Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations

NCT07328919 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: TT00420CN18
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 20

Brief Summary

This is an open-label, randomized, controlled, multicenter, phase III clinical study designed to evaluate the efficacy and safety of TT-00420 tablets as monotherapy versus chemotherapy in subjects with unresectable advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions/rearrangements or mutations, who have experienced recurrence or progression after prior first-line systemic chemotherapy.

Conditions

Intrahepatic Cholangiocarcinoma (Icc); Advanced Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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)

• Overall Survival (OS)

  From first study drug administration until the date of death from any cause, assessed up to 24 months.

• PFS by Investigators per 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.

• Objective Response Rate (ORR) by BICR and by Investigator

  Through study completion, an average of 9 months.

• Duration of Response (DOR) by BICR and by Investigator

  Through study completion, an average of 9 months.

• Disease Control Rate (DCR)

  Through study completion, an average of 9 months.

Study Arms (2)

Arm A (TT-00420 monotherapy)

EXPERIMENTAL

The starting dose of TT-00420 tablets is 10 mg QD (5 mg per tablet, 2 tablets), administered orally and taken continuously.

Drug: TT-00420 (tinengotinib)

Arm B (chemotherapy)

ACTIVE COMPARATOR

Chemotherapy includes mFOLFOX regimen, XELIRI regimen or irinotecan monotherapy.

Drug: Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine

Interventions

TT-00420 (tinengotinib) DRUG

Subject will receive TT-00420 (tinengotinib) once daily in 28-day cycles with initial dosage of 10 mg QD per protocol defined schedule.

Arm A (TT-00420 monotherapy)

Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine DRUG

Subjects will receive chemotherapy (mFOLFOX regimen, XELIRI regimen, or irinotecan monotherapy). The dosing schedule involves intravenous administration or oral intake every two weeks (except for capecitabine). Treatment continues until the occurrence of confirmed disease progression, intolerable toxicities, withdrawal of informed consent, death, or other reasons specified in the protocol (whichever occurs first). Among these, subjects receiving the mFOLFOX regimen are limited to a maximum of 6 treatment cycles (approximately 12 administrations).

Arm B (chemotherapy)

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 intrahepatic cholangiocarcinoma.
• Subjects diagnosed with stage III or IV intrahepatic cholangiocarcinoma according to the American Joint Committee on Cancer (AJCC) 8th Edition (2018) staging system, and assessed by the investigator as not eligible for curative surgical resection.
• Subjects who have experienced recurrence or progression after receiving only one prior line of systemic chemotherapy combined with immunotherapy (PD-1/PD-L1 inhibitor), with or without targeted therapy. Sequential immunotherapy following the completion of chemotherapy cycles is also considered part of the first-line combined regimen. First-line systemic chemotherapy is defined as gemcitabine/capecitabine with or without a platinum-based agent.
• Note: Recurrence within 6 months after completion of adjuvant or neoadjuvant therapy will be considered as a line of systemic therapy. Local treatments do not count as systemic therapy.
• The presence of FGFR2 gene fusion/rearrangement or mutation must be confirmed by detection using tumor tissue samples provided by the patient and analyzed by a central laboratory.
• At least one radiographically measurable lesion must be present according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• ECOG ≤ 1.
• Subjects must have adequate organ and bone marrow function.

You may not qualify if:

• Subjects with a history of prior treatment with TT-00420 tablets.
• Subjects with a known severe allergic reaction to any agent in the study and for whom no alternative study treatment is available.
• Subjects receiving corticosteroid therapy for CNS metastases are also ineligible.
• Concurrent active malignancy requiring active treatment. Malignancies diagnosed \>5 years ago without the need for treatment, as well as cured localized tumors such as basal cell carcinoma of the skin, carcinoma in situ of the cervix, or papillary thyroid carcinoma, are allowed.
• Administration of other anti-tumor drugs prior to randomization with an interval of ≤ 5 half-lives or 14 days (whichever is shorter), or failure to recover from adverse events of prior therapies (except for adverse events of ≤ Grade 1, or ≤ Grade 2 events judged by the investigator as not constituting a safety risk).
• Prior radiation therapy (large-field radiotherapy within 4 weeks, or local palliative radiotherapy within 2 weeks, before randomization), or failure to recover from related adverse events, is excluded. However, initiation of the investigational drug during the washout period is permitted with sponsor approval, if the investigator believes it is in the subject's best interest based on a favorable benefit-risk assessment.
• Subjects who have undergone major surgery within 4 weeks prior to randomization, or who have not recovered from related adverse events (with the exception of ≤ Grade 1 events or non-risk Grade 2 events per investigator's judgment), are excluded.
• 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 (20)

Anhui Provincial Hospital

Hefei, Anhui, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, China

Location

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Location

Zhongnan hospital of Wuhan University

Wuhan, Hubei, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Location

Jinan Central Hospital

Jinan, Shandong, China

Location

Shandong Cancer Hospital

Jinan, Shandong, China

Location

Sichuan Cancer Hospital

Chengdu, Sichuan, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

Beijing Cancer Hospital

Beijing, China

Location

Beijing Tsinghua Changgung Hospital

Beijing, China

Location

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, China

Location

Peking Union Medical College Hospital

Beijing, China

Location

Eastern Hepatobiliary Surgery Hospital

Shanghai, China

Location

Fudan University Shanghai Cancer Hospital

Shanghai, China

Location

Zhongshan Hospital, Fudan University

Shanghai, China

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension

Interventions

Oxaliplatin; Fluorouracil; Leucovorin; Irinotecan; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Caixia Sun

CONTACT

025-58216298; sun_caixia@transtherabio.com

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: December 26, 2025
• First Posted: January 9, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 9, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (20)