Tinengotinib for Bile Duct Cancer

(FIRST-308 Trial)

Recruiting at 115 trial locations

Overseen By Hui Wang

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: TransThera Sciences (Nanjing), Inc.

Must be taking: FGFR inhibitors

Must not be taking: Anticancer therapy

Disqualifiers: Brain metastases, Concurrent malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Tinengotinib for people with bile duct cancer. It compares Tinengotinib to standard treatments chosen by doctors to determine which is more effective for those with a specific gene change (FGFR2 fusion/rearrangement) who have already tried other chemotherapy and an FGFR inhibitor. Participants should have bile duct cancer that has spread or cannot be removed by surgery and must have previously received at least one type of chemotherapy and one FGFR inhibitor. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to access a potentially effective treatment before it becomes widely available.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you should not have received any systemic therapy or investigational drugs within 14 days before starting the study drug. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tinengotinib is generally safe for patients. In earlier studies, patients with advanced cancers, such as bile duct cancer, received tinengotinib. The treatment appeared safe, even for those who had tried many other treatments before. Another study found that tinengotinib was safe when combined with another medication. These findings suggest that tinengotinib is likely safe for most people. However, individual responses can vary, and side effects may differ. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bile duct cancer?

Most treatments for bile duct cancer, like FOLFOX or FOLFIRI, focus on using a combination of chemotherapy drugs to attack cancer cells. However, Tinengotinib stands out because it is a targeted therapy that aims to precisely inhibit specific proteins involved in cancer cell growth. This approach could potentially minimize side effects compared to traditional chemotherapy. Researchers are excited about Tinengotinib because it may offer a more effective and tailored treatment option for patients, with the possibility of improved outcomes and quality of life.

What evidence suggests that this trial's treatments could be effective for bile duct cancer?

Research has shown that tinengotinib, one of the treatments studied in this trial, has promising effects against tumors in patients with bile duct cancer, particularly those with specific changes in their FGFR (fibroblast growth factor receptor) genes. Previous studies found that tinengotinib controlled the disease in about 74% of patients, with some experiencing tumor shrinkage. This treatment has been tested in patients who previously tried other FGFR inhibitors, suggesting it might work even when other treatments fail. These findings indicate that tinengotinib could be a hopeful option for those with advanced bile duct cancer. Participants in this trial may receive tinengotinib or a treatment chosen by their physician, such as FOLFOX or FOLFIRI. ^{2 6 7 8 9}

Who Is on the Research Team?

Milind Javle

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with bile duct cancer that can't be surgically removed or has spread, and have specific FGFR2 gene changes. Participants must have tried one chemotherapy and one approved FGFR inhibitor but not more than that. They shouldn't have worsening brain metastases, be on other cancer treatments, or have another progressing cancer.

Inclusion Criteria

My cancer has been tested for FGFR2 gene changes.

I've had one chemotherapy and one FGFR inhibitor treatment.

My cancer originates from the bile ducts and cannot be surgically removed or has spread.

Exclusion Criteria

I have been treated with two or more FGFR inhibitors.

I have another cancer, but it's either not spreading or doesn't need treatment right now, except for skin or cervical cancers.

My brain or CNS cancer has been stable for 14 days, or I have no symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive tinengotinib 8 mg QD, tinengotinib 10 mg QD, or Physician's Choice in 28-day cycles

9 months

Treatment Part B

Participants receive the recommended Part B dose or selected dose or Physician's Choice

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Physician's Choice
• Tinengotinib

Trial Overview

The study compares the effectiveness of a new drug called Tinengotinib (at two different doses) against treatments chosen by physicians in patients with cholangiocarcinoma who haven’t responded to previous therapies. It's a randomized controlled trial meaning participants are randomly assigned to receive either the experimental drug or standard treatment.

How Is the Trial Designed?

Group I: Tinengotinib 8 mg QD Experimental Treatment 1 Intervention

Tinengotinib will be administered in 28-day cycles.

Group II: Tinengotinib 10 mg QD Experimental Treatment 1 Intervention

Tinengotinib will be administered in 28-day cycles.

Group III: Physician's Choice Active Control 1 Intervention

Physician's Choice treatments include FOLFOX or FOLFIRI

Physician's Choice is already approved in European Union, United States for the following indications:

Approved in European Union as Chemotherapy for:

• Cholangiocarcinoma

Approved in United States as Chemotherapy for:

• Cholangiocarcinoma

Approved in European Union as Targeted Therapy for:

• FGFR-altered Cholangiocarcinoma

Approved in United States as Targeted Therapy for:

• FGFR-altered Cholangiocarcinoma

Who Is Running the Clinical Trial?

TransThera Sciences (Nanjing), Inc.

Lead Sponsor

Trials

15

Recruited

910+

Published Research Related to This Trial

Cholangiocarcinoma (CCA) is a significant type of liver cancer with genetic alterations in key genes like FGFRs and IDH1/2, which can be targeted for treatment.

Emerging precision oncology approaches using targeted therapies such as pemigatinib and ivosidenib show promise in treating metastatic CCA by specifically inhibiting the altered functions of these genes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology. Capuozzo, M., Santorsola, M., Landi, L., et al.[2023]

Comprehensive genomic profiling (CGP) tests, including blood-based options, are now widely used in clinical practice in Japan, allowing for the analysis of hundreds of cancer-related genes to guide treatment decisions.

