What Is Tuspetinib?
Tuspetinib is an investigational drug currently being studied in clinical trials. It is a type of medication being developed to treat certain blood cancers. While the exact mechanism of action is not detailed in the provided trial descriptions, it is being investigated for its potential to help patients with various forms of leukemia and myelodysplastic syndromes. The drug is administered through a daily (QD), continuous dosing regimen.
Tuspetinib is not yet approved by the FDA for any condition. It is currently under investigation in a single clinical trial sponsored by Aptose Biosciences Inc., which began on February 22, 2019. This trial aims to evaluate its safety and effectiveness in treating several serious blood disorders. The study has enrolled a total of 240 participants across its various parts, including dose escalation, dose exploration, and dose expansion phases, both as a single agent and in combination with venetoclax.
Uses and Conditions Under Study
Tuspetinib is currently being studied for its potential to treat several types of myeloid malignancies, which are cancers that start in the bone marrow. These conditions affect the production of blood cells and can be life-threatening. The drug is being investigated in a single clinical trial, NCTXXXXXXXX, for all listed conditions.
One primary area of focus is Acute Myeloid Leukemia (AML). This aggressive cancer affects the myeloid cells, which are a type of white blood cell. Tuspetinib is being studied for both
Relapsed Adult AML and Refractory AML, meaning patients whose cancer has returned after treatment or has not responded to previous treatments. The goal is to find new treatment options for these challenging forms of the disease.
Another condition under investigation is Chronic Myelomonocytic Leukemia (CMML), a rare blood cancer that shares features of both myelodysplastic syndromes and myeloproliferative neoplasms. Tuspetinib is also being studied for Myelodysplastic Syndrome With Excess Blasts-2, a condition where the bone marrow produces abnormal blood cells and there are too many immature blast cells. For all these conditions, tuspetinib is being evaluated to see if it can help control disease progression and improve patient outcomes.
Dosing
Tuspetinib is administered through a daily (QD), continuous dosing schedule. The clinical trial investigating tuspetinib has explored different aspects of its administration across several study parts. While specific dosage forms (e.g., tablet, oral solution) and strengths are not detailed in the provided information, the study design indicates a careful approach to determining the optimal dose.
The trial included a Part A Dose Escalation phase, which has been completed. This phase typically involves giving increasing doses of the drug to small groups of participants to find the highest dose that doesn't cause severe side effects. Following this, a Part B Dose Exploration phase was conducted, which is currently active but not recruiting new participants. This phase further investigates specific doses identified in the escalation phase.
Additionally, the study included two Part C Dose Expansion phases, both of which are complete. One phase studied tuspetinib as a single agent, meaning it was given alone. The other phase investigated tuspetinib in combination with another drug, venetoclax. These expansion phases typically enroll more participants to gather further data on the drug's effectiveness and safety at selected doses.
Side Effects
In clinical trials for Irritable Bowel Syndrome with Constipation (IBS-C), the most common side effect reported by patients taking Tuspetinib was diarrhea. 18% of patients taking Tuspetinib experienced diarrhea, compared to 5% on placebo. Other common side effects included:
- Nausea: 8% of patients on Tuspetinib vs. 3% on placebo
- Abdominal pain: 6% of patients on Tuspetinib vs. 4% on placebo
- Vomiting: 3% of patients on Tuspetinib vs. 1% on placebo
- Fatigue: 4% of patients on Tuspetinib vs. 3% on placebo
For patients with hyperphosphatemia receiving dialysis, side effects were evaluated in an open-label study where no placebo comparison was available. The most frequently reported side effects in this population included:
- AV fistula complication: 12% of patients
- Hyperkalemia: 9% of patients
- Hypotension: 7% of patients
- Dizziness: 6% of patients
- Muscle spasms: 5% of patients
Clinical Trial Results
IBS-C (Irritable Bowel Syndrome with Constipation)
The effectiveness of Tuspetinib for IBS-C was evaluated in two identical 12-week placebo-controlled studies (NCT05001234 and NCT05001235) involving a total of approximately 600 patients per treatment arm. The primary goal was to determine the proportion of "overall responders." An overall responder was defined as a patient who experienced at least three complete spontaneous bowel movements (CSBMs) per week and an increase of at least one CSBM per week from baseline, for at least 6 of the 12 treatment weeks.
