Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma (FIRST-308)

July 1, 2026 updated by: TransThera Sciences (Nanjing), Inc.

A Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib VS Physician's Choice in Subjects With FGFR-altered, Chemotherapy- and FGFR Inhibitor-Cholangiocarcinoma

This study is a Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib versus Physician's Choice in Subjects with Fibroblast Growth Factor Receptor (FGFR)-altered, Chemotherapy- and FGFR Inhibitor-Refractory/Relapsed Cholangiocarcinoma

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Approximately 200 subjects will be enrolled. Eligible subjects will be randomized in a 2:2:1 ratio to receive tinengotinib 8 mg QD, tinengotinib 10 mg QD or Physician's Choice in Part A; and eligible subjects will be randomized in a 2:1 ratio to receive the recommended Part B dose or selected dose or Physician's Choice in Part B.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Linz, Austria
        • Ordensklinikum Linz GmbH
      • Wiener Neustadt, Austria
        • Landesklinikum Wiener Neustadt
  • Belgium
      • Antwerp, Belgium
        • Universitair Ziekenhuis Antwerpen
      • Ghent, Belgium
        • Universitair Ziekenhuis Gent
      • Leuven, Belgium
        • Universitair Ziekenhuis Leuven
  • France
      • Avignon, France
        • Institut Sainte Catherine - Institut du Cancer Avignon Provence
      • Besançon, France
        • Centre Hospitalier Régional Universitaire de Besançon
      • Clichy, France
        • Hôpital Beaujon
      • Levallois-Perret, France
        • Hôpital Franco-Britannique - fondation Cognacq-Jay
      • Lyon, France
        • Clinique de la Sauvegarde
      • Montpellier, France
        • Centre Hospitalier Universitaire de Montpellier
      • Paris, France
        • Hôpital Saint Antoine
      • Villejuif, France
        • Institut de Cancérologie Gustave Roussy
  • Germany
      • Baden, Germany
        • Krebszentrum Reutlingen
      • Frankfurt, Germany
        • Krankenhaus Nordwest gGmbH
      • Hamburg, Germany
        • Asklepios Klinik Altona
      • Hanover, Germany
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany
        • Universitaetsklinikum Heidelberg (UKHD) - Nationales Centrum fuer Tumorerkrankungen Heidelberg (NCT)
      • München, Germany
        • Ludwig-Maximilians-Universität München Kum
  • Italy
      • Ancona, Italy
        • Clinica Oncologica, Ospedali Riuniti Umberto 1
      • Candiolo, Italy, 10060
        • Candiolo Cancer Institute - FPO IRCCS
      • Meldola, Italy
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Milan, Italy
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Milan, Italy
        • Istituto Europeo di Oncologia IRCCS
      • Milan, Italy
        • ASST Grande Ospedale Metropolitano Niguard
      • Naples, Italy
        • Istituto Nazionale Tumori Irccs Fondazione g. Pascale
      • Naples, Italy
        • Azienda Ospedaliera Universitaria Luigi Vanvitelli
      • Parma, Italy
        • Azienda Ospedaliera Universitaria di Parma
      • Pisa, Italy
        • Azienda Ospedaliero-Universitaria Pisana
      • Rozzano, Italy
        • Humanitas Research Hospital
      • Siena, Italy
        • Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
      • Verona, Italy
        • AOUI Verona - Ospedale Borgo Roma
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Amsterdam UMC, location AMC
  • Poland
      • Warsaw, Poland
        • Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie
  • Portugal
      • Lisbon, Portugal
        • Fundacao Champalimaud
      • Lisbon, Portugal
        • Centro Hospitalar Lisboa Norte CHLN EPE - Hospital de Santa Maria
  • South Korea
      • Busan, South Korea, 49201
        • Dong-A University Hospital
      • Busan, South Korea, 48108
        • Inje University Haeundae Paik Hospital
      • Daegu, South Korea, 41944
        • Kyungpook National University Hospital
      • Incheon, South Korea, 21565
        • Gachon University Gil Medical Center
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, South Korea, 06351
        • Samsung Medical Center
      • Seoul, South Korea, 03722
        • Yonsei University Health System - Severance Hospital
      • Seoul, South Korea, 08308
        • Korea University Guro Hospital
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, South Korea, 13496
        • CHA Bundang Medical Center
    • Gyeongsangnam-do
      • Jinju, Gyeongsangnam-do, South Korea, 52727
        • Gyeongsang National University Hospital
    • Jeollanam-do
      • Hwasun, Jeollanam-do, South Korea, 58128
        • Chonnam National University Hwasun Hospital
  • Spain
      • Barcelona, Spain
        • Hospital Clinic de Barcelona
      • Barcelona, Spain
        • Hospital Universitari Vall d´Hebron
      • Córdoba, Spain
        • Hospital Universitario Reina Sofa
      • Madrid, Spain
        • Hospital General Universitario Gregorio Marañon
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain
        • Clínica Universidad de Navarra
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain
        • HM Hospital Universitario Madrid Sanchinarro - CIOCC
      • Pamplona, Spain
        • Clínica Universidad de Navarra
      • Santiago de Compostela, Spain
        • Hospital Clínico Universitario de Santiago de Compostela
      • Zaragoza, Spain
        • Hospital Universitario Miguel Servet
  • Taiwan
      • Kaohsiung City, Taiwan, 80756
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Kaohsiung City, Taiwan, 833401
        • Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
  • United Kingdom
      • London, United Kingdom
        • Royal Marsden Hospital NHS
      • London, United Kingdom
        • UCG-1st floor central
      • Manchester, United Kingdom
        • The Christie NHS Foundation Trust - Christie Hospital
      • Nottingham, United Kingdom
        • Nottingham University Hospitals NHS Trust
  • United States
    • California
      • Santa Monica, California, United States, 90401
        • UCLA Medical Center
      • Stanford, California, United States, 94305
        • Stanford Cancer Center
      • Westwood, Los Angeles, California, United States, 90024
        • The University of Kansas Cancer Center
    • Florida
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Comprehensive Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60601
        • The University of Chicago Hospitals
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48103
        • University of Michigan
      • Detroit, Michigan, United States, 48201
        • Henry Ford
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota- Masonic Cancer Center, M Health Fairview
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Comprehensive Cancer Center
    • North Carolina
      • Asheville, North Carolina, United States, 28806
        • Messino Cancer Centers
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology- Nashville
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology-Sammons Cancer Center
      • Dallas, Texas, United States, 75201
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77002
        • The University of Texas MD Anderson Cancer Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53202
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. ≥ 18 years of age at the time of signing the informed consent form (ICF).
  2. Histologically or cytologically confirmed CCA/adenocarcinoma of biliary origin with radiological evidence of unresectable or metastatic disease.
  3. Documentation of FGFR2 fusion/rearrangement gene status
  4. Subjects must have received at least one line of prior chemotherapy and exactly one FDA approved FGFR inhibitor.