In biliary tract cancer, CGP tests can identify druggable variants more frequently than in other cancers, with specific markers linked to reimbursed therapies, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Clinical Practice of Precision Medicine Using Comprehensive Genomic Profiling Tests in Biliary Tract Cancer in Japan. Kanai, M.[2023]

The LV5FU2-P chemotherapy regimen demonstrated a 34% objective response rate in 29 patients with advanced or metastatic biliary tract carcinoma, indicating its potential effectiveness in treating this challenging cancer.

The treatment was well-tolerated, with no treatment-related deaths and significant improvements in patient performance status and weight, although some patients experienced grade 3 toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma. Taïeb, J., Mitry, E., Boige, V., et al.[2020]

In a study of 88 patients with nonresectable biliary tract cancers, adding panitumumab to chemotherapy resulted in a higher overall response rate (45%) compared to bevacizumab (20%), suggesting potential benefits of panitumumab in treatment.

Despite the higher response rate with panitumumab, neither treatment showed a significant improvement in progression-free survival or overall survival, indicating that neither combination qualifies for further Phase III testing at this time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II trial of combination chemotherapy with panitumumab or bevacizumab for patients with inoperable biliary tract cancer without KRAS exon 2 mutations. Amin, NEL., Hansen, TF., Fernebro, E., et al.[2021]

Bile duct tumors are aggressive and typically have poor survival rates, with chemotherapy being the main treatment for advanced stages; however, immunotherapy is emerging as a promising alternative due to its potential for better outcomes and reduced toxicity.

Recent FDA approvals of immune checkpoint inhibitors for tumors with specific biomarkers (like microsatellite instability-high) mark significant progress, and combination therapies are showing encouraging results in enhancing the effectiveness of these immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in biliary tract cancers: Current evidence and future perspectives. Uson Junior, PLS., Araujo, RL.[2022]

Biliary tract cancer (BTC) often presents at an advanced stage, with chemotherapy being the primary treatment option; a triplet regimen of gemcitabine, cisplatin, and nab-paclitaxel has shown significant effectiveness.

Next-generation sequencing (NGS) is crucial for guiding molecular targeted therapies, particularly for intrahepatic cholangiocarcinoma (iCCA), with FGFR and IDH inhibitors showing promise as emerging treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic treatment of advanced or recurrent biliary tract cancer. Zhang, W., Zhou, H., Wang, Y., et al.[2021]

In a study of 72 patients with advanced biliary tract cancer (BTC), comprehensive genomic profiling (CGP) identified actionable genomic alterations in 58.3% of cases, suggesting that CGP can help guide targeted therapies.

Loss of CDKN2A/B was associated with shorter overall survival in patients with intrahepatic cholangiocarcinoma (ICC), indicating it may serve as a poor prognostic factor and highlighting the importance of CGP in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study. Takada, K., Kubo, T., Kikuchi, J., et al.[2022]

Biliary tract cancers (BTCs) are often diagnosed at an advanced stage with a poor prognosis, but recent studies show a high rate of targetable genetic alterations, particularly in intrahepatic cholangiocarcinoma (iCCA).

Several targeted therapies have been approved for advanced BTC, including ivosidenib for IDH1 mutations and futibatinib for FGFR2 fusions, highlighting the potential for personalized treatment strategies based on genetic profiling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targetable Molecular Alterations in the Treatment of Biliary Tract Cancers: An Overview of the Available Treatments. Valery, M., Vasseur, D., Fachinetti, F., et al.[2023]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.608

Tinengotinib in patients with advanced, metastatic ...

Tinengotinib has shown promising anti-tumor efficacy in CCA pts with FGFR fusion after prior FGFRi and in those with primary FGFR mutations.

2.

ccanewsonline.com

ccanewsonline.com/issues/2025/march-2025-vol-6-no-1/tinengotinib-efficacy-in-patients-with-advanced-cholangiocarcinoma-a-phase-2-trial

Tinengotinib Efficacy in Patients With Advanced ...

A phase 2 clinical trial of tinengotinib in patients with advanced cholangiocarcinoma showed promising antitumor efficacy.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04742959

NCT04742959 | Study of TT-00420 (Tinengotinib) Tablet ...

Based on preliminary efficacy results, Phase II will enroll additional patients in select indications to evaluate the efficacy of TT-00420 monotherapy. Arm B: ...

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)04220-0/fulltext

140P Tinengotinib (TT-00420) in combination with ...

All 31 pts were efficacy evaluable. The objective response rate (ORR) and disease control rate (DCR) were 19.4% and 74.2%, the mPFS reached 4.21 (95% CI, ...

5.

firstwordpharma.com

firstwordpharma.com/story/5976899

TransThera Publishes Translational Studies of ...

Ongoing clinical trials in the US and China have revealed the potential of tinengotinib to be efficacious in various solid tumors.

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.473

Tinengotinib (TT-00420) in combination with atezolizumab ...

Tinengotinib combined with PD-L1 has demonstrated promising antineoplastic activity in preclinical study. Here we present the preliminary data ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.434

Efficacy and safety results of FGFR1-3 inhibitor ...

Tinengotinib has promising clinical benefit for FGFR2 fusion CCA after prior FGFRi and for non-fusion FGFR alterations. Tinengotinib-related toxicities were ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05253053

To Evaluate Efficacy and Safety of TT-00420 (Tinengotinib ...

Arm B: TT-00420 tablet in combination with atezolizumab (Tecentriq®) Arm B will enroll patients with advanced biliary tract cancer. Phase Ib will be a dose ...

9.

academic.oup.com

academic.oup.com/oncolo/article/29/4/e514/7595477

First-In-Human Phase I Study of Tinengotinib (TT-00420), a ...

Tinengotinib was given to 48 patients with advanced solid tumors and was well tolerated, with favorable pharmacokinetics. Forty-one patients ( ...