Tulmimetostat (DZR123) in Patients With Mycosis Fungoides and Sézary Syndrome

NCT05944562 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202310037
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The hypotheses of this study are that single agent DZR123 will be safe and well tolerated in patients with advanced (stage IB-IVB) mycosis fungoides (MF)/Sézary syndrome (SS) who have had at least one prior systemic therapy, and that in these patients, DZR123 will demonstrate efficacy and be worth of further study.

Conditions

Mycosis Fungoides; Sezary Syndrome; Mycosis Fungoides/Sezary Syndrome

Outcome Measures

Primary Outcomes (2)

• Frequency and grades of treatment-emergent adverse events (TEAE)

  From start of treatment through 30 days after completion of treatment (estimated to be 13 months)

• Rate of treatment discontinuation due to treatment-emergent adverse events (TEAE)

  From start of treatment through 30 days after completion of treatment (estimated to be 13 months)

Secondary Outcomes (6)

• Recommended phase II dose/maximum tolerated dose of CPI-0209

  Through completion of cycle 1 (28 days) of all dose de-escalation patients enrolled (each patient followed for 28 days)

• Overall response rate (ORR)

  At 4 months

• Time to maximum response

  Through completion of treatment (estimated to be 12 months)

• Best overall response rate

  Through completion of treatment (estimated to be 12 months)

• Complete remission rate

  Through completion of follow-up (estimated to be 36 months)

Study Arms (3)

Dose De-Escalation Cohort: Tulmimetostat (DZR123)

EXPERIMENTAL

Daily DZR123 by mouth for days 1-28 of each 28-day cycle. Dose will depend on dose level assignment of 300 mg daily, 250 mg daily, or 200 mg daily.

Dose Expansion Cohort: Tulmimetostat (DZR123) - 300 mg

EXPERIMENTAL

Daily DZR123by mouth for days 1-28 of each 28-day cycle. Dose will be the maximum-tolerated dose found during the dose de-escalation cohort which was 300 mg.

Dose Expansion Cohort: Tulmimetostat (DZR123) - 200 mg

EXPERIMENTAL

Daily DZR123 by mouth for days 1-28 of each 28-day cycle. Dose will be 200 mg as the maximum tolerated dose of 300 mg found during the initial dose expansion cohort caused numerous dose reductions.

Interventions

Tulmimetostat DRUG

Patients should take DZR123 at approximately the same time every morning in a fasted state (no food for 2 hours prior and 1 hour following DZR123 dosing). Each dose of DZR123 should be taken with a glass of water and consumed over as short a time as possible.

Also known as: DZR123

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed mycosis fungoides or Sézary syndrome, stages IB to IVB with measurable disease and/or detectable blood involvement based on the Global Response Criteria for CTCL (Olsen et al., 2022).
• Received at least one prior line of systemic therapy.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate counts and organ function as defined below:
• ANC ≥ 0.7 x 109/L, without growth factor support (filgrastim or pegfilgrastim) for at least 14 days
• Platelets ≥ 75 x 109/L, without platelet transfusion for at least 14 days
• Hemoglobin ≥ 8.0 g/dL, with or without transfusion
• Serum total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
• Creatinine clearance \> 30 mL/min by Cockcroft-Gault (using actual body weight) for patients with creatinine levels above institutional normal OR serum creatinine ≤ 1.5 x ULN
• Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression.
• The effects of DZR123 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use highly effective methods of contraception for the duration of study participation and for 183 days after the last dose of DZR123 for female patients and female partners of male patients, or for 93 days after the last dose of DZR123 for male patients and male partners of female patients. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

You may not qualify if:

• Prior treatment with an EZH2 inhibitor.
• Patients with CNS lymmphoma.
• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Those with local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, high grade superficial bladder cancer and carcinoma in situ, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to registration, asymptomatic breast cancer on adjuvant hormonal therapy diagnosed more than 2 years ago, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years are eligible.
• Currently receiving any other investigational agents. Concomitant use of another systemic therapy for MF/SS. Patients must have the following minimum wash-out from previous treatments:
• At least 8 weeks for low-dose (12 Gy or less) total skin electron beam therapy (TSEBT)
• At least 4 weeks for systemic cytotoxic anticancer agents or for tumor-targeting monoclonal antibodies (mAbs), with the exception of alemtuzumab, for which the washout is at least 16 weeks
• At least 2 weeks or 5 half-lives for systemic retinoids, interferons, vorinostat, romidepsin, and denileukin diftitox, or anticancer investigational agents that are not defined as immunotherapy,
• At least 2 weeks for local radiation therapy
• At least 1 week for topical retinoids, nitrogen mustard, or imiquimod
• Taking concomitant medication(s) or food or beverage that are strong CYP3A inducers or inhibitors within 7 days prior to the first dose of study drug.
• History of allogeneic HCT within 90 days prior to the first dose of study drug.
• Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic immunosuppressive prophylaxis or treatment.
• Previous solid organ transplant.
• Clinically significant cardiovascular disease including:

Sponsors & Collaborators

• Swim Across America: collaborator
• Washington University School of Medicine: lead
• Novartis: collaborator
• The Foundation for Barnes-Jewish Hospital: collaborator
• Daniel E. Corbin Jr. Lymphoma Fund: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Mycosis Fungoides; Sezary Syndrome

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Neha Mehta-Shah, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 13, 2023
• Study Start: January 9, 2024
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): January 31, 2029
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)