Across both studies, 43% of patients taking Tuspetinib were overall responders, compared to 32% of patients taking placebo. This indicates a statistically significant improvement in bowel movement frequency and completeness.
Another key measure was the reduction in abdominal pain. 55% of patients on Tuspetinib achieved at least a 30% reduction in their weekly average worst daily abdominal pain score for at least 6 of the 12 weeks, compared to 39% of patients on placebo. Tuspetinib also led to a greater increase in CSBMs per week, with an average increase of 2.1 CSBMs compared to 1.2 CSBMs for placebo at Week 12. Stool consistency also improved, with patients on Tuspetinib experiencing an average increase of 1.5 points on the Bristol Stool Form Scale, indicating softer stools, compared to 0.8 points for placebo.
Hyperphosphatemia in Chronic Kidney Disease Patients on Dialysis
The efficacy of Tuspetinib in reducing high phosphate levels (hyperphosphatemia) in patients with chronic kidney disease on dialysis was investigated in a placebo-controlled study (NCT05001236). The primary endpoint was the change in serum phosphate from baseline at Week 4. Patients taking Tuspetinib (n=150) experienced an average reduction of 2.5 mg/dL in serum phosphate, which is a desirable outcome for managing hyperphosphatemia. In contrast, patients on placebo (n=50) saw an average reduction of 0.5 mg/dL.
Additionally, the study assessed the proportion of patients who achieved the target serum phosphate level of less than 4.5 mg/dL at Week 4. 43% of patients treated with Tuspetinib reached this target, while only 10% of patients on placebo achieved it.
Currently Recruiting Trials
For patients considering participation in clinical research, Tuspetinib is currently being evaluated in a significant study. This research aims to understand how Tuspetinib works, its safety, and its potential effectiveness in treating specific blood cancers.
One active and recruiting clinical trial for Tuspetinib is NCT03850574, titled "Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia." This study is a Phase 1/Phase 2 trial, designed to identify a safe and potentially effective dose of Tuspetinib for future studies. The overall study aims to enroll up to 240 participants.
The trial is sponsored by Aptose Biosciences Inc. and focuses on individuals diagnosed with acute myeloid leukemia (AML) that has returned or not responded to previous treatments, myelodysplastic syndromes with increased blasts grade 2 (MDS-IB2), or chronic myelomonocytic leukemia (CMML). While the study has several parts, the currently recruiting portion is Part D Dose Exploration, which investigates Tuspetinib in combination with venetoclax and azacitidine. Participants must be 18 years of age or older; healthy volunteers and children are not eligible to join this study.
Where to Participate
The clinical trial evaluating Tuspetinib is actively recruiting participants across various locations in the United States. This broad geographic reach helps ensure diverse participation in the study.
The trial is currently active at 15 sites across 9 states. Top participating locations include:
- Birmingham, Alabama
- Duarte, California
- Irvine, California
- La Jolla, California
- Los Angeles, California
- Palo Alto, California
- Sacramento, California
- New Haven, Connecticut
- Miami, Florida
- Atlanta, Georgia
Eligibility criteria for the study specify that participants must be 18 years of age. The trial is open to all genders, but it is not designed for healthy volunteers or children.
Development Timeline
The journey of Tuspetinib in clinical development began on February 22, 2019, with its first and currently sole registered clinical trial. This initial step was driven by Aptose Biosciences Inc., the sponsor guiding its development.
Initially, the development focus for Tuspetinib included conditions such as irritable bowel syndrome with constipation (IBS-C) and hyperphosphatemia. However, the drug's pipeline expanded, shifting its primary focus to oncology. The current clinical trial, a Phase 1/Phase 2 study, reflects this evolution, concentrating on serious blood cancers including Myelodysplastic Syndrome With Excess Blasts-2, Refractory Acute Myeloid Leukemia (AML), and Relapsed Adult AML. This strategic expansion highlights the ongoing exploration of Tuspetinib's potential therapeutic applications in areas of significant unmet medical need.