DS-3201b for Lymphoma

Not currently recruiting at 27 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Daiichi Sankyo Co., Ltd.

Must not be taking: CYP3A inhibitors, P-gp inhibitors

Disqualifiers: CNS involvement, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, DS-3201b, for individuals with non-Hodgkin lymphoma (NHL) that has returned after treatment or isn't responding to current options. The trial consists of three parts: first, determining a safe dose; second, assessing the drug's effectiveness and gathering additional safety information; and third, examining how DS-3201b interacts with other drugs in the body. Adults with NHL who have experienced a relapse or whose disease resists standard treatments might be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but if you are part of the Drug-Drug Interaction (DDI) Cohort, you must not have taken certain medications like CYP3A inhibitors/inducers, P-gp inhibitors, midazolam, or digoxin within 14 days before starting the study.

Is there any evidence suggesting that DS-3201b is likely to be safe for humans?

Research has shown that DS-3201b, also known as valemetostat, is generally well-tolerated by patients with relapsed or refractory non-Hodgkin lymphoma. In an initial human study, the drug appeared safe, and patients handled the treatment well. However, higher doses caused some side effects, prompting researchers to test lower doses to minimize these effects. Another study found that valemetostat was safe for Japanese children and demonstrated good anti-tumor effects. While these results are promising, this is early-stage research, and ongoing studies will continue to monitor safety and tolerance closely. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphoma, which often involve chemotherapy or radiation, DS-3201b is unique because it targets specific enzymes involved in cancer cell growth—specifically, histone deacetylases (HDACs). This approach aims to stop the cancer cells from multiplying rather than just killing them outright, potentially leading to fewer side effects. Researchers are excited about DS-3201b because it offers a targeted treatment option that could be more effective and less toxic compared to traditional therapies. Additionally, by employing a dose escalation method, scientists hope to find the optimal dose that maximizes benefits while minimizing risks, which could make this treatment a game-changer for lymphoma patients.

What evidence suggests that DS-3201b might be an effective treatment for lymphoma?

Research has shown that DS-3201b, a new drug under investigation in this trial, may help treat certain types of lymphoma. In studies, 83.3% of patients with T-cell lymphomas responded well to the drug, meaning that out of six patients treated, five showed positive results. DS-3201b has also shown promise in fighting various blood cancers. These early findings suggest that DS-3201b could be effective for non-Hodgkin lymphoma, especially for patients who haven't had success with other treatments. Participants in this trial will join either a dose escalation or dose expansion phase to further examine the safety and efficacy of DS-3201b. ^{1 2 6 7 8}

Who Is on the Research Team?

Global Clinical Leader, MD

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

Adults with non-Hodgkin lymphoma whose disease has returned after remission or isn't responding to treatment may join. They must be of legal age, have good performance status (able to carry out daily activities), agree to use contraception, and provide tumor tissue samples. People with certain types of T-cell lymphoma or leukemia, CNS involvement, recent stem cell transplant, other serious diseases, pregnancy or breastfeeding are excluded.

Inclusion Criteria

If of reproductive potential, agrees to avoid harvesting ova or sperm, and to use a protocol-defined form of contraception or avoid intercourse, during and upon completion of the study, and for at least 3 months after the last dose of study drug

I am fully active or can carry out light work.

I am willing to provide tissue samples from my tumor for testing.

Exclusion Criteria

I have been diagnosed with a specific type of skin or blood cancer.

I have taken certain medications that affect liver enzymes or heart medication in the last 14 days.

I do not have any serious health or mental conditions that could worsen by joining this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Identify the recommended phase 2 dose of DS-3201b guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation.

4 weeks

Cycle 1 Day 1, Cycle 1 Day 15

Dose Expansion

Examine the safety and efficacy of DS-3201b for rare types of NHL and collect additional safety data.

4 weeks

Drug-Drug Interaction (DDI) Cohort

Evaluate the effect of DS-3201b on the pharmacokinetics of midazolam and digoxin when co-administered to patients with NHL.

4 weeks

Day -4, Cycle 1 Day 1, Cycle 1 Day 15

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• DS-3201b

Trial Overview DS-3201b is an experimental drug being tested in adults with advanced non-Hodgkin lymphoma. The study has three parts: finding a safe dose (Dose Escalation), assessing effectiveness for rare NHL types and collecting safety data (Dose Expansion), and studying how DS-3201b affects the body's handling of other drugs when taken together (DDI Cohort - US only).

How Is the Trial Designed?

Group I: Dose Expansion - DS-3201b Experimental Treatment 1 Intervention

Part 2 is a dose expansion to examine the safety and efficacy of DS-3201b.

Group II: Dose Escalation - DS-3201b Experimental Treatment 1 Intervention

Dose escalation is to identify the recommended phase 2 dose of DS-3201b guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation.

Who Is Running the Clinical Trial?

Daiichi Sankyo Co., Ltd.

Lead Sponsor

Trials

116

Recruited

49,200+

Daiichi Sankyo

Industry 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.

Industry 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

The introduction of rituximab has diminished the effectiveness of the International Prognostic Index (IPI) in predicting outcomes for patients with diffuse large B-cell lymphoma (DLBCL), as shown in a retrospective analysis of 831 patients.

The study validated the absolute lymphocyte count/revised International Prognostic Index (ALC/R-IPI) model, indicating it can still be useful for clinical trials, but highlights the need for a new prognostic model that better identifies high-risk patients in the context of modern treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic models for diffuse large B-cell lymphoma in the rituximab era: a never-ending story. Bari, A., Marcheselli, L., Sacchi, S., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.10003

Safety and efficacy of the EZH1/2 inhibitor valemetostat ... Valemetostat was safe in Japanese pediatric patients, demonstrating antitumor activity against INI1-negative tumors, such as AT/RT.

2. daiichisankyo.com daiichisankyo.com/media/press_release/detail/index_3293.html

Daiichi Sankyo Presents Phase 1 Data for EZH1/2 Dual ... An overall response rate of 83.3 percent (5 of 6 patients) was observed with DS-3201 in six evaluable patients with T-cell lymphomas, including ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02732275

NCT02732275 | DS-3201b in Participants With Lymphomas DS-3201b is an experimental drug that is being investigated in clinical research. Adults with non-Hodgkin lymphoma (NHL) may be able to join this study if ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9705507/

Valemetostat Tosilate: First Approval - PMC - PubMed Central The tumour control rate (CR + PR + SD) was 88.0% (22/25 patients). In patients who had received prior treatment with mogamulizumab, the ORR was ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S000649711984586X

First-in-Human Study of the EZH1/2 Dual Inhibitor DS ... DS-3201b is a potent inhibitor with high specificity for EZH1 and EZH2 that has demonstrated anti-tumor activity against various hematological malignancies in ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2019-00366

DS-3201b in Participants With Lymphomas - NCI DS-3201b is an experimental drug that is being investigated in clinical research. Adults with non-Hodgkin lymphoma (NHL) may be able to join this study if ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11371507/

A phase I/II study of valemetostat (DS-3201b), an EZH1/2 ... While the starting dose of valemetostat 100 mg daily was selected based on available clinical and safety data, lower doses may avert some observed toxicities, ...

8. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/full/10.1002/cpdd.1315

Safety, Tolerability, and Pharmacokinetics of Valemetostat ... In a first-in-human phase-1 trial, valemetostat capsules were well tolerated and clinically active in patients with relapsed/refractory non-Hodgkin lymphoma.