A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas

NCT04104776 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: CDZR123A02101CPI-0209-012023-508002-20-00
• Study Type: interventional
• Target: 300
• Locations: 7 countries
• Sites: 80

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; Mesothelioma, Malignant; Prostatic Neoplasms, Castration-Resistant; Endometrial Cancer; Ovarian Clear Cell Carcinoma; Metastatic Castration-resistant Prostate Cancer; Lymphoma, T-Cell

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)

Outcome Measures

Primary Outcomes (4)

• Tulmimetostat Monotherapy Phase 1: Frequency of Dose-limiting toxicities (DLTs)

  The maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of Tulmimetostat as monotherapy in patients with advanced tumors.

  DLTs assessed during Cycle 1 (cycle = 28 days)

• Tulmimetostat Monotherapy Phase 2: Overall response rate (ORR)

  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

  Up to 30 months

• Cohort M8 Part 1: Frequency of Dose-limiting toxicities (DLTs)

  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.

  DLTs assessed during Cycle 1 (cycle = 28 days)

• Cohort M8 Part 2: Prostate-Specific Antigen 50 (PSA50) Response

  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

  Up to 30 months

Secondary Outcomes (19)

• Tulmimetostat Monotherapy (Phase 1 & 2) and Cohort M8 (Parts 1 & 2): Incidence Rate of Adverse Events (AEs)

  Up to 18 months

• Tulmimetostat Monotherapy (Phase 1 & 2), Cohort M7 and Cohort M8 (Parts 1 & 2): Maximum observed plasma concentration (Cmax)

  Up to 18 months

• Tulmimetostat Monotherapy (Phase 1 & 2), Cohort M7 and Cohort M8 (Parts 1 & 2): Time of maximum observed plasma concentration (Tmax)

  Up to 18 months

• Tulmimetostat Monotherapy (Phase 1 & 2), Cohort M7 and Cohort M8 (Parts 1 & 2): Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-last)

  Up to 18 months

• Tulmimetostat Monotherapy (Phase 1 & 2), Cohort M7 and Cohort M8 (Parts 1 & 2): Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-Inf)

  Up to 18 months

Study Arms (10)

Phase 1

EXPERIMENTAL

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

Drug: Tulmimetostat

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

EXPERIMENTAL

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.

Drug: Tulmimetostat

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

EXPERIMENTAL

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.

Drug: Tulmimetostat

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

EXPERIMENTAL

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.

Drug: Tulmimetostat

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

EXPERIMENTAL

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.

Drug: Tulmimetostat

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

EXPERIMENTAL

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.

Drug: Tulmimetostat

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

EXPERIMENTAL

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.

Drug: Tulmimetostat

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

EXPERIMENTAL

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.

Drug: Tulmimetostat

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

EXPERIMENTAL

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

Drug: Tulmimetostat

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

EXPERIMENTAL

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.

Drug: Tulmimetostat; Drug: Enzalutamide

Interventions

Tulmimetostat DRUG

Tulmimetostat dosed once per day orally in 28 day cycles

Also known as: DZR123

Cohort M8 - Part 1 (Tulmimetostat + enzalutamide in mCRPC); Cohort M8 - Part 2 (Tulmimetostat + enzalutamide in mCRPC); Phase 1; Phase 2 - Cohort M1 (Advanced/metastatic solid tumors or urothelial carcinoma with ARID1A mutation); Phase 2 - Cohort M2 (Ovarian clear cell carcinoma with ARID1A mutation); Phase 2 - Cohort M3 (Endometrial carcinoma with ARID1A mutation); Phase 2 - Cohort M4 (Relapsed/refractory lymphoma (PTCL or DLBCL)); Phase 2 - Cohort M5 (Malignant mesothelioma with BAP1 loss); Phase 2 - Cohort M6 (Metastatic castration-resistant prostate cancer (mCRPC)); Phase 2 - Cohort M7 (Food effect in ARID1A wildtype endometrial carcinoma)

Enzalutamide DRUG

Enzalutamide dosed once per day orally in 28 day cycles

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

Eligibility Criteria

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

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (80)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

WITHDRAWN

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322-1013, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Loyola University Medical Center

