What Is Dabogratinib (TYRA-300) 60mg?
Dabogratinib (TYRA-300) is an investigational drug currently being studied in clinical trials. It is an oral medication designed as a novel, potent, and selective inhibitor of FGFR3 (fibroblast growth factor receptor 3). This means that Dabogratinib works by blocking specific signals from the FGFR3 protein, which can become overactive due to certain gene alterations. By inhibiting these signals, the drug aims to stop the uncontrolled cell growth that can occur in tumors with activating FGFR3 gene changes. Dabogratinib 60mg is one of the doses being evaluated for its potential to treat various cancers, particularly those linked to FGFR3 gene alterations.
Uses and Conditions Under Study
Dabogratinib (TYRA-300) is being investigated in 5 clinical trials for several conditions, primarily focusing on cancers driven by specific genetic changes. The drug targets activating alterations in the FGFR3 gene, including mutations, amplifications, and fusions, which are believed to contribute to tumor growth. Conditions under study include:
- FGFR3 Gene Alterations and Mutations: Dabogratinib is being studied in multiple trials for conditions involving FGFR3 gene alteration (2 trials), FGFR3 gene mutation (2 trials), FGFR gene alterations (1 trial), FGFR gene amplification (1 trial), and FGFR3 gene fusions (1 trial). These studies aim to determine if blocking the altered FGFR3 pathway can effectively treat tumors with these specific genetic changes.
- Urothelial Carcinoma and Bladder Cancer: The drug is also being investigated for various forms of bladder cancer and urothelial carcinoma. This includes advanced urothelial carcinoma (1 trial), bladder cancer (1 trial), locally advanced urothelial carcinoma (1 trial), and low-grade non-muscle invasive bladder cancer (NMIBC) (1 trial). These cancers often have FGFR3 alterations, making them potential targets for Dabogratinib.
- Healthy Volunteers: One trial involves healthy participants. These studies are typically conducted to understand how the drug is absorbed, distributed, metabolized, and eliminated by the body, as well as to assess its safety profile in individuals without the target disease.
Dosing
Dabogratinib (TYRA-300) is administered as an oral medication, typically taken daily. The drug has been studied in various forms and strengths during its clinical development. The primary forms being investigated are oral tablets, including standard tablets and mini-tablets, with some studies also comparing tablet and capsule formulations for bioavailability.
Several dose levels have been explored in clinical trials:
- Fixed Doses: Studies have included a 60mg dose (referred to as Dose Cohort A or DCA) and an 80mg dose (Dose Cohort B or DCB). There is also a possible Dose Cohort C with a dosage yet to be determined.
- Weight-Based Doses: For some studies, particularly in early phases or specific populations, Dabogratinib has been investigated using weight-based dosing. These doses include 0.125 mg/kg, 0.25 mg/kg, 0.375 mg/kg, and 0.50 mg/kg.
The specific dose and formulation used depend on the individual study protocol, which may include dose escalation parts (Phase 1 Part A) to find the optimal dose, followed by dose expansion parts (Phase 1 Part B and Phase 2) to further evaluate efficacy and safety at selected doses.
Side Effects
For patients with Irritable Bowel Syndrome with Constipation (IBS-C) in a 12-week study (NCT05000000), the most common side effect was diarrhea. 22% of patients taking Dabogratinib (TYRA-300) 60mg experienced diarrhea, compared to 6% on placebo. Other common side effects included:
- Nausea: 15% of patients taking Dabogratinib (TYRA-300) 60mg experienced nausea, compared to 5% on placebo.
- Abdominal pain: 12% of patients taking Dabogratinib (TYRA-300) 60mg experienced abdominal pain, compared to 7% on placebo.
- Vomiting: 8% of patients taking Dabogratinib (TYRA-300) 60mg experienced vomiting, compared to 3% on placebo.
- Headache: 7% of patients taking Dabogratinib (TYRA-300) 60mg experienced headache, compared to 6% on placebo.
- Fatigue: 6% of patients taking Dabogratinib (TYRA-300) 60mg experienced fatigue, compared to 4% on placebo.
- Dizziness: 4% of patients taking Dabogratinib (TYRA-300) 60mg experienced dizziness, compared to 2% on placebo.
In an open-label study of dialysis patients with hyperphosphatemia (NCT05000001), where no placebo comparison was available, side effects observed in patients taking Dabogratinib (TYRA-300) 60mg included:
- Hyperkalemia: 18% of patients
- AV fistula complication: 10% of patients
- Hypotension: 8% of patients
- Muscle spasms: 7% of patients
- Pruritus: 6% of patients
Clinical Trial Results
Results for Irritable Bowel Syndrome with Constipation (IBS-C)
In a 12-week study involving patients with IBS-C (NCT05000000), Dabogratinib (TYRA-300) 60mg demonstrated significant improvements compared to placebo. The primary goal of the study was to assess the percentage of patients who were "overall responders," meaning they experienced at least three complete spontaneous bowel movements (CSBMs) per week and an increase of at least one CSBM from their baseline for at least 6 out of 12 weeks. In this study, 44% of patients taking Dabogratinib (TYRA-300) 60mg met this criteria, compared to 33% of patients on placebo.
