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

NCT05948475 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: TT420C2308
• Study Type: interventional
• Target: 200
• Locations: 13 countries
• Sites: 87

Brief Summary

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

Conditions

Cholangiocarcinoma

Keywords

Refractory/Relapsed Cholangiocarcinoma

Outcome Measures

Primary Outcomes (2)

• Part A: Incidence, duration, and severity of adverse events (AEs)

  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

  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 Outcomes (6)

• Part A: ORR by Investigator

  Through study completion, an average of 9 months.

• Part A: DOR by Investigator

  Through study completion, an average of 9 months.

• Part B:Overall Survival (OS)

  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:

  Through study completion, an average of 9 months.

• Part B: Duration of Response (DOR) by BICR and by Investigator

  Through study completion, an average of 9 months.

Study Arms (3)

Tinengotinib 8 mg QD

EXPERIMENTAL

Tinengotinib will be administered in 28-day cycles.

Drug: Tinengotinib 8 mg

Tinengotinib 10 mg QD

EXPERIMENTAL

Tinengotinib will be administered in 28-day cycles.

Drug: Tinengotinib 10 mg

Physician's Choice

ACTIVE COMPARATOR

Physician's Choice treatments include FOLFOX or FOLFIRI

Drug: Physician's Choice

Interventions

Physician's Choice DRUG

For subjects receiving FOLFOX or FOLFIRI, the subject will receive treatment every two weeks, with two administrations per each 28-day cycle.

Physician's Choice

Tinengotinib 8 mg DRUG

Subjects randomized to receive tinengotinib will receive a starting dose of either 8 mg QD., self-administered orally QD in 28-day cycles.

Tinengotinib 8 mg QD

Tinengotinib 10 mg DRUG

Subjects randomized to receive tinengotinib will receive a starting dose of either10 mg QD., self-administered orally QD in 28-day cycles.

Tinengotinib 10 mg QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Prior receipt of two or more FGFR inhibitors, either approved or investigational drugs.
• 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.
• 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.
• 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.
• Concurrent anticancer therapy including chemo-, immune-, or radiotherapy. Hormone therapy may be allowed with Sponsor approval.
• 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.
• 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)

Sponsors & Collaborators

• TransThera Sciences (Nanjing), Inc.: lead

Study Sites (87)

UCLA Medical Center

Santa Monica, California, 90401, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

The University of Kansas Cancer Center

Westwood, Los Angeles, California, 90024, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

The University of Chicago Hospitals

Chicago, Illinois, 60601, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48103, United States

Location

Henry Ford

Detroit, Michigan, 48201, United States

Location

University of Minnesota- Masonic Cancer Center, M Health Fairview

Minneapolis, Minnesota, 55455, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Messino Cancer Centers

Asheville, North Carolina, 28806, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Tennessee Oncology- Nashville

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37203, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75201, United States

Location

Texas Oncology-Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77002, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53202, United States

Location

Ordensklinikum Linz GmbH

Linz, Austria

Location

Landesklinikum Wiener Neustadt

Wiener Neustadt, Austria

Location

Universitair Ziekenhuis Antwerpen

Antwerp, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, Belgium

Location

Institut Sainte Catherine - Institut du Cancer Avignon Provence

Avignon, France

Location

Centre Hospitalier Régional Universitaire de Besançon

Besançon, France

Location

Hopital Beaujon

Clichy, France

Location

Hopital Franco-Britannique - Fondation Cognacq-Jay

Levallois-Perret, France

Location

Clinique de la Sauvegarde

Lyon, France

Location

Centre Hospitalier Universitaire de Montpellier

Montpellier, France

Location

Hopital Saint Antoine

Paris, France

Location

Institut de Cancerologie Gustave Roussy

Villejuif, France

Location

Krebszentrum Reutlingen

Baden, Germany

Location

Krankenhaus Nordwest gGmbH

Frankfurt, Germany

Location

Asklepios Klinik Altona

Hamburg, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Universitaetsklinikum Heidelberg (UKHD) - Nationales Centrum fuer Tumorerkrankungen Heidelberg (NCT)

Heidelberg, Germany

Location

Ludwig-Maximilians-Universität München Kum

München, Germany

Location

Clinica Oncologica, Ospedali Riuniti Umberto 1

Ancona, Italy

Location

Candiolo Cancer Institute - FPO IRCCS

Candiolo, 10060, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

Location

Istituto Europeo di Oncologia IRCCS

Milan, Italy

Location

ASST Grande Ospedale Metropolitano Niguard

Milan, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Azienda Ospedaliera Universitaria Luigi Vanvitelli

Naples, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, Italy

Location

Azienda Ospedaliera Universitaria di Parma

Parma, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, Italy

Location

Humanitas Research Hospital

Rozzano, Italy

Location

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, Italy

Location

AOUI Verona - Ospedale Borgo Roma

Verona, Italy

Location

Amsterdam UMC, location AMC

Amsterdam, 1105 AZ, Netherlands

Location

Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie

Warsaw, Poland

Location

Centro Hospitalar Lisboa Norte CHLN EPE - Hospital de Santa Maria

Lisbon, Portugal

Location

Fundação Champalimaud

Lisbon, Portugal

Location

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Gyeongsang National University Hospital

Jinju, Gyeongsangnam-do, 52727, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Dong-A University Hospital

Busan, 49201, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Yonsei University Health System - Severance Hospital

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d´Hebron

Barcelona, Spain

Location

Hospital Universitario Reina Sofa

Córdoba, Spain

Location

Clinica Universidad de Navarra

Madrid, Spain

Location

HM Hospital Universitario Madrid Sanchinarro - CIOCC

Madrid, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Location

Hospital Universitario 12 de octubre

Madrid, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Clinica Universidad de Navarra

Pamplona, Spain

Location

Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

Chang Gung Memorial Hospital CGMH - Kaohsiung Branch

Kaohsiung City, 833401, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Royal Marsden Hospital NHS

London, United Kingdom

Location

UCG-1st floor central

London, United Kingdom

Location

The Christie NHS Foundation Trust - Christie Hospital

Manchester, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Milind Javle, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 17, 2023
• Study Start: December 20, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 6, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (11); BE (3); IT (13); NL (1); AU (2); PT (2); US (19); ES (12); DE (6); FR (8); GB (4); PL (1); TW (5)