Phase 2 Evaluation of Futibatinib in Advanced Cholangiocarcinoma with FGFR2 Fusions or Rearrangements

Trial ID: 2023-503665-39-00
Protocol: TAS-120-205
Sponsor: Taiho Oncology Inc.

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Diseases & Conditions

Cholangiocarcinoma

Objectives

The primary objective of this Phase 2 study is to assess the **efficacy** of **futibatinib** administered at 20 mg and 16 mg once daily (QD) in patients with advanced **cholangiocarcinoma** characterized by FGFR2 fusions or rearrangements. This evaluation aims to verify and describe the clinical benefit of futibatinib, which is crucial for determining its potential as a therapeutic option for this patient population.

Secondary objectives include:

Evaluating further efficacy parameters of futibatinib at the specified doses.
Assessing the **safety** and **tolerability** of the treatment regimen.
Evaluating Patient Reported Outcomes (PROs) to gain insights into the patient's perspective on the treatment's impact.

Participants

The clinical trial involves a total of **89 participants** diagnosed with **advanced cholangiocarcinoma**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific inclusion criteria, including histologically or cytologically confirmed locally advanced, metastatic, or unresectable intrahepatic or extrahepatic cholangiocarcinoma, documented evidence of FGFR2 gene fusions or rearrangements, and prior treatment with systemic gemcitabine and platinum-based regimens. The trial population also includes individuals with a measurable disease as defined by RECIST guidelines and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating a relatively good general health status. The study does not specify particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring comprehensive representation within the study cohort.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy of **futibatinib**, administered at doses of 20 mg and 16 mg, in patients with advanced **cholangiocarcinoma** characterized by FGFR2 fusions or rearrangements. This is a Phase II, randomized, double-blind, controlled study. The trial is expected to commence on June 1, 2023, and conclude by September 28, 2027. Participants will be involved in the study for a maximum treatment period of 21 days, with the possibility of early termination if specific conditions arise, such as adverse events or lack of compliance with the study protocol.

The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as histologically or cytologically confirmed advanced cholangiocarcinoma, documented FGFR2 gene fusions, and measurable disease as per RECIST guidelines. Follow-up visits will be scheduled to monitor the participants' response to the treatment, assess safety, and document any adverse events. The end-of-study visit will evaluate the overall response rate (ORR) and other secondary endpoints, including duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

Participants will be required to adhere to the study protocol, which includes oral administration of the investigational product, **futibatinib**, in the form of film-coated tablets. The primary endpoint is the ORR by independent central review, defined as the proportion of patients experiencing a partial or complete response. Secondary endpoints include DoR, PFS, OS, and safety assessments based on adverse events, clinical laboratory parameters, and vital signs. The study will also evaluate patient-reported outcomes (PROs) using the EORTC QLQ-C30 and EQ-5D instruments. Conditions that may lead to early termination from the study include significant adverse events, non-compliance, or withdrawal of consent by the participant.

Treatment

The clinical trial involves the administration of **Futibatinib**, a chemical compound developed by Taiho Oncology, Inc. The experimental medication is provided in the form of a **film-coated tablet**. The active substance, **futibatinib**, is administered orally. The dosing regimen includes a maximum daily dose of 20 mg, with a total maximum dose of 420 mg over a treatment period of 21 days. The trial aims to evaluate the efficacy of futibatinib at dosages of 20 mg and 16 mg once daily (QD) in patients with advanced **cholangiocarcinoma** characterized by FGFR2 fusions or rearrangements. The medication is not formulated for pediatric use and has been designated as an orphan drug under the designation number EU/3/19/2146.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus remains solely on the administration of futibatinib to assess its clinical benefit. Participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen. The trial is conducted under the authorization number DE_BW_01_MIA_2023_0054, and the product is identified by the sponsor product code TAS-120. The pharmaceutical form and administration route are consistent with standard practices for oral medications, ensuring ease of administration and patient compliance.

Efficacy

The efficacy of **futibatinib** in patients with advanced cholangiocarcinoma with FGFR2 fusions or rearrangements will be assessed through a Phase 2 clinical trial. The primary endpoint for evaluating efficacy is the Objective Response Rate (ORR) by independent central review, defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1. Secondary endpoints include Duration of Response (DoR) and Progression-Free Survival (PFS) by blinded independent central review (BICR), as well as ORR, DoR, and PFS by investigator assessment. Overall Survival (OS) will also be measured.

Additional assessments will include safety evaluations based on adverse events (AEs), particularly those of Grade 3 or higher, serious adverse events (SAEs), dose modifications, clinical laboratory parameters, ophthalmological exams, and vital signs. Patient-reported outcomes (PROs) will be measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EuroQol-5D (EQ-5D) instruments. The trial is designed to verify and describe the clinical benefit of futibatinib administered at doses of 20 mg and 16 mg once daily (QD). The study is expected to conclude by September 28, 2027.

Inclusion and Exclusion Criteria

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Inclusion Criteria

A patient must meet all of the following inclusion criteria to be eligible for participation in this study: 1. Histologically or cytologically confirmed, locally advanced, metastatic, or unresectable intrahepatic of extrahepatic Cholangiocarcinoma.
Documented evidence of FGFR2 gene fusions or other FGFR2 rearrangement Received at least one prior systemic gemcitabine and platinum-based regimen for CCA
Documentation of radiographic disease progression on the most recent prior therapy Measurable disease performance status 0 or 1 Adequate organ function
Documentation of radiographic disease progression on the most recent prior therapy
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009)
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

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Exclusion Criteria

A patient must not meet any of the following exclusion criteria to be eligible for participation in this study: 1. History or current evidence of calcium and phosphate homeostasis disorder
Current evidence of clinically significant retinal disorder
Treatment with any of the following within the specified time frame prior to the first dose of futibatinib: a. Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of futibatinib) and radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks b. Patients with locoregional therapy, eg, transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks c. Any noninvestigational anticancer therapy within 3 weeks or have not recovered from side effects of such therapy prior to futibatinib administration. Endocrine therapy is allowed for patients with breast or prostate cancer d. Targeted therapy or immunotherapy within 3 weeks or within 5 half lives (whichever is shorter) e. Any investigational agent received within 5 half-lives of the drug or 4 weeks, whichever is shorter. g. Patients with prior FGFR-directed therapy
A serious illness or medical condition(s) including (but not limited to) the following: a. Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for ≥1 month b. Known acute systemic infection c. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV within the previous 2 months; if >2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms d. Significant gastrointestinal disorder(s) that could interfere with the absorption of futibatinib e. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the Investigator would make the patient inappropriate for entry into this study
Known additional malignancy that is progressing or requires active treatment, with the exception of patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or antitumor assessment of the investigational regimen. Exceptions must be discussed with the Sponsor prior to patient enrollment.
Pregnant or lactating female
Known hypersensitivity or severe reaction to futibatinib or its excipients.