Maywood, Illinois, 60153, United States

WITHDRAWN

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

WITHDRAWN

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5450, United States

COMPLETED

University of Michigan Hospitals

Ann Arbor, Michigan, 48109, United States

WITHDRAWN

South Texas Accelerated Research Therapeutics (START) - Midwest Location

Grand Rapids, Michigan, 49546, United States

ACTIVE NOT RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

COMPLETED

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

WITHDRAWN

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

COMPLETED

Memorial Sloan Kettering Cancer Center - NYC

New York, New York, 10065, United States

WITHDRAWN

Weill Medical College of Cornell University

New York, New York, 10065, United States

WITHDRAWN

University of Rochester Medical Center, James P. Wilmot Cancer Center

Rochester, New York, 14642, United States

WITHDRAWN

Montefiore Medical Center, Montefiore Medical Center Laboratories

The Bronx, New York, 10467-2490, United States

WITHDRAWN

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

WITHDRAWN

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

COMPLETED

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109-1023, United States

RECRUITING

CHU Bordeaux Hopital Saint Andre

Bordeaux, 33000, France

WITHDRAWN

CLCC Institut Bergonie

Bordeaux, 33000, France

RECRUITING

Centre Oscar Lambret

Lille, 59000, France

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

CHU Nantes Hopital Hotel Dieu

Nantes, 44093 Cedex 1, France

RECRUITING

CHU Nantes Hopital Nord Laennec

Saint-Herblain, 44800, France

RECRUITING

Hopital Hautepierre

Strasbourg, 67098, France

RECRUITING

Gustave Roussy

Villejuif, 94805 Cedex, France

RECRUITING

Irccs University Hospital of Bologna

Bologna, 40138, Italy

COMPLETED

National Cancer Institute, IRCCS

Milan, 20133, Italy

RECRUITING

National Cancer Institute, IRCCS

Milan, 20133, Italy

WITHDRAWN

European Institute of Oncology (IEO), IRCCS

Milan, 20141, Italy

COMPLETED

European Institute of Oncology (IEO), IRCCS

Milan, 20141, Italy

RECRUITING

Humanitas San Pio X

Milan, 20159, Italy

RECRUITING

University Polyclinic Foundation "Agostino Gemelli" - IRCCS

Roma, 00168, Italy

RECRUITING

Gruppo Humanitas - Humanitas Research Hospital - Cancer Center

Rozzano, 20089, Italy

RECRUITING

University Teaching Centre, Early Clinical Trials Unit

Gdansk, 80-214, Poland

RECRUITING

Pratia MCM Krakow

Krakow, 30-510, Poland

WITHDRAWN

Polish Mother's Memorial Hospital-Research Institute

Lodz, 93-338, Poland

WITHDRAWN

Pratia - Poznan

Poznan, 60-192, Poland

COMPLETED

University Teaching Hospital in Poznan, Department of Gynecologic Oncology

Poznan, 60-569, Poland

RECRUITING

Maria Sklodowska-Curie - National Research Institute of Oncology

Warsaw, 02-781, Poland

COMPLETED

Keimyung University - Dongsan Medical Center

Daegu, 42601, South Korea

WITHDRAWN

National Cancer Center

Goyang-si, 10408, South Korea

COMPLETED

Gachon University Gil Medical Center

Incheon, 21565, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Gangnam Severance Hospital

Seoul, 06273, South Korea

RECRUITING

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

WITHDRAWN

University Hospital Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

RECRUITING

University Hospital of Girona Dr. Josep Trueta

Girona, 17007, Spain

RECRUITING

Catalan Institute of Oncology, Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08908, Spain

WITHDRAWN

University Clinic of Navarra - Madrid

Madrid, 28027, Spain

RECRUITING

University Hospital Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

University Hospital Clinical San Carlos, Department of Medical Oncology

Madrid, 28040, Spain

RECRUITING

University Hospital Foundation Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

University Hospital 12 de Octubre

Madrid, 28041, Spain

COMPLETED

University Hospital Quiron Madrid

Madrid, 28223, Spain

RECRUITING

University Hospital Puerta de Hierro Majadahonda

Majadahonda, 28222, Spain

RECRUITING

University Hospital Son Espases

Palma, 07120, Spain

RECRUITING

University Clinic of Navarra - Pamplona

Pamplona, 31008, Spain

RECRUITING

Parc Tauli Health Corporation

Sabadell, 08208, Spain

RECRUITING

University Clinical Hospital of Salamanca

Salamanca, 37007, Spain

COMPLETED

University Hospital Complex of Santiago (CHUS)

Santiago de Compostela, 15706, Spain

RECRUITING

University Hospital Virgen del Rocio (HUVR)

Seville, 41013, Spain

RECRUITING

Valencia Oncology Institute (IVO)

Valencia, 46009, Spain

RECRUITING

University and Polytechnic Hospital La Fe

Valencia, 46026, Spain

RECRUITING

Royal United Hospital, Department of Oncology/Hematology

Bath, BA1 3NG, United Kingdom

WITHDRAWN

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

RECRUITING

Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

WITHDRAWN

Imperial College Healthcare NHS Trust

London, SW7 2AZ, United Kingdom

WITHDRAWN

The Christie NHS Foundation Trust, Department of Medical Oncology

Manchester, M20 4BX, United Kingdom

COMPLETED

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

WITHDRAWN

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

WITHDRAWN

Royal Marsden Hospital - Sutton

Sutton, SM2 5PT, United Kingdom

COMPLETED

Musgrove Park Hospital

Taunton, TA1 5DA, United Kingdom

COMPLETED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Mesothelioma, Malignant; Prostatic Neoplasms, Castration-Resistant; Endometrial Neoplasms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Site; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

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

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

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

Study Record Dates

• First Submitted: September 23, 2019
• First Posted: September 26, 2019
• Study Start: September 18, 2019
• Primary Completion (Estimated): February 27, 2030
• Study Completion (Estimated): February 27, 2030
• Last Updated: August 19, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

PL (6); US (22); ES (19); IT (8); GB (9); FR (8); KR (8)