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

NCT ID: NCT07328919

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2030-12-31

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.

Detailed Description

Approximately 138 subjects will be enrolled. Eligible subjects will be randomized in a 2:1 ratio to one of the two arms: Arm A (TT-00420 tablet monotherapy) or Arm B (chemotherapy).

Conditions

Intrahepatic Cholangiocarcinoma (Icc); Advanced Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (TT-00420 monotherapy)

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

Group Type: EXPERIMENTAL

TT-00420 (tinengotinib)

Intervention Type: 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 B (chemotherapy)

Chemotherapy includes mFOLFOX regimen, XELIRI regimen or irinotecan monotherapy.

Group Type: ACTIVE_COMPARATOR

Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine

Intervention Type: 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).

Interventions

TT-00420 (tinengotinib)

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

Intervention Type: DRUG

Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. ≥ 18 years of age at the time of signing the informed consent form (ICF).

2. Histologically or cytologically confirmed intrahepatic cholangiocarcinoma.

3. 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.

4. 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.

5. 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.

6. At least one radiographically measurable lesion must be present according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

7. ECOG ≤ 1.

8. Subjects must have adequate organ and bone marrow function.

Exclusion Criteria

1. Subjects with a history of prior treatment with TT-00420 tablets.

2. Subjects with a known severe allergic reaction to any agent in the study and for whom no alternative study treatment is available.

3. Subjects receiving corticosteroid therapy for CNS metastases are also ineligible.

4. 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.

5. 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).

6. 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.

7. 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.

8. 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TransThera Sciences (Nanjing), Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Anhui Provincial Hospital

Hefei, Anhui, China

Fujian Cancer Hospital

Fuzhou, Fujian, China

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Zhongnan hospital of Wuhan University

Wuhan, Hubei, China

Hunan Cancer Hospital

Changsha, Hunan, China

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Jinan Central Hospital

Jinan, Shandong, China

Shandong Cancer Hospital

Jinan, Shandong, China

Sichuan Cancer Hospital

Chengdu, Sichuan, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Beijing Cancer Hospital

Beijing, , China

Beijing Tsinghua Changgung Hospital

Beijing, , China

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Peking Union Medical College Hospital

Beijing, , China

Eastern Hepatobiliary Surgery Hospital

Shanghai, , China

Fudan University Shanghai Cancer Hospital

Shanghai, , China

Zhongshan Hospital, Fudan University

Shanghai, , China

Countries

China

Central Contacts

Caixia Sun

Role: CONTACT

sun_caixia@transtherabio.com

025-58216298

Facility Contacts

Lin Shen, MD

Role: primary

Other Identifiers

TT00420CN18

Identifier Type: -

Identifier Source: org_study_id