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

Cholangiocarcinoma Clinical Trial

— FIRST-308  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05948475
• Other study ID #: TT420C2308
• Status: Recruiting
• Phase: Phase 3
• Start date: December 20, 2023
• Est. completion date: August 2026

Study information

• Verified date: May 2024
• Source: TransThera Sciences (Nanjing), Inc.
• Contact: Jean Fan, MD
• Phone: 86-25-86901107
• Email: fan_jean[@]transtherabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: August 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cholangiocarcinoma

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Austria	Ordensklinikum Linz GmbH	Linz
Austria	Landesklinikum Wiener Neustadt	Wiener Neustadt
Belgium	Universitair Ziekenhuis Antwerpen	Antwerp
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitair Ziekenhuis Leuven	Leuven
France	Institut Sainte Catherine - Institut du Cancer Avignon Provence	Avignon
France	Centre Hospitalier Régional Universitaire de Besançon	Besancon
France	Hopital Beaujon	Clichy
France	Hopital Franco-Britannique - Fondation Cognacq-Jay	Levallois-Perret
France	Clinique de la Sauvegarde	Lyon
France	Centre Hospitalier Universitaire de Montpellier	Montpellier
France	Hopital Saint Antoine	Paris
France	Institut de Cancerologie Gustave Roussy	Villejuif
Germany	Krebszentrum Reutlingen	Baden
Germany	Krankenhaus Nordwest gGmbH	Frankfurt
Germany	Asklepios Klinik Altona	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaetsklinikum Heidelberg (UKHD) - Nationales Centrum fuer Tumorerkrankungen Heidelberg (NCT)	Heidelberg
Germany	Ludwig-Maximilians-Universität München Kum	München
Italy	Clinica Oncologica, Ospedali Riuniti Umberto 1	Ancona
Italy	Candiolo Cancer Institute - FPO IRCCS	Candiolo
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Istituto Europeo di Oncologia IRCCS	Milan
Italy	ASST Grande Ospedale Metropolitano Niguard	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Azienda Ospedaliera Universitaria Luigi Vanvitelli	Napoli
Italy	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale	Napoli
Italy	Azienda Ospedaliera Universitaria di Parma	Parma
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	Humanitas Research Hospital	Rozzano
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte	Siena
Italy	AOUI Verona - Ospedale Borgo Roma	Verona
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Gyeongsang National University Hospital	Jinju-si	Gyeongsangnam-do
Korea, Republic of	CHA Bundang Medical Center	Seongnam-si	Gyeonggi-do
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Health System - Severance Hospital	Seoul
Netherlands	Amsterdam UMC, location AMC	Amsterdam
Poland	Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie	Warszawa
Portugal	Fundação Champalimaud	Lisboa
Portugal	Centro Hospitalar Lisboa Norte CHLN EPE - Hospital de Santa Maria	Lisbon
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario Reina Sofa	Cordoba
Spain	Clinica Universidad de Navarra	Madrid
Spain	HM Hospital Universitario Madrid Sanchinarro - CIOCC	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Clinico Universitario de Santiago de Compostela	Santiago De Compostela
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	Chang Gung Memorial Hospital CGMH - Kaohsiung Branch	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Royal Marsden Hospital NHS	London
United Kingdom	UCG-1st floor central	London
United Kingdom	The Christie NHS Foundation Trust - Christie Hospital	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United States	University of Michigan	Ann Arbor	Michigan
United States	Messino Cancer Centers	Asheville	North Carolina
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	The University of Chicago Hospitals	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Texas Oncology-Sammons Cancer Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford	Detroit	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota- Masonic Cancer Center, M Health Fairview	Minneapolis	Minnesota
United States	Tennessee Oncology- Nashville	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	UCLA Medical Center	Santa Monica	California
United States	Stanford Cancer Center	Stanford	California
United States	The University of Kansas Cancer Center	Westwood	California
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
TransThera Sciences (Nanjing), Inc.

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Part A: ORR by Investigator	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.
Secondary	Part A: DOR by Investigator	Duration of response for CR or PR based on RECIST version 1.1.	Through study completion, an average of 9 months.
Secondary	Part B:Overall Survival (OS)	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.
Secondary	Part B: Objective Response Rate (ORR) by BICR and by Investigator:	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.
Secondary	Part B: Duration of Response (DOR) by BICR and by Investigator	Duration of response for CR or PR based on RECIST version 1.1.	Through study completion, an average of 9 months.
Secondary	Part B: PFS by Investigators per RECIST v1.1.	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.