Tinengotinib for Bile Duct Cancer

(FIRST-308 Trial)

Recruiting at 92 trial locations

Overseen By Hui Wang

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing an oral medication called Tinengotinib for patients with a specific type of bile duct cancer that has not responded to other treatments. The medication works by blocking a protein that helps cancer cells grow. The goal is to see if Tinengotinib can slow down or stop the cancer in these patients.

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.

What data supports the effectiveness of the drug Tinengotinib for bile duct cancer?

The research highlights that targeted therapies have shown promise in treating biliary tract cancers, with several drugs approved for specific genetic mutations. While Tinengotinib is not directly mentioned, the success of other targeted therapies suggests potential for similar drugs in treating this cancer type. ^{1 2 3 4 5}

What makes Tinengotinib unique for treating bile duct cancer?

Tinengotinib is unique because it is a targeted therapy, which means it specifically aims at certain genetic changes in cancer cells, unlike traditional chemotherapy that affects all rapidly dividing cells. This approach is part of precision oncology, which uses drugs designed to target specific genetic alterations in cancers, potentially leading to better outcomes and fewer side effects. ^{1 2 6 7 8}

Research Team

Milind Javle

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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 am 18 years old or older.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Physician's Choice (Chemotherapy)
• Tinengotinib (FGFR Inhibitor)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

TransThera Sciences (Nanjing), Inc.

Lead Sponsor

Trials

15

Recruited

910+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2021]

2. England 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. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targetable Molecular Alterations in the Treatment of Biliary Tract Cancers: An Overview of the Available Treatments. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. Switzerland 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. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Immunotherapy in biliary tract cancers: Current evidence and future perspectives. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

Systemic treatment of advanced or recurrent biliary tract cancer. [2021]