Futibatinib for Bile Duct Cancer

(FOENIX-CCA4 Trial)

Recruiting at 61 trial locations

Overseen By Taiho Oncology, INC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Taiho Oncology, Inc.

Must not be taking: Anticancer, Targeted, Immunotherapy, others

Disqualifiers: Calcium disorder, Retinal disorder, Brain metastasis, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Continuous until disease progression or withdrawal

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multinational, randomized Phase 2 study confirming the clinical benefit of 20 mg futibatinib and evaluating the safety and efficacy of 16 mg futibatinib in previously treated CCA harboring FGFR2 gene fusions and other rearrangements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have taken any non-investigational anticancer therapy within 3 weeks before starting futibatinib. Endocrine therapy for breast or prostate cancer is allowed.

What data supports the effectiveness of the drug Futibatinib for bile duct cancer?

Futibatinib has shown effectiveness in treating bile duct cancer with FGFR2 gene mutations, achieving a 42% response rate and an average response duration of 9.7 months in clinical trials. It is particularly effective for patients with specific genetic changes in their cancer. ^{1 2 3 4 5}

Is futibatinib safe for humans?

Futibatinib has been shown to have a manageable safety profile in clinical trials, with common side effects including nail problems, muscle pain, constipation, diarrhea, fatigue, dry mouth, hair loss, mouth sores, and stomach pain. Important risks include eye problems and high phosphate levels in the blood. It was generally well-tolerated even in patients with liver impairment. ^{2 3 5 6 7}

How is the drug Futibatinib unique for treating bile duct cancer?

Futibatinib is unique because it is an irreversible inhibitor that specifically targets fibroblast growth factor receptors (FGFR 1-4), which are often altered in bile duct cancer. This drug is particularly effective for patients with FGFR2 gene mutations, offering a new option for those with advanced or metastatic intrahepatic cholangiocarcinoma. ^{1 2 3 4 8}

Eligibility Criteria

This trial is for adults with advanced Cholangiocarcinoma (bile duct cancer) that has specific genetic changes called FGFR2 fusions or rearrangements. Participants must have tried at least one chemo treatment before, show signs of cancer progression after the last treatment, and be in good physical condition with proper organ function.

Inclusion Criteria

My cancer is a type of bile duct cancer that cannot be surgically removed.

My cancer has a specific genetic change in the FGFR2 gene.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have a serious eye condition affecting my retina.

I have had local cancer treatment in the last 4 weeks.

I haven't had major surgery or extensive radiotherapy in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive futibatinib at an oral dose of either 16 mg or 20 mg daily on a 21-day cycle

Continuous until disease progression or withdrawal

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 12 months after study completion

Treatment Details

Interventions

• Futibatinib

Trial Overview The study is testing two doses of a drug named Futibatinib (16 mg and 20 mg) to see how well they work and how safe they are for patients who've had previous treatments for bile duct cancer with certain genetic alterations.

Participant Groups

Group I: Treatment Arm B Experimental Treatment 1 Intervention

TAS-120 (16mg) tablets, oral; 21-day cycle

Group II: Treatment Arm A Experimental Treatment 1 Intervention

TAS-120 (20mg) tablets, oral; 21-day cycle

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

Findings from Research

Futibatinib is an irreversible FGFR1-4 inhibitor that shows promise in treating advanced cancers, particularly cholangiocarcinoma, with a 42% objective response rate in a pivotal phase II trial involving previously treated patients with FGFR2 fusions.

The drug has a manageable safety profile, with hyperphosphatemia being the most common side effect, which was well managed and did not lead to treatment discontinuation, indicating its potential for maintaining patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Futibatinib, an Irreversible FGFR1-4 Inhibitor for the Treatment of FGFR-Aberrant Tumors. Javle, M., King, G., Spencer, K., et al.[2023]

Futibatinib is an FDA-approved treatment for unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma with FGFR2 gene mutations, showing an overall response rate of 42% in phase 3 clinical trials.

