TL-895 for Myelofibrosis

Recruiting at 59 trial locations

Overseen By Emily Houlihan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Telios Pharma, Inc.

Must not be taking: BTK inhibitors, JAKi, others

Disqualifiers: Splenectomy, Myeloproliferative disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

121 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TL-895, a potential drug for Myelofibrosis and Indolent Systemic Mastocytosis. Myelofibrosis is a rare blood disorder affecting blood cell production, while Indolent Systemic Mastocytosis involves an excess of mast cells, a type of white blood cell. The trial aims to determine if TL-895 can benefit those who haven't responded to other treatments. Participants should have Myelofibrosis or Indolent Systemic Mastocytosis and experience issues with current standard treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you have not taken JAKi treatment within 28 days before starting the study. If you are currently on JAKi, you will need to stop it at least 28 days before joining the trial.

Is there any evidence suggesting that TL-895 is likely to be safe for humans?

Research has shown that TL-895, a pill, may help treat Myelofibrosis and Indolent Systemic Mastocytosis. Although earlier studies have not fully detailed its safety, TL-895's advancement to this stage suggests it has been generally safe so far. In early trials, drugs must demonstrate basic safety to proceed. TL-895 targets specific areas, potentially reducing side effects. However, as with any new treatment, possible side effects remain under study, and participants are closely monitored for any negative reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Myelofibrosis?

Researchers are excited about TL-895 because it offers a fresh approach to treating myelofibrosis. Unlike current treatments, which often involve JAK inhibitors, TL-895 is a potent BTK (Bruton's tyrosine kinase) inhibitor. This mechanism targets specific molecular pathways involved in the disease's progression, potentially offering a new therapeutic angle. Furthermore, TL-895 is administered orally, making it a convenient option compared to some treatments that require hospital visits for infusions. This innovative approach could lead to more effective management of myelofibrosis with fewer side effects.

What evidence suggests that this trial's treatments could be effective for Myelofibrosis and Indolent Systemic Mastocytosis?

Research has shown that TL-895, a new medication, may help treat Myelofibrosis. In this trial, participants will receive TL-895 in various dosages across different cohorts. One study found that 36% of patients experienced a noticeable improvement in their symptoms after 24 weeks. Although no patients showed a major decrease in spleen size, an important sign of progress, most remained alive after an average of 12.4 months. TL-895 works by blocking certain enzymes that aid cancer cell growth, which may contribute to its effectiveness. Early results suggest it could be a promising treatment option, especially for those unable to use current JAK inhibitor medications. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

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

Exclusion Criteria

I have had my spleen removed or treated with radiation within the last 24 weeks.

I have not taken BTK or BMX inhibitors before.

I have (not) taken JAK inhibitors within the last 21 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TL-895 or placebo orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle

24 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TL-895

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort 5d, Indolent Systemic Mastocytosis Experimental Treatment 1 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 Mastocytosis Experimental Treatment 1 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 Mastocytosis Experimental Treatment 1 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 Mastocytosis Experimental Treatment 1 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/L Experimental Treatment 1 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/L Experimental Treatment 1 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 Myelofibrosis Experimental Treatment 1 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 Myelofibrosis Experimental Treatment 1 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 Myelofibrosis Experimental Treatment 1 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 Myelofibrosis Experimental Treatment 1 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 Myelofibrosis Experimental Treatment 1 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 Myelofibrosis Experimental Treatment 1 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 Mastocytosis Placebo Group 1 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.

Who Is Running the Clinical Trial?

Telios Pharma, Inc.

Lead Sponsor

Trials

11

Recruited

1,700+

Published Research Related to This Trial

TGF-β1 is significantly overexpressed in myelofibrosis (MF) patients and contributes to excessive collagen production, which worsens the disease, indicating its role in MF pathogenesis.

The ALK5 inhibitor galunisertib showed promising results in improving MF symptoms in mouse models, suggesting that targeting the TGF-β pathway could be an effective therapeutic strategy for treating MF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ALK5 inhibition in myelofibrosis. Yue, L., Bartenstein, M., Zhao, W., et al.[2020]

Ruxolitinib, a JAK2 inhibitor, has been shown to improve survival and reduce symptoms like splenomegaly in patients with intermediate-2 or high-risk myelofibrosis, indicating its efficacy in treating this condition.

