Valemetostat for T-Cell Lymphoma

Recruiting at 59 trial locations

Overseen By (US sites) Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Daiichi Sankyo

Must not be taking: CYP3A inducers, Corticosteroids

Disqualifiers: Mycosis fungoides, Sézary syndrome, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 23 months

155 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will characterize the safety and clinical benefit of valemetostat tosylate in participants with relapsed/refractory peripheral T-cell lymphoma, including relapsed/refractory adult T-cell leukemia/lymphoma.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) from prior lymphoma-directed therapy before enrollment. This includes stopping systemic therapy like chemotherapy or immunomodulatory therapy at least 3 weeks or 5 half-lives of the drug, whichever is longer, before the first dose of the study drug.

What data supports the effectiveness of the drug Valemetostat for T-Cell Lymphoma?

Valemetostat has shown promising results in a phase 2 trial for treating relapsed or refractory adult T-cell leukemia/lymphoma, with an overall response rate of 48%, including complete and partial remissions. It was also approved in Japan for this condition, indicating its potential effectiveness. ^{1 2 3 4 5}

Is Valemetostat safe for humans?

Valemetostat has been tested in clinical trials and was generally well tolerated in both patients with T-cell leukemia/lymphoma and healthy subjects. Common side effects included low blood cell counts, hair loss, and changes in taste, but these were manageable. In healthy subjects, side effects were mild, and no severe treatment-related adverse events were reported. ^{1 2 3 4 6}

What makes the drug Valemetostat unique for treating T-cell lymphoma?

Valemetostat is unique because it is a selective dual inhibitor of EZH1 and EZH2, enzymes involved in cancer cell growth, and is taken orally, offering a novel approach for treating relapsed or refractory adult T-cell leukemia/lymphoma, a condition with limited treatment options. ^{1 2 3 4 7}

Research Team

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

Adults over 18 with relapsed/refractory peripheral T-cell lymphoma or adult T-cell leukemia/lymphoma, who have tried at least one systemic therapy and are ineligible for hematopoietic cell transplantation. Participants must have measurable disease and cannot have had recent major surgery or radiation, uncontrolled heart issues, prior EZH inhibitor treatment, certain other cancers within the last two years, active central nervous system involvement of lymphoma, or recent history of stem cell transplant.

Inclusion Criteria

I have a tumor that can be measured in size using a CT or MRI scan.

My condition is ALK-negative anaplastic large cell lymphoma.

I am at least 18 years old or the legal adult age in my country.

Exclusion Criteria

I have or might have long QT syndrome, or it runs in my family.

I have a heart rhythm problem that is not under control, except for stable atrial fibrillation.

My heart rate is usually below 50 beats per minute, but I have a pacemaker.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 200 mg/day valemetostat tosylate monotherapy

23 months

Cycle 1 Day 1, 8, 15 Predose; Cycle 1 Day 1 (1, 2, 4, 5 hours Postdose); Cycle 2 Day 1 Predose; Cycle 3 Day 1 to Cycle 5 Day 1 Predose (each cycle is 28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term outcomes and duration of response

56 months

Treatment Details

Interventions

• Valemetostat Tosylate

Trial Overview The trial is testing Valemetostat Tosylate's safety and effectiveness in patients with specific types of peripheral T-cell lymphomas that haven't responded to previous treatments. It focuses on those whose conditions returned after treatment or didn't improve significantly.

Participant Groups

Group I: Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/Lymphoma Experimental Treatment 1 Intervention

Participants who will receive 200 mg/day valemetostat tosylate and had an eligible adult T-cell leukemia/lymphoma subtype that was confirmed by the local pathologist/investigators and by documented positive anti-human T-cell leukemia virus type 1 (HTLV-1) antibody.

Group II: Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma Experimental Treatment 1 Intervention

Participants who will receive 200 mg/day valemetostat tosylate and had an eligible peripheral T-cell lymphoma subtype that was confirmed by independent hematopathology central review.

Valemetostat Tosylate is already approved in Japan for the following indications:

Approved in Japan as Ezharmia for:

• Adult T-cell leukemia/lymphoma
• Peripheral T-cell lymphoma

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Daiichi Sankyo, Inc.

Lead Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Findings from Research

Valemetostat, an oral inhibitor of EZH2 and EZH1, was found to be well tolerated and clinically active in patients with relapsed/refractory non-Hodgkin lymphoma during a first-in-human phase-1 trial.

In phase 1 trials with healthy Japanese participants, the new tablet formulation of valemetostat showed similar pharmacokinetics to the capsule form, but it is recommended to take the tablets in a fasted state to avoid reduced absorption and effectiveness after meals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Pharmacokinetics of Valemetostat Tablets and the Effect of Food on Valemetostat Pharmacokinetics in Healthy Subjects: Two Phase 1 Studies. Tachibana, M., Matsuki, S., Toyama, K., et al.[2023]

In a phase I study involving 32 healthy Japanese male participants, the co-administration of valemetostat with itraconazole significantly increased its peak concentration (Cmax) by 2.9-fold and overall exposure (AUCinf) by 4.2-fold, indicating a strong drug interaction.

No serious adverse events were reported, suggesting that valemetostat is safe when used with these antifungal medications, but dose adjustments are necessary when combined with strong CYP3A and P-glycoprotein inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of itraconazole and fluconazole on the pharmacokinetics of valemetostat: An open-label, phase I study in healthy subjects. Tachibana, M., Matsuki, S., Maekawa, Y., et al.[2023]

Tazemetostat (Tazverik™) is the first approved treatment specifically for adults and adolescents aged 16 years and older with locally advanced or metastatic epithelioid sarcoma, receiving accelerated approval in January 2020 in the USA.

The recommended dosage is 800 mg taken orally twice daily, and Tazemetostat is also being studied for other cancers, including diffuse large B-cell lymphoma and follicular lymphoma, indicating its potential broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tazemetostat: First Approval. Hoy, SM.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Valemetostat Tosilate: First Approval. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Pharmacokinetics of Valemetostat Tablets and the Effect of Food on Valemetostat Pharmacokinetics in Healthy Subjects: Two Phase 1 Studies. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of itraconazole and fluconazole on the pharmacokinetics of valemetostat: An open-label, phase I study in healthy subjects. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Pralatrexate pharmacology and clinical development. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Tazemetostat: First Approval. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

The emerging role of histone deacetylase inhibitors in treating T-cell lymphomas. [2021]