Tinengotinib for Bile Duct Cancer
(FIRST-308 Trial)
Recruiting in Palo Alto (17 mi)
+92 other locations
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.
12345What 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.
12678Eligibility 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.
+1 more
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.
+4 more
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Tinengotinib 8 mg QDExperimental Treatment1 Intervention
Tinengotinib will be administered in 28-day cycles.
Group II: Tinengotinib 10 mg QDExperimental Treatment1 Intervention
Tinengotinib will be administered in 28-day cycles.
Group III: Physician's ChoiceActive Control1 Intervention
Physician's Choice treatments include FOLFOX or FOLFIRI
Physician's Choice is already approved in European Union, United States, 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of MichiganAnn Arbor, MI
UMass Memorial Medical CenterWorcester, MA
University of Minnesota- Masonic Cancer Center, M Health FairviewMinneapolis, MN
Texas Oncology-Sammons Cancer CenterDallas, TX
More Trial Locations
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Who Is Running the Clinical Trial?
TransThera Sciences (Nanjing), Inc.Lead Sponsor
References
Randomized Phase II trial of combination chemotherapy with panitumumab or bevacizumab for patients with inoperable biliary tract cancer without KRAS exon 2 mutations. [2021]Biliary tract cancers (BTC) are rare and often diagnosed in late stages with advanced, nonresectable disease. The targeted agents panitumumab and bevacizumab have shown promising outcomes in combination with chemotherapy in other gastrointestinal (GI) cancers. We wanted to investigate if panitumumab or bevacizumab was the most promising drug to add to chemotherapy. Eighty-eight patients were randomized to combination chemotherapy supplemented by either panitumumab 6 mg/kg or bevacizumab 10 mg/kg on Day 1 in Arm A and Arm B, respectively. All patients received gemcitabine 1000 mg/m2 on Day 1, oxaliplatin 60 mg/m2 on Day 1 and capecitabine 1000 mg/m2 twice daily from Days 1 to 7. Treatment was repeated every 2 weeks until progression or for a maximum of 6 months. At progression, crossover was made to the other treatment arm. The primary endpoint was progression-free survival (PFS) at 6 months. With 19 of 45 in Arm A and 23 of 43 in Arm B PFS at 6 months, the primary endpoint was not met. The overall response rate (ORR) was 45% vs 20% (P = .03), median PFS was 6.1 months vs 8.2 months (P = .13) and median overall survival (OS) was 9.5 months vs 12.3 months (P = .47) in Arm A and Arm B, respectively. Our study showed no consistent differences between adding panitumumab or bevacizumab to chemotherapy in nonresectable BTC and none of the two regimens qualify for testing in Phase III. However, we found a higher response rate in the panitumumab arm with potential implication for future trials in the neoadjuvant setting.
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]Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen.
Targetable Molecular Alterations in the Treatment of Biliary Tract Cancers: An Overview of the Available Treatments. [2023]Biliary tract cancers (BTCs) are rare tumours, most often diagnosed at an unresectable stage, associated with poor prognosis, with a 5-year survival rate not exceeding 10%. Only first- and second-line treatments are well codified with the combination of cisplatin-gemcitabine chemotherapy and immunotherapy followed by 5-FU and oxaliplatin chemotherapy, respectively. Many studies have shown that BTC, and more particularly intrahepatic cholangiocarcinoma (iCCA), have a high rate of targetable somatic alteration. To date, the FDA has approved several drugs. Ivosidenib targeting IDH1 mutations, as well as futibatinib and pemigatinib targeting FGFR2 fusions, are approved for pre-treated advanced CCA. The combination of dabrafenib and trametinib are approved for BRAFV600E mutated advanced tumours, NTRK inhibitors entrectinib and larotrectinib for tumours bearing NTRK fusion and prembrolizumab for MSI-H advanced tumours, involving a small percentage of BTC in these three settings. Several other potentially targetable alterations are found in BTC, such as HER2 mutations or amplifications or KRASG12C mutations and mutations in genes involved in DNA repair mechanisms. This review aims to clarify the specific diagnostic modalities for gene alterations and to summarize the results of the main trials and developments underway for the management of advanced BTC with targetable alterations.
