Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements (FOENIX-CCA3)

A Phase 3, Open-Label, Randomized Study of Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements FOENIX-CCA3

This is an open-label, multinational, parallel 2-arm, randomized Phase 3 study evaluating the efficacy and safety of futibatinib versus gemcitabine-cisplatin chemotherapy as first-line treatment of patients with advanced, metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Cholangiocarcinoma; FGFR2 Gene Rearrangements
• Intervention / Treatment: Drug: TAS-120; Drug: Cisplatin/Gemcitabine

Detailed Description

Study TAS-120-301 is an open-label, multinational, parallel 2-arm, randomized Phase 3 study evaluating the efficacy and safety of futibatinib versus gemcitabine-cisplatin chemotherapy as first-line treatment of patients with advanced, metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements. Eligible patients will be randomized on a 1:1 basis to the following study arms:

• Experimental Arm: Patients will receive futibatinib at an oral dose of 20 mg, administered daily (QD) on every day of a 21-day cycle.

• Control Arm: On Days 1 and 8 of a 21-day cycle, patients will receive:

  • Cisplatin 25 mg/m2 in 1000 mL 0.9% saline by intravenous (I.V.) infusion over 1 hour, followed by 500 mL 0.9% saline over 30 minutes; and
  • Gemcitabine 1000 mg/m2 in 250-500 mL 0.9% saline by I.V. infusion over 30 minutes, beginning after completion of the cisplatin and saline infusions.

Patients in the Experimental Arm may continue to receive continuous futibatinib until documentation of progressive disease (PD) per RECIST 1.1, or until other withdrawal criteria are met, whichever comes first. However, treatment may continue following PD per RECIST 1.1 if the patient is clinically stable and is considered by the Investigator to be deriving continued clinical benefit from futibatinib.

Patients in the Control Arm may receive gemcitabine-cisplatin chemotherapy for up to 8 cycles or until PD or other withdrawal criteria are met, whichever comes first. Patients who discontinue gemcitabine-cisplatin due to documented disease progression (by ICR) may receive treatment with futibatinib ("crossover"), if medically appropriate in the opinion of the Investigator and if criteria for futibatinib treatment are met.

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Karim Benhadji, MD; Phone Number: 609-250-7336; Email: clinicaltrialinfo@taihooncology.com