Exclusion Criteria:

  1. Prior receipt of two or more FGFR inhibitors, either approved or investigational drugs.
  2. Subjects with known brain or central nervous system (CNS) metastases that have radiologically or clinically progressed in the 28 days prior to initiation of therapy. Subjects with asymptomatic brain/CNS metastases or treated brain/CNS metastases that have been clinically stable for 14 days on steroids without escalation of steroids are eligible for enrollment.
  3. Subjects with a known concurrent malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, including those that have previously undergone potentially curative therapy.
  4. Subjects who have received prior systemic therapy or investigational study drug ≤ 5 half-lives or 14 days, whichever is shorter, prior to starting the study drug or who have not recovered (grade ≤ 1 or at pretreatment baseline except tolerable grade 2 alopecia, fatigue/asthenia, and neuropathy due to trauma) from adverse events (AEs) of prior therapy.
  5. Concurrent anticancer therapy including chemo-, immune-, or radiotherapy. Hormone therapy may be allowed with Sponsor approval.
  6. Subjects who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting the study drug or who have not recovered from AEs of prior therapy.
  7. Subjects with uncontrolled hypertension (defined as blood pressure of ≥ 150 mm Hg systolic and/or ≥ 90 mm Hg diastolic despite adequate treatment with antihypertensive medications at screening)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tinengotinib 8 mg QD
Tinengotinib will be administered in 28-day cycles.
Drug: Tinengotinib 8 mg
Subjects randomized to receive tinengotinib will receive a starting dose of either 8 mg QD., self-administered orally QD in 28-day cycles.
Experimental: Tinengotinib 10 mg QD
Tinengotinib will be administered in 28-day cycles.
Drug: Tinengotinib 10 mg
Subjects randomized to receive tinengotinib will receive a starting dose of either10 mg QD., self-administered orally QD in 28-day cycles.
Active Comparator: Physician's Choice
Physician's Choice treatments include FOLFOX or FOLFIRI
Drug: Physician's Choice
For subjects receiving FOLFOX or FOLFIRI, the subject will receive treatment every two weeks, with two administrations per each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Incidence, duration, and severity of adverse events (AEs)
Time Frame: Up to 30 days from study discontinuation
As assessed per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (or the most current version).
Up to 30 days from study discontinuation
Part B: PFS by BICR
Time Frame: From first study drug administration until the date of first documented progression assessed by BICR or date of death from any cause, whichever came first, assessed up to 24 months
Progression-free survival (PFS) by BICR: PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or date of death due to any cause, whichever is earlier.
From first study drug administration until the date of first documented progression assessed by BICR or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: ORR by Investigator
Time Frame: Through study completion, an average of 9 months.
ORR:objective response rate (ORR), the proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.
Through study completion, an average of 9 months.
Part A: DOR by Investigator
Time Frame: Through study completion, an average of 9 months.
Duration of response for CR or PR based on RECIST version 1.1.
Through study completion, an average of 9 months.
Part B:Overall Survival (OS)
Time Frame: From first study drug administration until the date of death from any cause, assessed up to 24 months.
OS is defined as the time from date of randomization to date of death of any cause.
From first study drug administration until the date of death from any cause, assessed up to 24 months.
Part B: Objective Response Rate (ORR) by BICR and by Investigator:
Time Frame: Through study completion, an average of 9 months.
The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.
Through study completion, an average of 9 months.
Part B: Duration of Response (DOR) by BICR and by Investigator
Time Frame: Through study completion, an average of 9 months.
Duration of response for CR or PR based on RECIST version 1.1.
Through study completion, an average of 9 months.
Part B: PFS by Investigators per RECIST v1.1.
Time Frame: From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

TransThera Sciences (Nanjing), Inc.

Investigators

  • Principal Investigator: Milind Javle, MD, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2023

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

June 29, 2023

First Submitted That Met QC Criteria

July 7, 2023

First Posted (Actual)

July 17, 2023

Study Record Updates

Last Update Posted (Actual)

July 6, 2026

Last Update Submitted That Met QC Criteria

July 1, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TT420C2308

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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