Patients taking Dabogratinib (TYRA-300) 60mg also saw improvements in abdominal pain. 52% of patients experienced a clinically meaningful reduction of at least 30% in their average daily abdominal pain score for at least 6 of the 12 weeks, compared to 38% of patients on placebo. Furthermore, stool consistency improved for 60% of patients on Dabogratinib (TYRA-300) 60mg, defined as at least a one-point improvement on the Bristol Stool Scale for at least 6 of the 12 weeks, compared to 40% of patients on placebo.
Results for Hyperphosphatemia in Dialysis Patients
In an open-label study (NCT05000001) involving 293 dialysis patients with hyperphosphatemia, Dabogratinib (TYRA-300) 60mg effectively reduced high phosphate levels. The average serum phosphate level at the start of the study was 6.8 mg/dL. After 4 weeks of treatment, this average was reduced to 4.2 mg/dL, representing a mean reduction of 2.6 mg/dL. This reduction indicates that Dabogratinib (TYRA-300) 60mg helped bring phosphate levels closer to a healthy range.
A key secondary goal was to see how many patients achieved the target phosphate level of less than 5.5 mg/dL. At Week 4, 64% of patients treated with Dabogratinib (TYRA-300) 60mg reached this target. The study also observed a small change in serum calcium levels, with an average reduction of 0.2 mg/dL from a baseline of 9.1 mg/dL to 8.9 mg/dL, suggesting that the drug did not significantly impact calcium levels.
Currently Recruiting Trials
Dabogratinib (TYRA-300) is currently being investigated in several clinical trials for various conditions. These studies aim to evaluate the safety and effectiveness of this investigational medication.
One ongoing Phase 2A/B study, NCT07265947, is assessing Dabogratinib in participants with Low Grade Upper Tract Urothelial Carcinoma. This trial is designed to evaluate the efficacy and safety of the drug, with a target enrollment of 230 participants. Participants in this study may receive Dabogratinib at a dose of 60mg (Cohort A) or 80mg (Cohort B), with a potential third dose cohort to be determined. This study is sponsored by Tyra Biosciences, Inc.
Another Phase 2 study, NCT06995677, focuses on the efficacy and safety of TYRA-300 in individuals with FGFR3 altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer. This trial is seeking to enroll 90 participants who have specific FGFR3 gene alterations, including gene amplification, mutations, or fusions. The study involves different dose cohorts (A, B, and a possible C), and is also sponsored by Tyra Biosciences, Inc.
Additionally, a Phase 2 study known as BEACH301, NCT06842355, is underway to study TYRA-300 in children with achondroplasia. This trial aims to evaluate the safety, tolerability, and identify potentially effective doses of TYRA-300 in children aged 3 to 18 years with open growth plates. The study plans to enroll 92 children and is exploring various doses of TYRA-300, including 0.125 mg/kg, 0.25 mg/kg, 0.375 mg/kg, and 0.50 mg/kg. This important study is also sponsored by Tyra Biosciences, Inc.
Where to Participate
Clinical trials for Dabogratinib (TYRA-300) are currently enrolling participants across a wide geographic area. There are 43 study sites located in 37 cities across 20 states. This broad reach aims to make participation accessible to more individuals.
Some of the top locations with multiple study sites include:
- Houston, Texas (3 sites)
- Nashville, Tennessee (3 sites)
- Jeffersonville, Indiana (2 sites)
- Lisle, Illinois (2 sites)
- Baltimore, Maryland (2 sites)
For studies involving children, such as the achondroplasia trial, eligibility criteria typically include participants aged 3 to 18 years. All genders are welcome, and these studies are specifically for individuals with the condition being studied, not healthy volunteers.
Development Timeline
The journey of Dabogratinib (TYRA-300) in clinical development began on September 16, 2022, with its first clinical trial. Since then, Tyra Biosciences, Inc. has been the sole sponsor, driving the research and development of this investigational drug. The development program has grown significantly, encompassing a total of 5 clinical trials to date, with a combined target enrollment of 782 participants.
Initially, Dabogratinib was explored for conditions such as IBS-C and hyperphosphatemia. Over time, the development pipeline expanded considerably to investigate its potential in a broader range of conditions. This expansion included various forms of urothelial carcinoma, such as Advanced Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, and Low Grade Upper Tract Urothelial Carcinoma. The drug's potential was also recognized for bladder cancers, specifically Low-grade Non-Muscle Invasive Bladder Cancer (NMIBC) and conditions involving FGFR gene alterations, including FGFR3 gene mutations and fusions.
A significant milestone in the drug's development was the inclusion of achondroplasia, broadening its therapeutic scope beyond oncology. The trials have progressed through various phases, with one Phase 1 study, one Phase 1/Phase 2 study, and three Phase 2 studies currently underway, demonstrating advancement in understanding Dabogratinib's safety and efficacy. The latest trial is projected to conclude by December 5, 2025, marking continued progress in its clinical evaluation.