What side effects are associated with this type of intervention?

Common treatments for Myelofibrosis, particularly those involving tyrosine kinase inhibitors like ruxolitinib and fedratinib, often result in side effects such as anemia, thrombocytopenia, and gastrointestinal symptoms (e.g., diarrhea, nausea). Additionally, patients may experience fatigue, infections, and elevated liver enzymes. In some cases, more severe adverse events like grade ≥3 anemia and thrombocytopenia have been reported.

What prior FDA approvals exist?

The FDA has approved several treatments for Myelofibrosis, including ruxolitinib and fedratinib, which are Janus kinase (JAK) inhibitors. These drugs target the JAK-STAT pathway, which is often dysregulated in Myelofibrosis. Ruxolitinib was the first JAK1/JAK2 inhibitor approved for this condition, providing significant relief from symptoms and reduction in spleen size. Fedratinib, another JAK2 inhibitor, offers an alternative for patients who are resistant or intolerant to ruxolitinib. These treatments share a similar mechanism of action with TL-895, as they all aim to inhibit tyrosine kinase activity, albeit through different specific targets within the pathway.

What other types of research exist?

Promising novel alternatives to TL-895 for Myelofibrosis patients include JAK2 inhibitors such as ruxolitinib and other emerging JAK2 inhibitors that are in clinical trials. Additionally, pegylated interferon alpha-2a has shown high molecular response rates in patients with related myeloproliferative disorders. These treatments are being actively studied and may offer effective options for Myelofibrosis management.

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Tyrosine Kinase Inhibitor

TL-895 for Myelofibrosis

Q: What is the mechanism of action of this treatment?

The most common treatments for Myelofibrosis include JAK inhibitors such as ruxolitinib and fedratinib, which work by inhibiting the Janus kinase (JAK) pathway that is often overactive in Myelofibrosis patients. This inhibition helps reduce symptoms like splenomegaly and improves overall quality of life. Irreversible tyrosine kinase inhibitors, such as TL-895, target specific tyrosine kinases involved in the disease's pathogenesis, potentially offering more durable responses by permanently disabling these enzymes. These treatments are crucial as they address the underlying molecular abnormalities driving the disease, thereby providing symptomatic relief and potentially modifying disease progression.

Phase 2

Recruiting

Research Sponsored by Telios Pharma, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Palpable spleen measuring ≥5 cm below the LLCM or spleen volume of ≥450 cm³ by MRI or CT scan assessment

Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

Must not have

Prior treatment with any BTK or BMX inhibitors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 9 months

Summary

This trial tests TL-895, a strong oral medication that targets specific proteins to treat Myelofibrosis and Indolent Systemic Mastocytosis. It is for patients who haven't responded to other treatments or can't take certain therapies.

Who is the study for?

This trial is for adults over 18 with Myelofibrosis who have a large spleen, are in fairly good health otherwise, and haven't responded well to or can't take JAK inhibitor treatments. They shouldn't have had certain other cancer treatments recently or any past spleen surgery.

What is being tested?

The study tests TL-895, an oral drug designed to inhibit specific enzymes that may be involved in Myelofibrosis. It's aimed at patients whose disease has come back after treatment or who cannot tolerate current therapies.

What are the potential side effects?

Potential side effects of TL-895 could include issues related to liver and kidney function, blood disorders due to bone marrow suppression, gastrointestinal symptoms, fatigue, and possibly allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My spleen is enlarged, extending 5 cm below my ribcage or is larger than 450 cm³ on scans.

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I can take care of myself but might not be able to do heavy physical work.

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I have been diagnosed with a type of myelofibrosis according to WHO criteria.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not taken BTK or BMX inhibitors before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 9 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~9 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 9 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cohort 5: Determine the RP2D of TL-895

Cohorts 1-3: Determine the RP2D of TL-895

Secondary study objectives

Cohort 5: Changes in patient reported symptoms

Cohorts 1-3: Spleen volume reduction (SVR) rate

Trial Design

13Treatment groups

Experimental Treatment

Placebo Group

Group I: Cohort 5d, Indolent Systemic MastocytosisExperimental Treatment1 Intervention

TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Group II: Cohort 5c, Indolent Systemic MastocytosisExperimental Treatment1 Intervention

TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Group III: Cohort 5b, Indolent Systemic MastocytosisExperimental Treatment1 Intervention

TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Group IV: Cohort 5a, Indolent Systemic MastocytosisExperimental Treatment1 Intervention

TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with best supportive care (BSC).

Group V: Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/LExperimental Treatment1 Intervention

300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Group VI: Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/LExperimental Treatment1 Intervention

150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Group VII: Cohort 2b, JAKi Intolerant MyelofibrosisExperimental Treatment1 Intervention

300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Group VIII: Cohort 2a, JAKi Intolerant MyelofibrosisExperimental Treatment1 Intervention

150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Group IX: Cohort 1d, Relapsed/Refractory MyelofibrosisExperimental Treatment1 Intervention

450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Group X: Cohort 1c, Relapsed/Refractory MyelofibrosisExperimental Treatment1 Intervention

300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Group XI: Cohort 1b, Relapsed/Refractory MyelofibrosisExperimental Treatment1 Intervention

300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Group XII: Cohort 1a, Relapsed/Refractory MyelofibrosisExperimental Treatment1 Intervention

150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Group XIII: Cohort 5e, Indolent Systemic MastocytosisPlacebo Group1 Intervention

Placebo to match TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

TL-895

2020

Completed Phase 1

~10

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Myelofibrosis include JAK inhibitors such as ruxolitinib and fedratinib, which work by inhibiting the Janus kinase (JAK) pathway that is often overactive in Myelofibrosis patients. This inhibition helps reduce symptoms like splenomegaly and improves overall quality of life. Irreversible tyrosine kinase inhibitors, such as TL-895, target specific tyrosine kinases involved in the disease's pathogenesis, potentially offering more durable responses by permanently disabling these enzymes. These treatments are crucial as they address the underlying molecular abnormalities driving the disease, thereby providing symptomatic relief and potentially modifying disease progression.

Find a Location

Who is running the clinical trial?

Telios Pharma, Inc.Lead Sponsor

9 Previous Clinical Trials

1,478 Total Patients Enrolled

Media Library

TL-895 (Tyrosine Kinase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04655118 — Phase 2

$Myelofibrosis Research Study Groups: Cohort 5d, Indolent Systemic Mastocytosis, Cohort 5e, Indolent Systemic Mastocytosis, Cohort 5a, Indolent Systemic Mastocytosis, Cohort 5c, Indolent Systemic Mastocytosis, Cohort 5b, Indolent Systemic Mastocytosis, Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L, Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of ≥ 25 and < 50 × 109/L, Cohort 1d, Relapsed/Refractory Myelofibrosis, Cohort 1a, Relapsed/Refractory Myelofibrosis, Cohort 1b, Relapsed/Refractory Myelofibrosis, Cohort 1c, Relapsed/Refractory Myelofibrosis, Cohort 2a, JAKi Intolerant Myelofibrosis, Cohort 2b, JAKi Intolerant Myelofibrosis$