A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas
Recruiting · NCT04104776 · Interventional (participants receive a specific treatment) · Lead sponsor: Novartis Pharmaceuticals
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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.
Who can take part
Age range
18 Years and older
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 1, Phase 2
Study type
Interventional (participants receive a specific treatment)
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
Where it is running
60 locations listed across 13 US states.
- H. Lee Moffitt Cancer Center & Research Institute - Tampa, Florida, United States
- H. Lee Moffitt Cancer Center & Research Institute - Tampa, Florida, United States
- Winship Cancer Institute of Emory University - Atlanta, Georgia, United States
- Winship Cancer Institute of Emory University - Atlanta, Georgia, United States
- University of Chicago Medical Center - Chicago, Illinois, United States
- University of Chicago Medical Center - Chicago, Illinois, United States
- Loyola University Medical Center - Maywood, Illinois, United States
- Loyola University Medical Center - Maywood, Illinois, United States
- University of Maryland Greenebaum Cancer Center - Baltimore, Maryland, United States
- University of Maryland Greenebaum Cancer Center - Baltimore, Maryland, United States
- Massachusetts General Hospital - Boston, Massachusetts, United States
- Dana Farber Cancer Institute - Boston, Massachusetts, United States
- Massachusetts General Hospital - Boston, Massachusetts, United States
- Dana Farber Cancer Institute - Boston, Massachusetts, United States
- University of Michigan Hospitals - Ann Arbor, Michigan, United States
- University of Michigan Hospitals - Ann Arbor, Michigan, United States
- South Texas Accelerated Research Therapeutics (START) - Midwest Location - Grand Rapids, Michigan, United States
- South Texas Accelerated Research Therapeutics (START) - Midwest Location - Grand Rapids, Michigan, United States
- Hackensack University Medical Center - Hackensack, New Jersey, United States
- Hackensack University Medical Center - Hackensack, New Jersey, United States
- Roswell Park Cancer Institute - Buffalo, New York, United States
- Roswell Park Cancer Institute - Buffalo, New York, United States
- Laura and Isaac Perlmutter Cancer Center at NYU Langone - New York, New York, United States
- Memorial Sloan Kettering Cancer Center - NYC - New York, New York, United States
- Weill Medical College of Cornell University - New York, New York, United States
- Laura and Isaac Perlmutter Cancer Center at NYU Langone - New York, New York, United States
- Memorial Sloan Kettering Cancer Center - NYC - New York, New York, United States
- Weill Medical College of Cornell University - New York, New York, United States
- University of Rochester Medical Center, James P. Wilmot Cancer Center - Rochester, New York, United States
- University of Rochester Medical Center, James P. Wilmot Cancer Center - Rochester, New York, United States
- Montefiore Medical Center, Montefiore Medical Center Laboratories - The Bronx, New York, United States
- Montefiore Medical Center, Montefiore Medical Center Laboratories - The Bronx, New York, United States
- University of Cincinnati Medical Center - Cincinnati, Ohio, United States
- University of Cincinnati Medical Center - Cincinnati, Ohio, United States
- Abramson Cancer Center of the University of Pennsylvania - Philadelphia, Pennsylvania, United States
- Abramson Cancer Center of the University of Pennsylvania - Philadelphia, Pennsylvania, United States
- South Texas Accelerated Research Therapeutics - San Antonio, Texas, United States
- South Texas Accelerated Research Therapeutics - San Antonio, Texas, United States
- University of Virginia Health System - Charlottesville, Virginia, United States
- University of Virginia Health System - Charlottesville, Virginia, United States
- Swedish Cancer Institute - Seattle, Washington, United States
- Fred Hutchinson Cancer Center - Seattle, Washington, United States
- Swedish Cancer Institute - Seattle, Washington, United States
- Fred Hutchinson Cancer Center - Seattle, Washington, United States
- University Hospital Vall d'Hebron - Barcelona, Spain
- Hospital Clinic of Barcelona - Barcelona, Spain
- University Hospital Vall d'Hebron - Barcelona, Spain
- Hospital Clinic of Barcelona - Barcelona, Spain
- Royal United Hospital, Department of Oncology/Hematology - Bath, United Kingdom
- Royal United Hospital, Department of Oncology/Hematology - Bath, United Kingdom
- Irccs University Hospital of Bologna - Bologna, Italy
- Irccs University Hospital of Bologna - Bologna, Italy
- CHU Bordeaux Hopital Saint Andre - Bordeaux, France
- CLCC Institut Bergonie - Bordeaux, France
- CHU Bordeaux Hopital Saint Andre - Bordeaux, France
- CLCC Institut Bergonie - Bordeaux, France
- Keimyung University - Dongsan Medical Center - Daegu, South Korea
- Keimyung University - Dongsan Medical Center - Daegu, South Korea
- University Teaching Centre, Early Clinical Trials Unit - Gdansk, Poland
- University Teaching Centre, Early Clinical Trials Unit - Gdansk, Poland
Showing 60 of 160 listed sites. See the official record for the complete list.
Read the full protocol, contacts and eligibility on ClinicalTrials.gov →