The drug also decreases the JAK2 V617F allele burden in some patients, suggesting it has a beneficial molecular effect, and it has been approved for use in the United States and Europe based on clinical study results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Small molecular compounds for BCR/ABL-negative myeloproliferative neoplasms]. Nagai, T.[2021]

In a study of 1607 patients with essential thrombocythemia (ET), several clinical and molecular factors were identified as predictors of inferior myelofibrosis-free survival, including age over 60, male sex, palpable splenomegaly, and specific genetic mutations.

A new 'high molecular risk' category was established for patients with certain genetic profiles, showing significantly higher rates of fibrotic transformation over 10 and 20 years, indicating the need for closer monitoring and counseling for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients. Loscocco, GG., Guglielmelli, P., Gangat, N., et al.[2022]

In a study of 90 myelofibrosis patients who underwent allogeneic stem cell transplantation, MPL W515L mutations were identified in 2 patients, indicating its potential as a minimal residual disease (MRD) marker for monitoring remission.

Both patients with the MPL W515L mutation cleared it rapidly after transplantation and remained negative for a median follow-up of 19 months, suggesting that monitoring this mutation can effectively guide treatment decisions in JAK2V617F-negative myelofibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening and monitoring of MPL W515L mutation with real-time PCR in patients with myelofibrosis undergoing allogeneic-SCT. Alchalby, H., Badbaran, A., Bock, O., et al.[2012]

In a phase 1/2 trial involving 100 patients with high/intermediate-risk myelofibrosis, treatment with the JAK1/2 inhibitor momelotinib led to clinical improvement in 57% of patients, particularly in those without ASXL1 mutations and with low circulating blasts.

Despite some patients experiencing significant side effects, such as thrombocytopenia and peripheral neuropathy, the overall survival after discontinuation of momelotinib was similar to that of a comparable group of patients not receiving the treatment, suggesting that while momelotinib may provide some benefits, it does not significantly alter long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Momelotinib therapy for myelofibrosis: a 7-year follow-up. Tefferi, A., Barraco, D., Lasho, TL., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04655118

Study of TL-895 in Subjects With Myelofibrosis or Indolent ... This study evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20562147

Study of TL-895 in Subjects With Myelofibrosis This purpose of this study is to evaluate TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of ...

3. vjhemonc.com vjhemonc.com/video/ydupob6klze-phase-ii-study-update-of-tl-895-in-patients-with-myelofibrosis-with-severe-thrombocytopenia/

EHA 2023 | Phase II study update of TL-895 in patients with ... Dr Loschi shares some data from the first 11 patients including survival, spleen volume reduction and improvement in patient platelet counts. Dr ...

4. clinicaltrials.eu clinicaltrials.eu/inn/tl-895/

Tl-895 – Application in Therapy and Current Clinical ... Trials are measuring outcomes like tumor response, reduction in spleen volume, improvement in symptoms, and overall survival in patients with various cancers ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10431408/

P1038: TL-895, A FIRST-IN-CLASS, COVALENT BRUTON ... Ten (91%) pts were alive at data cut (median 12.4 mos). At Wk 24, four pts (36%) achieved TSS-50 (Fig. 1), despite no pts achieving SVR-35 (median SVR - ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04655118

Study of TL-895 in Subjects With Myelofibrosis or Indolent ... This study evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis.

7. orpha.net orpha.net/en/research-trials/clinical-trial/696480

Search for a clinical trial A Phase 2 Multicenter Study of TL-895 in Subjects with Myelofibrosis, Indolent Systemic Mastocytosis, Monoclonal Mast Cell Activation Syndrome, or Non ...

8. rarediseaseadvisor.com rarediseaseadvisor.com/hcp-resource/systemic-mastocytosis-clinical-trials/

Systemic Mastocytosis Clinical Trials TL-895 is an orally administered tyrosine kinase inhibitor with anti-inflammatory and anticancer properties. It targets, binds to, and inhibits tyrosine kinase, ...

9. clinicaltrials.eu clinicaltrials.eu/trial/study-of-tl-895-for-patients-with-relapsed-or-refractory-myelofibrosis-or-indolent-systemic-mastocytosis/

Study of TL-895 for Patients with Relapsed or Refractory ... This clinical trial is focused on studying the effects of a medication called TL-895 in individuals with certain blood-related conditions.

10. sciencedirect.com sciencedirect.com/science/article/pii/S2473952925000527

Systemic mastocytosis: current status and challenges in 2024 Study of TL-895 in subjects with myelofibrosis or indolent systemic mastocytosis. Clinical Trials gov identifier: NCT04655118. Updated 10 ...