Study Locations

• Argentina
  • Caba
    • Buenos Aires, Caba, Argentina, C1093
      • Fundación favaloro para la Docencia e Investigación Médica
    • Buenos Aires, Caba, Argentina, CP1264
      • Hospital de Gastroenterologia Dr. C. Bonorino Udaondo
• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • Newcastle Private Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Peter Maccallum Cancer Centre
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • UZ Antwerpen
    • Mechelen, Antwerpen, Belgium, 2800
      • Algemeen Ziekenhuis AZ Sint-Maarten
  • Flemish Region
    • Roeselare, Flemish Region, Belgium, 8800
      • AZ Delta Roeselare
  • Liege
    • Liège, Liege, Belgium, 4000
      • Chc Montlegia
• Brazil
  • PR
    • Curitiba, PR, Brazil, 80520-174
      • IOP - Instituto de Oncologia do Parana
  • RJ
    • Rio De Janeiro, RJ, Brazil, 20231-050
      • Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
    • Rio De Janeiro, RJ, Brazil, 22775-001
      • Instituto Americas
  • SP
    • Santo Andre, SP, Brazil, 09060-650
      • Cepho-Fm Abc
    • São José Do Rio Preto, SP, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
    • São Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo
    • São Paulo, SP, Brazil, 01509-010
      • Fundacao Antonio Prudente - A.C.Camargo Cancer Center
    • São Paulo, SP, Brazil, 04377-035
      • Hospital Municipal Vila Santa Catarina
    • São Paulo, SP, Brazil, 08270-120
      • Hospital Santa Marcelina HSM
• France
  • Clichy, France, 92110
    • Hopitaux Universitaires Paris Nord Val de Seine - Hopital Beaujon
  • Dijon, France, 21000
    • Centre Georges-Francois Leclerc
  • La Tronche, France, 38700
    • Centre Hospitalier Universitaire de Grenoble
  • Lyon, France, 69008
    • Centre Leon Bérard
  • Montbéliard, France, 25 200
    • CHRU Besançon
  • Reims, France, 51092
    • CHU Reims
  • Strasbourg, France, 67033
    • Institut de Cancerologie Strasbourg Europe ICAENS
  • Tours, France, 37044
    • CHU DE TOURS - Hopital Trousseau
• Germany
  • Berlin, Germany, 13353
    • Charite - Universitaetsmedizin Berlin
  • Mainz, Germany, 55131
    • Universitaetsmedizin Mainz
  • Muenchen, Germany, Muenchen
    • Technische Universitaet Muenchen - Klinikum Rechts Der Isar
• Hong Kong
  • Hong Kong, Hong Kong, 2255-4249
    • The University of Hong Kong, Queen Mary Hospital
  • Shatin, Hong Kong
    • The Chinese University of Hong Kong Prince of Wales Hospital
• Italy
  • Candiolo, Italy
    • Candiolo Cancer Institute - FPO IRCCS
  • Lucca, Italy, 555041
    • Ospedale Versilia
  • Monserrato, Italy, 9042
    • AOU di Cagliari
  • Novara, Italy, 28100
    • Ospedale Maggiore della Carità di Novara
  • Parma, Italy, 43126
    • Servizio Sanitario Regionale Emilia-Romagna - Azienda Ospedaliero-Universitaria di Parma Ospedale Maggiore
  • Roma, Italy, 12800
    • Policlinico Uni. Campus Bio-Medico
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
  • Verona, Italy, 37134
    • AOUI Verona - Ospedale Borgo Roma
  • Vicenza, Italy, 36100
    • Azienda ULSS 8 Berica
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Chiba
    • Chiba-shi, Chiba, Japan, 260-8677
      • Chiba University Hospital
    • Kashiwa-Shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Kanagawa
    • Yokohama-Shi, Kanagawa, Japan, 241-8515
      • Kanagawa cancer center
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 852-8501
      • Nagasaki University Hospital
  • Osaka
    • Osaka-shi, Osaka, Japan, 545-8586
      • Osaka City University Hospital
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Koto-Ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of JFCR
    • Mitaka-shi, Tokyo, Japan, 181-8611
      • Kyorin University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
  • Seongnam, Korea, Republic of, 13496
    • CHA Bundang Medical Center
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 3722
    • Yonsei University Health System - Severance Hospital
  • Jeollanam-Do
    • Hwasun, Jeollanam-Do, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital
  • Seoul
    • Jungni I Gu, Seoul, Korea, Republic of, 3080
      • Seoul National University Hospital
    • Seul, Seoul, Korea, Republic of, 5505
      • Asan Medical Center
• Mexico
  • Chiapas
    • Tuxtla Gutiérrez, Chiapas, Mexico, 29038
      • Centro de Estudios y Prevención del Cáncer (CEPREC)
  • MX
    • Mexico City, MX, Mexico, 14080
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario Jose Eleuterio Gonzalez
• Netherlands
  • GA
    • Nijmegen, GA, Netherlands, 6525
      • Radboud University Medical Center
• Peru
  • Arequipa, Peru, 04001
    • Hospital Goyeneche
  • Lima, Peru, 15082
    • Hospital Nacional Arzobispo Loayza
  • Callao
    • Bellavista, Callao, Peru, 07016
      • Hospital Daniel Alcides Carrion
  • Lima
    • Surquillo, Lima, Peru, 15038
      • Instituto Nacional de Enfermedades Neoplasicas (INEN)
• Poland
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 61-485
      • Centrum Medyczne HCP Sp. z o.o.
  • Woj. Wielkopolskie
    • Poznań, Woj. Wielkopolskie, Poland, 60-569
      • Szpital Kliniczny Przemienienia Pańskiego UM im. Karola Marcinkowskiego w Poznaniu
• Portugal
  • Lisboa, Portugal, 1400-038
    • Fundação Champalimaud
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia do Porto
  • Porto, Portugal, 4100-180
    • CUF Porto Hospital
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center
  • Madrid, Spain, 28022
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28043
    • Hospital Universitario 12 de Octubre
  • Pamplona, Spain
    • Clinica Universidad de Navarra
  • Gipuzkoa
    • Donostia-San Sebastian, Gipuzkoa, Spain, 20014
      • Onkologikoa
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Universitario Virgen de la Arrixaca HUVA
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Chang Gung Memorial Hospital Cgmh - Kaohsiung Branch
  • Taichung, Taiwan, 40447
    • Chang Gung Memorial Hospital, Linkou
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital Nckuh
  • Tainan, Taiwan, 710
    • Chi Mei Medical Center CMMC - Yongkang branch
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital
  • Bangkok, Thailand, 10210
    • Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy
  • ChiangMai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University
  • Muang
    • Khon Kaen, Muang, Thailand, 40002
      • Khon Kaen University KKU - Faculty of Medicine-Srinagarind Hospital
  • Songkhla
    • Hat Yai, Songkhla, Thailand, 90110
      • Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • University Hospitals Bristol NHS Foundation Trust
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, NW1 2PG
    • University College London Hospital NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Norton Cancer Institute Audubon Hospital Campus Medical Plaza
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • New Mexico Cancer Care Alliance
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates, PS - Summit Cancer Centers
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Carbone Comprehensive Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin - Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study:

1. Provide written informed consent.
2. Is ≥18 years of age (or meets the country's regulatory definition for legal adult age).
3. The patient has histologically confirmed, locally advanced, or metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements based on testing performed by the designated central laboratory.
4. Patient has radiographically measurable disease per RECIST 1.1.
5. Patients who have received treatment for locally advanced disease (for example, trans-arterial chemoembolization, selective internal radiation therapy, external beam radiation) must have evidence of radiographic progression with measurable disease outside the previously-treated lesions.
6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.

