Valemetostat for T-Cell Lymphoma

Not currently recruiting at 69 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called valemetostat tosylate for individuals with certain types of T-cell lymphoma, a cancer affecting the immune system. The goal is to assess the safety and effectiveness of this drug for those whose cancer has returned or did not respond to previous treatments. The trial includes two groups: one for peripheral T-cell lymphoma and another for adult T-cell leukemia/lymphoma. Individuals who have tried at least one other systemic treatment for these conditions and are no longer eligible for a stem cell transplant might be suitable candidates for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that valemetostat tosylate is likely to be safe for humans?

Research has shown that valemetostat tosylate has been tested for safety in patients with relapsed or hard-to-treat T-cell lymphomas. In these studies, serious side effects occurred in 40% of patients with peripheral T-cell lymphoma and 68% of those with adult T-cell leukemia/lymphoma. While some patients experienced serious issues, others tolerated the treatment better.

Valemetostat has also been approved in Japan for treating adult T-cell leukemia/lymphoma. This approval suggests that the treatment's benefits are considered greater than the risks for this condition.

Prospective trial participants should discuss these findings with a healthcare provider. This discussion can help clarify potential risks and benefits based on individual health needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for T-cell lymphoma?

Valemetostat Tosylate is unique because it targets the EZH1 and EZH2 enzymes, which play a role in the growth of certain cancer cells. Unlike standard treatments for T-cell lymphoma, which often involve chemotherapy that can affect both cancerous and healthy cells, valemetostat offers a more targeted approach. Researchers are excited about its potential to specifically disrupt cancer cell proliferation with fewer side effects, providing a new avenue of hope for patients with relapsed or refractory forms of this disease.

What evidence suggests that valemetostat tosylate might be an effective treatment for T-cell lymphoma?

Research has shown that valemetostat tosylate can help people with difficult-to-treat T-cell lymphoma. In this trial, participants with peripheral T-cell lymphoma will receive valemetostat tosylate, which has led to lasting improvements in previous studies. For those with adult T-cell leukemia/lymphoma, who will also receive valemetostat tosylate in this trial, past research has demonstrated positive results. The drug targets specific proteins in cancer cells, helping to stop their growth. Although side effects are possible, these findings suggest valemetostat tosylate may be effective for these conditions. ^{2 3 5 6 7}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00503-5/abstract

Valemetostat for patients with relapsed or refractory ... Serious treatment-emergent adverse events were reported in 53 (40%) patients with peripheral T-cell lymphoma and 15 (68%) patients with adult T- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10651775/

An open-label, single-arm phase 2 trial of valemetostat for ... This phase 2 study assessed the efficacy and safety of the dual EZH2 and EZH1 inhibitor valemetostat in patients with R/R ATL.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04703192

Study Details | NCT04703192 | Valemetostat Tosylate (DS- ... This study will characterize the safety and clinical benefit of valemetostat tosylate in participants with relapsed/refractory peripheral T-cell lymphoma, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204524005035

Articles Valemetostat for patients with relapsed or refractory ... These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a ...

5. daiichisankyo.com daiichisankyo.com/media/press_release/detail/index_3162.html

Daiichi Sankyo Initiates Pivotal Phase 2 Trial in Japan with ... The pivotal, open-label, multi-center, single-arm phase 2 study will evaluate efficacy and safety of valemetostat as monotherapy in patients with relapsed/ ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39486433/

Valemetostat for patients with relapsed or refractory ... The primary endpoint for patients with adult T-cell leukaemia/lymphoma was the safety and tolerability of valemetostat. Safety in both cohorts was assessed ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/303/502756/Valemetostat-for-Relapsed-or-Refractory-Peripheral

Valemetostat for Relapsed or Refractory Peripheral T-Cell ... Valemetostat was approved in Japan for the Tx of R/R adult T-cell leukemia/lymphoma (ATLL) in 2022. The clinical activity of valemetostat in ...