Advanced Solid TumorDiffuse Large B Cell LymphomaLymphoma, T-CellMesothelioma, MalignantProstatic Neoplasms, Castration-ResistantEndometrial CancerOvarian Clear Cell CarcinomaMetastatic Castration-resistant Prostate Cancer
Investigational drug(s) / intervention(s)
TulmimetostatEnzalutamide
Tulmimetostat: Tulmimetostat dosed once per day orally in 28 day cycles
Enzalutamide: Enzalutamide dosed once per day orally in 28 day cycles
Study summary
The purpose of this open-label, first-in-human (FIH) trial is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of DZR123 (Tulmimetostat, CPI-0209), both as monotherapy and in combination with enzalutamide, in patients with advanced solid tumors and lymphomas.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria:
All Patients:
* Adults aged ≥18 years with life expectancy ≥12 weeks
* ECOG performance status 0-1
* Adequate recovery from prior therapy-related toxicities (Grade ≤1, with exceptions)
* Adequate bone marrow, renal, and hepatic function per protocol-defined thresholds
* Willingness to provide tumor tissue and blood samples for biomarker analyses
* Agreement to protocol-specified contraception requirements
* Signed informed consent prior to study procedures
Disease-Specific Inclusion Criteria:
Phase 1 (Dose Escalation):
* Histologically or cytologically confirmed locally advanced or metastatic solid tumors or lymphoma
* Disease refractory to standard therapy or with no available effective standard treatment
* For prostate cancer: castrate testosterone levels maintained throughout the study
Phase 2 (Disease-Specific Cohorts):
* M1: ARID1A mutant urothelial carcinoma or other ARID1A mutant solid tumors (with cohort specific prior therapy and RECIST 1.1 measurable disease requirements)
* M2: ARID1A mutant ovarian clear cell carcinoma after prior platinum-based therapy (and bevacizumab unless contraindicated)
* M3: ARID1A mutant recurrent/metastatic endometrial carcinoma after platinum therapy and appropriate immunotherapy
* M4: Relapsed/refractory peripheral T cell lymphoma or diffuse large B cell lymphoma, transplant-ineligible, with measurable disease
* M5: Relapsed/refractory pleural or peritoneal mesothelioma with documented BAP1 loss
* M6: Metastatic castration-resistant prostate cancer (mCRPC) with documented progression after AR targeted therapy and taxane chemotherapy
* M7: ARID1A wild type endometrial carcinoma (exploratory food-effect cohort)
* M8: mCRPC treated with DZR123 in combination with enzalutamide, with cohort specific requirements for prior androgen receptor pathway inhibitor and chemotherapy exposure
Key Exclusion Criteria:
All Patients:
Medical Conditions:
* Prior solid organ or allogeneic hematopoietic cell transplant
* Active or untreated symptomatic CNS metastases (with limited exceptions)
* Clinically significant cardiovascular disease, including uncontrolled arrhythmias or prolonged QTc
* Active interstitial lung disease or pneumonitis
* Uncontrolled infections or significant gastrointestinal disorders affecting absorption
* Active HIV or hepatitis B/C infection
* Concurrent malignancy requiring active treatment (with protocol-defined exceptions)
* Pregnancy, breastfeeding, or inability to comply with protocol requirements
Prior or Concomitant Therapy:
* Recent anticancer therapy within protocol-defined washout periods
* Prior EZH2 inhibitor treatment
* Recent radiation or liver-directed therapies outside allowed windows
* Use of strong CYP3A4/5 inhibitors or inducers
Additional Cohort-Specific Exclusions:
* M6 (mCRPC): Bone-only disease, unstable bone lesions, PSA-lowering herbal products, recent prohibited prostate cancer therapies
* M8 (Combination): PSA-only disease, prior investigational androgen receptor pathway inhibitors, significant seizure risk, extensive prior bone marrow irradiation, active inflammatory gastrointestinal disease
Primary outcome measure(s)
Tulmimetostat Monotherapy Phase 1: Frequency of Dose-limiting toxicities (DLTs) — DLTs assessed during Cycle 1 (cycle = 28 days) The maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of Tulmimetostat as monotherapy in patients with advanced tumors.
