Intrahepatic Cholangiocarcinoma (Icc)Phase 3NCT07328919
Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations
A Phase 3 study testing TT-00420 (tinengotinib) and Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine in people with Intrahepatic Cholangiocarcinoma (Icc) and Advanced Cholangiocarcinoma, run by TransThera Sciences (Nanjing), Inc. at 20 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intrahepatic Cholangiocarcinoma (Icc), Advanced Cholangiocarcinoma
- What is being tested?
- TT-00420 (tinengotinib) and Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 20 sitesChina
- Study dates
- Jan 2026to 31 Dec 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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.
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- 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.
Who cannot join
- 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).
Trial locations and contacts
20 sites in 1 country. Contact the study team or a site near you to ask about taking part.
20 sites in 1 country
China20 sites
Beijing Cancer Hospital
Beijing
Lin Shen, MD
Beijing Tsinghua Changgung Hospital
Beijing
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing
Peking Union Medical College Hospital
Beijing
Hunan Cancer Hospital
Changsha, Hunan
Sichuan Cancer Hospital
Chengdu, Sichuan
West China Hospital of Sichuan University
Chengdu, Sichuan
Fujian Cancer Hospital
Fuzhou, Fujian
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong
Zhejiang Cancer Hospital
Hangzhou, Zhejiang
Anhui Provincial Hospital
Hefei, Anhui
Jinan Central Hospital
Jinan, Shandong
Shandong Cancer Hospital
Jinan, Shandong
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi
Nanjing Drum Tower Hospital
Nanjing, Jiangsu
Eastern Hepatobiliary Surgery Hospital
Shanghai
Fudan University Shanghai Cancer Hospital
Shanghai
Zhongshan Hospital, Fudan University
Shanghai
Zhongnan hospital of Wuhan University
Wuhan, Hubei
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan
About this study
Official title: A Phase III, Randomized Controlled, Open-Label, Multicenter Clinical Study Evaluating the Efficacy and Safety of TT-00420 Tablets Versus Chemotherapy in Patients With Surgically Unresectable Advanced or Metastatic Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations, Who Have Progressed or Relapsed After Prior First-Line Systemic Therapy
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.
Read the 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).
- Being tested
- TT-00420 (tinengotinib), Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine
- Medical subject headings
- Cholangiocarcinoma, Cirrhosis, Familial, with Pulmonary Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabineDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: TT-00420 (tinengotinib) |
| Arm B (chemotherapy) | Active comparator | Chemotherapy includes mFOLFOX regimen, XELIRI regimen or irinotecan monotherapy. Receives: Drug: Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
OS is defined as the time from date of randomization to date of death of any cause.
Measured: 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.
PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measured: 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
The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.
Measured: Through study completion, an average of 9 months.
Duration of Response (DOR) by BICR and by Investigator
Duration of response for CR or PR based on RECIST version 1.1.
Measured: Through study completion, an average of 9 months.
Disease Control Rate (DCR)
The proportion of subjects who achieved a complete response (CR) or a partial response (PR) or a stable disease (SD) based on RECIST version 1.1.
Measured: Through study completion, an average of 9 months.
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).
Measured: Up to 30 days from study discontinuation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2026
- Study startJan 2026 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intrahepatic Cholangiocarcinoma (Icc)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TransThera Sciences (Nanjing), Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07328919
- Sponsor's protocol ID
- TT00420CN18
- Status last verified
- Dec 2025
- First submitted
- 26 Dec 2025
- Last updated
- 9 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized Controlled, Open-Label, Multicenter Clinical Study Evaluating the Efficacy and Safety of TT-00420 Tablets Versus Chemotherapy in Patients With Surgically Unresectable Advanced or Metastatic Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations, Who Have Progressed or Relapsed After Prior First-Line Systemic Therapy
- ClinicalTrials.gov ID
- NCT07328919
- Acronym / sponsor ID
- TT00420CN18
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- TransThera Sciences (Nanjing), Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2026 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 9 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (TT-00420 monotherapy) | Experimental | Drug: TT-00420 (tinengotinib)The starting dose of TT-00420 tablets is 10 mg QD (5 mg per tablet, 2 tablets), administered orally and taken continuously. |
| Arm B (chemotherapy) | Active comparator | Drug: Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabineChemotherapy includes mFOLFOX regimen, XELIRI regimen or irinotecan monotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ≥ 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.
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Arm A (TT-00420 monotherapy) |
| Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabineSubjects 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). | Drug | Arm B (chemotherapy) |
Primary outcome
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.
6 secondary outcomes
Overall Survival (OS)
Time frame: 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.
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.
Objective Response Rate (ORR) by BICR and by Investigator
Time frame: Through study completion, an average of 9 months.
Duration of Response (DOR) by BICR and by Investigator
Time frame: Through study completion, an average of 9 months.
Disease Control Rate (DCR)
Time frame: Through study completion, an average of 9 months.
Incidence, duration, and severity of adverse events (AEs)
Time frame: Up to 30 days from study discontinuation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TT-00420 (tinengotinib) and Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine in people with Intrahepatic Cholangiocarcinoma (Icc) and Advanced Cholangiocarcinoma, run by TransThera Sciences (Nanjing), Inc. at 20 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Caixia Sun (025-58216298, sun_caixia@transtherabio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.