Patients treated with futibatinib experienced a duration of response of approximately 9.7 months, indicating its potential effectiveness in managing this rare type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Futibatinib: A Potent and Irreversible Inhibitor of Fibroblast Growth Factor Receptors for Treatment of the Bile Duct Cancer. De, SK.[2023]

Futibatinib is an oral medication that irreversibly inhibits fibroblast growth factor receptors (FGFR1-4) and has been approved for treating adult patients with unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma with FGFR2 gene fusions or rearrangements.

The drug was officially approved in the USA on September 30, 2022, marking a significant milestone in its development for various cancers, including cholangiocarcinoma, breast cancer, and others.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Futibatinib: First Approval. Syed, YY.[2022]

In a phase 2 study involving 103 patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma, futibatinib demonstrated a 42% objective response rate, with a median response duration of 9.7 months, indicating significant antitumor activity.

Futibatinib was associated with manageable safety profiles, with common grade 3 adverse events including hyperphosphatemia and fatigue, but no treatment-related deaths, and quality of life was maintained throughout the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. Goyal, L., Meric-Bernstam, F., Hollebecque, A., et al.[2023]

Futibatinib, an irreversible FGFR1-4 inhibitor, showed an objective response rate of 13.7% in a phase I trial with 197 patients across various advanced solid tumors, particularly effective in FGFR2 fusion-positive intrahepatic cholangiocarcinoma with a response rate of 25.4%.

The treatment had a manageable safety profile, with common side effects including hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%), supporting its further evaluation in ongoing phase II/III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study. Meric-Bernstam, F., Bahleda, R., Hierro, C., et al.[2023]

Futibatinib received accelerated FDA approval for treating unresectable intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions, showing an overall response rate of 42% and a median duration of response of 9.7 months in a multicenter trial with previously treated patients.

Common side effects included nail toxicity, musculoskeletal pain, and ocular toxicity, highlighting the importance of monitoring for these adverse reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Futibatinib for Unresectable Advanced or Metastatic, Chemotherapy Refractory Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Other Rearrangements. Gandhy, SU., Casak, SJ., Mushti, SL., et al.[2023]

Futibatinib, an FGFR1-4 inhibitor approved for advanced intrahepatic cholangiocarcinoma, was found to be well-tolerated in patients with varying degrees of hepatic impairment, with only mild adverse events reported.

The pharmacokinetics of futibatinib showed only minor increases in plasma concentration in patients with hepatic impairment, indicating that dose adjustments are not necessary for patients with mild to severe liver issues when taking a daily dose of 20 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I, open-label, single-dose study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of futibatinib. Gao, L., Yamamiya, I., Pinti, M., et al.[2023]

Futibatinib, an FGFR inhibitor, demonstrated a robust response in a 50-year-old woman with metastatic cholangiocarcinoma for 23.6 months, even after she had previously been treated with pemigatinib, indicating its potential effectiveness in cases of resistance to other FGFR-targeted therapies.

The treatment was safely administered despite the patient's history of decompensated cirrhosis and significant cytopenias, highlighting futibatinib's safety profile in challenging clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust Response to Futibatinib in a Patient With Metastatic FGFR-Addicted Cholangiocarcinoma Previously Treated Using Pemigatinib. Rengan, AK., Denlinger, CS.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Futibatinib, an Irreversible FGFR1-4 Inhibitor for the Treatment of FGFR-Aberrant Tumors. [2023]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Futibatinib: A Potent and Irreversible Inhibitor of Fibroblast Growth Factor Receptors for Treatment of the Bile Duct Cancer. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Futibatinib: First Approval. [2022]

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

Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. [2023]

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

Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study. [2023]

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

FDA Approval Summary: Futibatinib for Unresectable Advanced or Metastatic, Chemotherapy Refractory Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Other Rearrangements. [2023]

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

A phase I, open-label, single-dose study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of futibatinib. [2023]

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

Robust Response to Futibatinib in a Patient With Metastatic FGFR-Addicted Cholangiocarcinoma Previously Treated Using Pemigatinib. [2023]