Tulmimetostat Monotherapy Phase 2: Overall response rate (ORR) — Up to 30 months ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) based on RECIST 1.1 or applicable response criteria
Cohort M8 Part 1: Frequency of Dose-limiting toxicities (DLTs) — DLTs assessed during Cycle 1 (cycle = 28 days) The maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of Tulmimetostat in combination with enzalutamide in patients with castration-resistant prostate cancer (mCRPC) with measurable soft tissue disease.
Cohort M8 Part 2: Prostate-Specific Antigen 50 (PSA50) Response — Up to 30 months Prostate-Specific Antigen 50 (PSA50) is defined as a ≥ 50% decrease in PSA levels from baseline at any timepoint, confirmed by a second PSA measurement ≥ 3 weeks without any PSA progression in between
Trial sites (80)
Facility
City
Region
Status
H. Lee Moffitt Cancer Center & Research Institute
Tampa
Florida
Withdrawn
Winship Cancer Institute of Emory University
Atlanta
Georgia
Recruiting
University of Chicago Medical Center
Chicago
Illinois
Recruiting
Loyola University Medical Center
Maywood
Illinois
Withdrawn
University of Maryland Greenebaum Cancer Center
Baltimore
Maryland
Withdrawn
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana Farber Cancer Institute
Boston
Massachusetts
Completed
University of Michigan Hospitals
Ann Arbor
Michigan
Withdrawn
South Texas Accelerated Research Therapeutics (START) - Midwest Location
Grand Rapids
Michigan
Active Not Recruiting
Hackensack University Medical Center
Hackensack
New Jersey
Completed
Roswell Park Cancer Institute
Buffalo
New York
Withdrawn
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York
New York
Completed
Memorial Sloan Kettering Cancer Center - NYC
New York
New York
Withdrawn
Weill Medical College of Cornell University
New York
New York
Withdrawn
University of Rochester Medical Center, James P. Wilmot Cancer Center
Rochester
New York
Withdrawn
Montefiore Medical Center, Montefiore Medical Center Laboratories
The Bronx
New York
Withdrawn
University of Cincinnati Medical Center
Cincinnati
Ohio
Withdrawn
Abramson Cancer Center of the University of Pennsylvania
Philadelphia
Pennsylvania
Recruiting
South Texas Accelerated Research Therapeutics
San Antonio
Texas
Completed
University of Virginia Health System
Charlottesville
Virginia
Recruiting
Swedish Cancer Institute
Seattle
Washington
Recruiting
Fred Hutchinson Cancer Center
Seattle
Washington
Recruiting
CHU Bordeaux Hopital Saint Andre
Bordeaux
France
Withdrawn
CLCC Institut Bergonie
Bordeaux
France
Recruiting
Centre Oscar Lambret
Lille
France
Recruiting
Centre Leon Berard
Lyon
France
Recruiting
CHU Nantes Hopital Hotel Dieu
Nantes
France
Recruiting
CHU Nantes Hopital Nord Laennec
Saint-Herblain
France
Recruiting
Hopital Hautepierre
Strasbourg
France
Recruiting
Gustave Roussy
Villejuif
France
Recruiting
Irccs University Hospital of Bologna
Bologna
Italy
Completed
National Cancer Institute, IRCCS
Milan
Italy
Recruiting
National Cancer Institute, IRCCS
Milan
Italy
Withdrawn
European Institute of Oncology (IEO), IRCCS
Milan
Italy
Completed
European Institute of Oncology (IEO), IRCCS
Milan
Italy
Recruiting
Humanitas San Pio X
Milan
Italy
Recruiting
University Polyclinic Foundation "Agostino Gemelli" - IRCCS
Roma
Italy
Recruiting
Gruppo Humanitas - Humanitas Research Hospital - Cancer Center
Rozzano
Italy
Recruiting
University Teaching Centre, Early Clinical Trials Unit
Gdansk
Poland
Recruiting
Pratia MCM Krakow
Krakow
Poland
Withdrawn
+ 40 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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