Current Clinical Practice of Precision Medicine Using Comprehensive Genomic Profiling Tests in Biliary Tract Cancer in Japan. [2023]With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests, which are designed to measure more than hundreds of cancer-related genes at a time, have now been widely introduced into daily clinical practice. For the patients whose tumor samples are not fit for tissue-based CGP tests, a blood-based CGP test (liquid biopsy) is available as an alternative option. Three CGP tests, "OncoGuide NCC™Oncopanel System (124 genes)", "FoundationOne®CDx (324 genes)", and "Founda-tionOne®CDx Liquid (324 genes)", are now reimbursed by public insurance in 233 hospitals designated for cancer genomic medicine in Japan. In biliary tract cancer, the prevalence of druggable variants is relatively higher compared to other cancer types and the European Society for Medical Oncology recommends routine use of CGP tests for advanced biliary tract cancer to guide treatment options. The latest National Cancer Center Network guideline lists eight druggable markers (NTRK fusion, MSI-H, TMB-H, BRAF V600E, FGFR2 fusions/rearrangement, IDH1 mutations, RET fusion, and HER2 overexpression) and matched therapies. In Japan, matched therapies for four markers (NTRK, MSI-H, TMB-H, and FGFR2) are reimbursed by public insurance (as of September 2022). The progress of genomic profiling technology will contribute to the improvement of the dismal clinical outcomes of this disease in the future.
Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study. [2022]Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.
Immunotherapy in biliary tract cancers: Current evidence and future perspectives. [2022]Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors. These are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall survival. Strategies are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of significant importance. Recent Food and Drug Administration approvals of immune checkpoint inhibitors (ICI) for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct tumors. Despite limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease, drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.
Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology. [2023]Cholangiocarcinoma (CCA) is a malignant neoplasm arising in the epithelium of the biliary tract. It represents the second most common primary liver cancer in the world, after hepatocellular carcinoma, and it constitutes 10-15% of hepatobiliary neoplasms and 3% of all gastrointestinal tumors. As in other types of cancers, recent studies have revealed genetic alterations underlying the establishment and progression of CCA. The most frequently involved genes are APC, ARID1A, AXIN1, BAP1, EGFR, FGFRs, IDH1/2, RAS, SMAD4, and TP53. Actionable targets include alterations of FGFRs, IDH1/2, BRAF, NTRK, and HER2. "Precision oncology" is emerging as a promising approach for CCA, and it is possible to inhibit the altered function of these genes with molecularly oriented drugs (pemigatinib, ivosidenib, vemurafenib, larotrectinib, and trastuzumab). In this review, we provide an overview of new biologic drugs (their structures, mechanisms of action, and toxicities) to treat metastatic CCA, providing readers with panoramic information on the trajectory from "old" chemotherapies to "new" target-oriented drugs.
Systemic treatment of advanced or recurrent biliary tract cancer. [2021]Biliary tract cancer (BTC) is a disease entity comprising diverse epithelial tumors with features of cholangiocyte differentiation, and it includes cholangiocarcinoma (CCA) and gallbladder cancer (GBC). Depending on its anatomical location, cholangiocarcinoma is categorized as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Nearly two-thirds of patients with biliary tract cancer present with advanced disease at diagnosis and in 68-86% of resections the cancer eventually recurs either locoregionally or at a distance. Chemotherapy is the first-line therapy for advanced or recurrent BTC. With the development of next-generation sequencing (NGS)-guided molecular targeted therapy, more options are available for treatment of advanced BTC. Chemotherapy, and especially a triplet regimen based on gemcitabine/cisplatin/nab-paclitaxel, has had the most significant effect, and fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) combined with bevacizumab is promising. Molecular targeted therapy should be based on genome sequencing and appears essential to precision medicine. Fibroblast growth factor receptor (FGFR) inhibitors and isocitrate dehydrogenase (IDH) inhibitors are promising emerging targeted therapies mainly for iCCA. Other targeted therapies such as anti-human epidermal growth factor receptor-2 (HER2) therapies, MEK inhibitors, BRAF inhibitors, and poly ADP ribose polymerase (PARP) inhibitors had tentatively displayed efficacy. Further evaluations of combination strategies in particular are needed. An immune checkpoint inhibitor (ICI) alone is less efficacious, but an ICI in addition to chemotherapy or radiotherapy has resulted in a response according to many case series. However, ICIs are still being evaluated in several ongoing studies. Combination therapies have garnered attention because of interactions between signaling pathways of carcinogenesis in BTC.