Futibatinib for Bile Duct Cancer
(FOENIX-CCA4 Trial)
Recruiting in Palo Alto (17 mi)
+62 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Taiho Oncology, Inc.
Must not be taking: Anticancer, Targeted, Immunotherapy, others
Disqualifiers: Calcium disorder, Retinal disorder, Brain metastasis, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
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.
12345Is 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.
23567How 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.
12348Eligibility 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.
+4 more
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.
+12 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Treatment Arm BExperimental Treatment1 Intervention
TAS-120 (16mg) tablets, oral; 21-day cycle
Group II: Treatment Arm AExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Tampa General Hospital Cancer InstituteTampa, FL
Texas Onc Methodist (Charlton)Dallas, TX
Texas OncologyAbilene, TX
Center for Oncology and Blood DisordersHouston, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Taiho Oncology, Inc.Lead Sponsor
References
Futibatinib, an Irreversible FGFR1-4 Inhibitor for the Treatment of FGFR-Aberrant Tumors. [2023]Fibroblast growth factor receptors (FGFR) are emerging as an important therapeutic target for patients with advanced, refractory cancers. Most selective FGFR inhibitors under investigation show reversible binding, and their activity is limited by acquired drug resistance. This review summarizes the preclinical and clinical development of futibatinib, an irreversible FGFR1-4 inhibitor. Futibatinib stands out among FGFR inhibitors because of its covalent binding mechanism and low susceptibility to acquired resistance. Preclinical data indicated robust activity of futibatinib against acquired resistance mutations in the FGFR kinase domain. In early-phase studies, futibatinib showed activity in cholangiocarcinoma, and gastric, urothelial, breast, central nervous system, and head and neck cancers harboring various FGFR aberrations. Exploratory analyses indicated clinical benefit with futibatinib after prior FGFR inhibitor use. In a pivotal phase II trial, futibatinib demonstrated durable objective responses (42% objective response rate) and tolerability in previously treated patients with advanced intrahepatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements. A manageable safety profile was observed across studies, and patient quality of life was maintained with futibatinib treatment in patients with cholangiocarcinoma. Hyperphosphatemia, the most common adverse event with futibatinib, was well managed and did not lead to treatment discontinuation. These data show clinically meaningful benefit with futibatinib in FGFR2-rearrangement-positive cholangiocarcinoma and provide support for further investigation of futibatinib across other indications. Future directions for this agent include elucidating mechanisms of resistance and exploration of combination therapy approaches.
Futibatinib: A Potent and Irreversible Inhibitor of Fibroblast Growth Factor Receptors for Treatment of the Bile Duct Cancer. [2023]Cholangiocarcinoma is a rare type of cancer. Futibatinib is an irreversible, potent, selective inhibitor of fibroblast growth factor receptors (FGFR 1-4). On September 30, 2022, the US FDA first approved futibatinib to treat adult patients with bile duct cancer whose disease is unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene mutations or other classes of rearrangements. The approval of this medicine was based on phase 3 clinical trial results including an overall response rate (ORR) of 42% and a duration of response (DoR) of 9.7 months. This short perspective summarizes Futibatinib's synthesis, physicochemical properties, dosage, route of administration, mechanism of action, binding mode, pharmacodynamics, pharmacokinetics, drug interactions, adverse events, and possible mechanism of resistance.
Futibatinib: First Approval. [2022]Futibatinib (Lytgobi®) is an oral, covalently binding, irreversible inhibitor of fibroblast growth factor receptor (FGFR)1-4 that is being developed by Taiho Oncology and Taiho Pharmaceutical for the treatment of cancers, including cholangiocarcinoma, breast cancer, gastric cancer, urothelial cancer, oesophageal cancer and non-small cell lung cancer. Futibatinib was approved in the USA on 30 September 2022 for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harbouring FGFR2 gene fusions or other rearrangements. This article summarizes the milestones in the development of futibatinib leading to this first approval.
Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. [2023]Label="BACKGROUND">Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.
Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study. [2023]Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, was evaluated in a large multihistology phase I dose-expansion trial that enrolled 197 patients with advanced solid tumors. Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer) bearing both known and previously uncharacterized FGFR1-3 aberrations. The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients with acquired resistance to a prior FGFR inhibitor also experienced responses with futibatinib. Futibatinib demonstrated a manageable safety profile. The most common treatment-emergent adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy. SIGNIFICANCE: This phase I dose-expansion trial demonstrated clinical activity and tolerability of the irreversible FGFR1-4 inhibitor futibatinib across a broad spectrum of FGFR-aberrant tumors. These results formed the rationale for ongoing phase II/III futibatinib trials in cholangiocarcinoma, breast cancer, gastroesophageal cancer, and a genomically selected disease-agnostic population.This article is highlighted in the In This Issue feature, p. 275.
FDA Approval Summary: Futibatinib for Unresectable Advanced or Metastatic, Chemotherapy Refractory Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Other Rearrangements. [2023]On September 30, 2022, the FDA granted accelerated approval to futibatinib for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions or other rearrangements. Approval was based on Study TAS-120-101, a multicenter open-label, single-arm trial. Patients received futibatinib 20-mg orally once daily. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR) as determined by an independent review committee (IRC) according to RECIST v1.1. ORR was 42% (95% confidence interval, 32%-52%). Median DoR was 9.7 months. Adverse reactions occurring in ≥30% patients were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, and abdominal pain. The most common laboratory abnormalities (≥50%) were increased phosphate, increased creatinine, decreased hemoglobin, and increased glucose. Ocular toxicity (including dry eye, keratitis, and retinal epithelial detachment) and hyperphosphatemia are important risks of futibatinib, which are listed under Warnings and Precautions. This article summarizes the FDA's thought process and data supporting the approval of futibatinib.
A phase I, open-label, single-dose study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of futibatinib. [2023]Futibatinib is a covalently binding FGFR1-4 inhibitor that received US Food and Drug Administration approval for the treatment of patients with previously treated, advanced intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions/rearrangements. This phase I trial evaluated the pharmacokinetics (PKs), safety, and tolerability of futibatinib in subjects with impaired hepatic function and matched healthy volunteers. Twenty-two subjects with hepatic impairment (8 mild [Child-Pugh 5-6], 8 moderate [7-9], and 6 severe [10-15]) and 16 matched healthy control subjects received a single oral dose of futibatinib 20 mg. Futibatinib PKs were compared between subjects with mild/moderate/severe hepatic impairment and each corresponding control cohort and the overall control cohort. Relationships between futibatinib PKs and Child-Pugh scores and liver function tests were examined via scatter/regression plots. Compared with matched controls, the area under the plasma concentration-time curve from time zero to infinity increased by 21%/20%/18% and the maximum plasma concentration (Cmax ) increased by 43%/15%/10% in subjects with mild/moderate/severe hepatic impairment, respectively. Changes were not considered clinically relevant: geometric mean ratios were within 80%-125%, except for Cmax in subjects with mild hepatic impairment (143%). No obvious trends were observed among futibatinib PK parameters versus Child-Pugh scores, bilirubin, albumin, international normalized ratio, and aspartate aminotransferase (all p > 0.05). Futibatinib was well-tolerated, with only four grade 1 treatment-emergent adverse events (mild hepatic impairment = 2 and control = 2). The results demonstrate that futibatinib dose adjustments due to mild/moderate/severe hepatic impairment are not necessary in patients receiving futibatinib 20 mg daily.
Robust Response to Futibatinib in a Patient With Metastatic FGFR-Addicted Cholangiocarcinoma Previously Treated Using Pemigatinib. [2023]Futibatinib is a novel FGFR inhibitor currently under investigation as a second-line treatment for locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusions and rearrangements. As FGFR-targeted therapies move into the frontline setting, sequencing of these drugs remains undetermined. To date, no study has investigated the use of futibatinib in the context of pemigatinib resistance. We describe a 50-year-old woman with metastatic FGFR-aberrant intrahepatic cholangiocarcinoma who showed a robust response to futibatinib for 23.6 months, having previously benefited from pemigatinib. Futibatinib was safely used despite her history of decompensated cirrhosis and significant cytopenias. We observed a reduction in CA 19-9 level and a partial radiographic response on futibatinib. Serial next-generation sequencing and cell-free DNA testing proved crucial to making appropriate treatment decisions.