TYRA-200 for Bile Duct Cancer
(SURF201 Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Tyra Biosciences, Inc
Must be taking: Fgfr inhibitors
Disqualifiers: Cardiovascular disease, Brain metastases, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TYRA-200 in cancers with FGFR2 activating gene alterations, including unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants must have received a prior FGFR inhibitor, so you may need to continue with certain treatments.
What data supports the effectiveness of the drug TYRA-200 for bile duct cancer?
The research highlights the potential of targeting tyrosine kinase growth factor receptors, like ErbB-2 and EGFR, which are overexpressed in some biliary tract cancers. This suggests that treatments targeting these receptors could be effective, although specific data on TYRA-200 is not provided.
12345Eligibility Criteria
Adults with advanced solid tumors, including intrahepatic cholangiocarcinoma with FGFR2 gene alterations who have tried or declined standard treatments. For Part B, they must have had a prior FGFR inhibitor and specific resistance mutations. Exclusions include significant past anti-FGFR therapy toxicity, high serum phosphorus despite treatment, eye conditions increasing risk of toxicity, uncontrolled heart disease, active brain metastases, GI issues affecting drug absorption, and pregnant or breastfeeding women.Inclusion Criteria
My advanced cancer has FGFR/FGF alterations and I've tried or refused all standard treatments.
My cancer has a specific mutation resistant to FGFR inhibitors, confirmed by an approved test.
I am 18 years old or older.
+7 more
Exclusion Criteria
My blood phosphorus levels are high despite treatment.
I do not have stomach or intestine problems affecting medication absorption.
I stopped a previous FGFR-targeted therapy due to severe side effects.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Part A: Dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of TYRA-200 to determine the optimal and maximum tolerated dose
28-day cycles
Regular visits as per cycle
Antitumor Activity Evaluation
Part B: Evaluation of preliminary antitumor activity of TYRA-200 in participants with specific FGFR2 mutations
28-day cycles
Regular visits as per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing TYRA-200's safety and effectiveness against tumors with FGFR2 gene changes. Participants take the oral medication daily in 28-day cycles. The study has two parts: dose escalation (Part A) to find a safe dosage and dose expansion (Part B) to further assess its effects at that dosage.
1Treatment groups
Experimental Treatment
Group I: Phase 1 Part A and Part BExperimental Treatment2 Interventions
TYRA-200 taken once daily by mouth in 28-day cycles
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
The Ohio State UniversityColumbus, OH
The University of Texas MD Anderson Cancer CenterHouston, TX
University of California San Francisco (UCSF)San Francisco, CA
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Who Is Running the Clinical Trial?
Tyra Biosciences, IncLead Sponsor
References
Experience with distal bile duct cancers in U.S. Veterans Affairs hospitals: 1987-1991. [2019]Treatment selection and results were reviewed in a population with distal bile duct cancers.
Capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective single-center study. [2015]Palliative chemotherapy is currently the primary therapeutic approach in the treatment of advanced biliary tract cancer (BTC). Our aim was to assess the efficacy and safety of capecitabine plus cisplatin as first-line chemotherapy for patients with advanced BTC and to analyze the relationship between the level of CA19-9 and clinical outcome.
Targeted medical therapy of biliary tract cancer: recent advances and future perspectives. [2023]The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted.
[Palliative therapy in cholangio- and gallbladder carcinoma]. [2015]Non-resectable cholangiocarcinoma and gallbladder carcinoma have a poor prognosis. In addition to the general aspects of "best supportive care", biliary drainage is an important part of the palliative treatment of patients with malignant biliary stenosis. Photodynamic therapy has led to an improved median survival in hilar cholangiocarcinoma in two controlled studies. The survival benefit of external radiation or intraluminal brachytherapy has not yet been convincingly demonstrated. Whether or not systemic chemotherapy should be applied is still under debate. A single study including advanced biliary and pancreatic cancer patients has demonstrated a survival benefit for the combined group. In recent years, new chemotherapy protocols have been applied, some with promising results. Intra-arterial chemotherapy and chemotherapeutically coated stents have not been evaluated well enough to be recommended outside clinical studies. Ablative therapies have been used in a limited number of patients only. Further studies are necessary to clarify whether these treatment modalities are effective.
Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers. [2018]Carcinomas of the biliary tract have a poor prognosis. It is important to understand the molecular genetic characteristics of these tumours in order to employ newer effective treatments and to improve patient prognosis. There is increasing evidence that overexpression of tyrosine kinase growth factor receptors such as ErbB-2, epidermal growth factor receptor (EGFR), and Met may play important roles in the development of biliary tract carcinomas. The aim of this study was to assess the potential for novel chemotherapies targeting these receptors. Overexpression of the tyrosine kinase receptor proteins was examined by immunohistochemistry in 221 biliary tract carcinomas, of which 28 were from the intrahepatic bile duct, 78 from the extrahepatic bile duct, 89 from the gall bladder, and 26 from the ampulla of Vater. Positively stained tumours were further examined for gene amplification by fluorescence in situ hybridization. Overexpression of ErbB-2 was found in 15.7%, 11.5%, and 5.1% of carcinomas of the gall bladder, ampulla of Vater, and extrahepatic bile duct, respectively, and gene amplification was present in 79% of these. Overexpression of EGFR was found in 8.1% of tumours with no predominant location and was also associated with gene amplification with high frequency (77%). Met overexpression, most frequent in intrahepatic bile duct carcinomas (21.4%), was not associated with gene amplification. It is proposed that the new adjuvant chemotherapies could be directed to carcinomas of the biliary tract in which ErbB-2 and EGFR are overexpressed.
Identification of bile survivin and carbohydrate antigen 199 in distinguishing cholangiocarcinoma from benign obstructive jaundice. [2018]To investigate whether bile survivin and carbohydrate antigen 199 (CA199) can be helpful in distinguishing cholangiocarcinoma (malignant obstructive jaundice) from benign obstructive jaundice.
Therapeutic implication of HER2 in advanced biliary tract cancer. [2018]Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC.
Liquid biopsy and multi-analyte testing guided treatment of HER2 positive periampullary adenocarcinoma with durable complete response after trastuzumab based therapy. [2020]Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum. Surgical resection followed by adjuvant therapy is considered as the standard of care treatment for these carcinomas. Despite several advances in diagnostics and therapeutics, only 5% of these patients have an overall survival of five years or more. Currently, there is a dearth of viable therapeutic targets for this disease. The role of HER2 in cancer biology has been studied extensively in several tumour subtypes, and HER2 based targeted therapies have shown to have therapeutic benefits on different cancers. In this case report, we present a case of HER2 positive distal common bile duct carcinoma - a subtype of periampullary carcinoma with multiple relapses where multi-analyte testing with Encyclopedic Tumor Analysis (ETA) (Exacta®) identified amplification and over expression of HER2 gene which was used as a potential target to treat the patient with trastuzumab. Synchronous in vitro chemosensitivity profiling on Circulating Tumor Asscociated Cells (C-TACs) isolated from blood aided us to design the personalized chemotherapeutic regimen with cyclophosphamide and methotrexate. The combination of trastuzumab with cyclophosphamide and methotrexate yielded excellent treatment response with the patient remaining in complete response till the last follow-up. Our study suggests HER2 directed therapy as a potent pathway for treatment in the subset of HER-2 amplified distal common bile duct carcinomas.
Comparison of serum biomarkers cifra 21-1 and ca 19-9 in biliary tract cancers. [2022]Biliary malignancy is common in Asia and has high fatality. CA 19-9 has been used in diagnosis of biliary malignancy but can be raised in benign obstructive jaundice as well. CYFRA 21-1 can have an important role in patients with biliary tract cancer. The objective of this study is to compare accuracy of biomarkers CYFRA 21-1 with CA 19-9 for diagnosis of biliary tract cancers and to correlate level of biomarkers with the stage of disease.