retrospective single-center analysis in Japan. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. [2018]

4. England 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. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab as Second-line Therapy for the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma in Sweden. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer. [2023]

7. England 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. [2022]

8. Australia 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. [2021]