Futibatinib for Bile Duct Cancer

(FOENIX-CCA4 Trial)

Recruiting at 76 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called futibatinib (Lytgobi) to evaluate its safety and effectiveness in treating bile duct cancer, specifically cholangiocarcinoma (CCA), with certain FGFR2 gene changes. Researchers aim to determine if different doses can benefit those whose cancer has progressed after treatments with gemcitabine and platinum-based drugs. Suitable candidates for this trial have CCA that cannot be surgically removed, show evidence of FGFR2 gene changes, and have experienced cancer progression despite treatment. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to explore new treatment options.

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.

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

Research has shown that futibatinib maintains a consistent and manageable safety record across various studies. A large safety review of 469 patients found that most side effects were temporary and reversible. However, another study reported serious side effects in about 39% of patients, including fever and digestive system bleeding, though these were rare. The FDA has approved futibatinib, also known as LYTGOBI, for patients with advanced conditions, indicating confidence in its safety for certain groups. Overall, while serious side effects can occur, they appear relatively rare and manageable. ^{1 2 3 4 5}

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

Futibatinib is unique because it targets the FGFR2 protein, a specific pathway involved in bile duct cancer growth. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, futibatinib specifically hones in on cancerous cells with FGFR2 alterations. This targeted approach aims to reduce side effects and improve effectiveness, offering hope for patients with limited options. Researchers are excited because this precision medicine could lead to better outcomes and a new standard of care for bile duct cancer.

What evidence suggests that futibatinib might be an effective treatment for bile duct cancer?

Research has shown that futibatinib may help treat bile duct cancer, particularly in patients with specific changes in the FGFR2 gene. In studies, 42% of patients experienced at least a 30% reduction in tumor size. The drug also halted tumor growth or spread for an average of 9.7 months. This trial will evaluate futibatinib in two dosages: 20mg and 16mg, administered in separate treatment arms. These findings suggest that futibatinib could help manage advanced bile duct cancer, offering a period of stability for patients. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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 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]

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]

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 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]

Citations

1. lytgobi.com lytgobi.com/hcp/efficacy-and-safety/efficacy-results

LYTGOBI® (futibatinib) tablets Efficacy Results Serious adverse reactions occurred in 39% of patients receiving LYTGOBI, and in ≥2% of patients included pyrexia (3.9%), gastrointestinal hemorrhage (3.9%), ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206834

Futibatinib for FGFR2-Rearranged Intrahepatic ... We evaluated patient-reported outcomes as a secondary end point and found that quality of life was stable over 9.0 months of futibatinib ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38884254/

futibatinib for people with advanced bile duct cancer Tumors shrank by at least 30% in 42% of people. Futibatinib stopped tumors from growing/spreading for a median of 9.7 months. People who took ...

4. fda.gov fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-lytgobi

Drug Trials Snapshot: LYTGOBI The FDA approved LYTGOBI based on evidence from one clinical trial (NCT02052778) consisting of 103 patients with previously treated, locally advanced or ...

5. taihooncology.com taihooncology.com/us/news/2022-09_lytgobi_approval/

2022-09_Lytgobi_Approval LYTGOBI (pronounced “light-GOH-bee”) delivered an objective response rate of 42% and median duration of response of 9.7 months in the primary ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38329716/

Pooled Safety Analysis of 469 Patients Futibatinib showed a consistent and manageable safety profile across patients with various tumor types. AECIs were mostly reversible with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12365427/

Safety profiles of the new target therapies—pemigatinib ... The median PFS was 9.0 months, with a 6-month progression-free survival rate of 66% and a 12-month rate of 40%. These data indicate that ...