7. Adequate organ function as defined by the following criteria:

   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 ×upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT ≤ 5 × ULN.
   • Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert's syndrome.
   • White Blood Count (WBC) ≥ 2000/mm3 (≥ 2.0 × 109/L)
   • Absolute neutrophil count (ANC) ≥ 1000/mm3 (ie, ≥ 1.0 × 109/L by International Units [IU])
   • Platelet count ≥ 100,000/mm3 (IU: ≥ 100 × 109/L)
   • Hemoglobin ≥ 9.0 g/dL
   • Phosphorus ≤ 1.5 × ULN
   • Creatinine clearance: ≥ 60 mL/min
8. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of the first dose of futibatinib. Female patients are not considered to be of child bearing potential if they have a history of hysterectomy or are post menopausal defined as no menses for 12 months without an alternative medical cause. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose and for 6 months after the last dose.
9. Willing and able to comply with scheduled visits and study procedures.

Exclusion Criteria:

A patient will be excluded from this study if any of the following criteria are met:

1. Patient has received previous systemic anticancer therapy.

   • Patients receiving adjuvant or neoadjuvant treatment and completed ≥6 months prior to randomization are eligible.

2. Patient has mixed hepatocellular carcinoma - iCCA disease.

3. History and/or current evidence of any of the following disorders:

   • Non-tumor related alteration of calcium-phosphorus homeostasis that is clinically significant in the opinion of the Investigator.
   • Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator.
   • Retinal disorder confirmed by retinal examination and considered clinically significant in the opinion of the ophthalmologist.
4. History or current evidence of uncontrolled ventricular arrhythmias
5. Fridericia's corrected QT interval (QTcF) > 470 ms on electrocardiogram (ECG) conducted during Screening.

6. Treatment with any of the following within the specified time frame prior to the first dose of study therapy, or failure to recover from side effects of these prior therapies:

   • Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of study therapy).
   • Radiotherapy (any dose) for extended field within 4 weeks or limited field radiotherapy within 2 weeks, and/or has not recovered from acute impact of radiotherapy.
   • Patients with locoregional therapy, e.g. transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks.
   • Any history of liver transplant.

7. A serious illness or medical condition(s) including, but not limited to, the following:

   • Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month).
   • Known acute systemic infection.
   • Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the previous 6 months.
   • Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the Investigator.
   • Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death.
   • 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.
8. Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention.
9. Pregnant or breast-feeding female.
10. The patient is unable to take oral medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAS-120; TAS-120 tablets, oral; 21-day cycle	Drug: TAS-120; TAS-120 is an oral FGFR inhibitor; Other Names: Futibatinib
Active Comparator: Cisplatin/Gemcitabine; • On Days 1 and 8 of a 21-day cycle, patients will receive: Cisplatin 25 mg/m2 in 1000 mL 0.9% saline by intravenous (I.V.) infusion over 1 hour, followed by 500 mL 0.9% saline over 30 minutes; and; Gemcitabine 1000 mg/m2 in 250-500 mL 0.9% saline by I.V. infusion over 30 minutes, beginning after completion of the cisplatin and saline infusions.	Drug: Cisplatin/Gemcitabine; Cisplatin/Gemcitabine is currently 1st line standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS: defined as the time from date of randomization to the date of documentation of disease progression by ICR per RECIST (version 1.1, 2009) or date of death, whichever comes first.	Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per RECIST 1.1), based on ICR.	up to12 months
DCR	defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per RECIST 1.1), based on ICR.	up to 12 months
OS	defined as the time from the date of randomization until the date of death due to any cause.	up to 12 months
PFS per Investigator assessment	defined as the time from date of randomization to the date of disease progression based on Investigator assessment of radiographic images or death, whichever occurs first	up to 12 months
Safety and Tolerability	Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs)	up to 12 months

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: September 16, 2019
• First Submitted That Met QC Criteria: September 16, 2019
• First Posted (Actual): September 18, 2019

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Fusion; FGFR2; Futibatinib; Advanced Cholangiocarcinoma; Rearrangement; TAS-120
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Futibatinib; Gemcitabine
• Other Study ID Numbers: TAS-120-301; 2019-004630-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No