Recruiting
Phase 1
Phase 2

CPI-0209

Sponsor:

Novartis Pharmaceuticals

Code:

NCT04104776

Conditions

Advanced Solid Tumor

Diffuse Large B Cell Lymphoma

Lymphoma, T-Cell

Mesothelioma, Malignant

Prostatic Neoplasms, Castration-Resistant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Tulmimetostat

Enzalutamide

Study Details

Brief 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.

Conditions

Advanced Solid Tumor

Diffuse Large B Cell Lymphoma

Lymphoma, T-Cell

Mesothelioma, Malignant

Prostatic Neoplasms, Castration-Resistant

Study ID

NCT04104776

Start date

Sep 18, 2019

Status verified date

Aug, 2026

Completion date

Feb 27, 2030

Anticipated

Primary completion date

Feb 27, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

300 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1

Eligible participants with advanced tumors will receive escalating doses of Tulmimetostat once per day orally.

experimental: Phase 2 - Cohort M1 (Advanced/metastatic solid tumors or urothelial carcinoma with ARID1A mutation)

Eligible participants with advanced/metastatic solid tumors (excluding ovarian clear cell and endometrial carcinoma) or urothelial carcinoma, confirmed to have ARID1A mutations will receive oral Tulmimetostat once daily in 28-day treatment cycles.

experimental: Phase 2 - Cohort M2 (Ovarian clear cell carcinoma with ARID1A mutation)

Eligible participants with advanced ovarian clear cell carcinoma, confirmed to have ARID1A mutations, who have received prior platinum-based chemotherapy will receive oral Tulmimetostat once daily in 28-day treatment cycles.

experimental: Phase 2 - Cohort M3 (Endometrial carcinoma with ARID1A mutation)

Eligible participants with recurrent, metastatic, or unresectable endometrial carcinoma, confirmed to have ARID1A mutations, and prior platinum-based therapy will receive oral Tulmimetostat once daily in 28-day treatment cycles.

experimental: Phase 2 - Cohort M4 (Relapsed/refractory lymphoma (PTCL or DLBCL))

Eligible participants with relapsed or refractory peripheral T-cell lymphoma (PTCL) or diffuse large B-cell lymphoma (DLBCL), including those with EZH2 hotspot mutations will receive oral Tulmimetostat once daily in 28-day treatment cycles.

experimental: Phase 2 - Cohort M5 (Malignant mesothelioma with BAP1 loss)

Eligible participants with relapsed or refractory malignant pleural or peritoneal mesothelioma, confirmed to have BAP1 loss will receive oral Tulmimetostat once daily in 28-day treatment cycles.

experimental: Phase 2 - Cohort M6 (Metastatic castration-resistant prostate cancer (mCRPC))

Eligible participants with mCRPC, measurable soft tissue disease, and prior treatment with at least one androgen receptor signaling inhibitor and one taxane-based chemotherapy will receive oral Tulmimetostat once daily in 28-day treatment cycles.

experimental: Phase 2 - Cohort M7 (Food effect in ARID1A wildtype endometrial carcinoma)

Eligible participants with recurrent, advanced endometrial carcinoma that is ARID1A wildtype (no ARID1A mutation), to evaluate the effect of food on DZR123 pharmacokinetics will receive oral Tulmimetostat once daily in 28-day treatment cycles.

experimental: Cohort M8 - Part 1 (Tulmimetostat + enzalutamide in mCRPC)

Eligible participants with mCRPC receive DZR123 in combination with enzalutamide. Part 1 is dose escalation to determine the recommended dose.

experimental: Cohort M8 - Part 2 (Tulmimetostat + enzalutamide in mCRPC)

Eligible participants with mCRPC receive DZR123 in combination with enzalutamide. Part 2 is expansion at the selected dose to further assess safety and antitumor activity.

Interventions

Tulmimetostat

Tulmimetostat dosed once per day orally in 28 day cycles

Enzalutamide

Enzalutamide dosed once per day orally in 28 day cycles

Primary outcome measure

  • Tulmimetostat Monotherapy Phase 1: Frequency of Dose-limiting toxicities (DLTs) [ Time Frame: DLTs assessed during Cycle 1 (cycle = 28 days) ]
  • Tulmimetostat Monotherapy Phase 2: Overall response rate (ORR) [ Time Frame: Up to 30 months ]
  • Cohort M8 Part 1: Frequency of Dose-limiting toxicities (DLTs) [ Time Frame: DLTs assessed during Cycle 1 (cycle = 28 days) ]
  • Cohort M8 Part 2: Prostate-Specific Antigen 50 (PSA50) Response [ Time Frame: Up to 30 months ]

Central Contacts and Locations

Central contacts

Novartis Pharmaceuticals

1-888-669-6682novartis.email@novartis.com

Novartis Pharmaceuticals

+41613241111novartis.email@novartis.com

Locations

Winship Cancer Institute of Emory University

Recruiting

Atlanta, Georgia, United States, 30322-1013

Principal Investigator:

Beryl Manning-Geist, MD

University of Chicago Medical Center

Recruiting

Chicago, Illinois, United States, 60637

Principal Investigator:

Hedy Lee Kindler, MD

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator:

Ryan Sullivan, MD

Abramson Cancer Center of the University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Principal Investigator:

Lainie Martin, MD

University of Virginia Health System

Recruiting

Charlottesville, Virginia, United States, 22908

Principal Investigator:

Linda Duska, MD

Swedish Cancer Institute

Recruiting

Seattle, Washington, United States, 98104

Principal Investigator:

Charles Drescher, MD

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109-1023

Principal Investigator:

Kalyan Banda, MD

More Information

Sponsor

Novartis Pharmaceuticals

Last update posted

Aug 19, 2026

Last verified

Aug, 2026

Keywords

  • Tulmimetostat
  • DZR123
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, B-cell
  • Lymphoma, T-cell
  • Lymphoma, Non-Hodgkin
  • Lymphoma
  • Neoplasms by Site
  • Neoplasms by Histologic Type
  • Neoplasms
  • Lymphoproliferative Disorders
  • Lymphatic Diseases
  • Immunoproliferative Disorders
  • Immune System Diseases
  • Topoisomerase Inhibitors
  • Molecular Mechanisms of Pharmacological Action
  • Antineoplastic Agents
  • Endometrial Cancer
  • Ovarian Clear Cell Carcinoma
  • Food effect
  • Adenine-thymine (AT)-rich interactive domain-containing protein 1A (ARID1A)
  • ARID1A wildtype (ARID1A WT) endometrial carcinoma
  • Metastatic castration-resistant prostate cancer (mCRPC)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Novartis Pharmaceuticals on 2026-08-19.