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: 275
• Locations: 7 countries
• Sites: 60

Brief Summary

The purpose of this open-label, first-in-human (FIH) trial is to evaluate the safety, tolerability, and preliminary clinical activity of Tulmimetostat as a monotherapy 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; Endometrial Cancer; Ovarian Clear Cell Carcinoma; Metastatic Castration-resistant Prostate Cancer

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: 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) per Investigator assessment based on Prostate Cancer Clinical Trials Working Group 3 (PCWG3)

  Up to 30 months

Secondary Outcomes (64)

• Tulmimetostat Monotherapy Phase 1: Incidence Rate of AEs

  Up to 18 months

• Tulmimetostat Monotherapy Phase 1: Maximum observed plasma concentration (Cmax)

  Up to 18 months

• Tulmimetostat Monotherapy Phase 1: Time of maximum observed plasma concentration (Tmax)

  Up to 18 months

• Tulmimetostat Monotherapy Phase 1: 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: 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

Tulmimetostat will be dosed once per day orally in patients with advanced tumors.

Drug: Tulmimetostat

Phase 2 Cohort M1

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in 28 day cycles. • Cohort M1: patients with urothelial carcinoma or other advanced/metastatic solid tumors (with known ARID1A mutation)

Drug: Tulmimetostat

Phase 2 Cohort M2

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in 28 day cycles. • Cohort M2 patients with ovarian clear cell carcinoma (with known ARID1A mutation)

Drug: Tulmimetostat

Phase 2 Cohort M3

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in 28 day cycles. • Cohort M3 patients with endometrial carcinoma (with known ARID1A mutation)

Drug: Tulmimetostat

Phase 2 Cohort M4

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in 28 day cycles. • Cohort M4 patients with peripheral T-cell lymphoma (PTCL) and patients with diffuse large B-cell lymphoma (DLBCL), including patients with documented germinal center B cell like diffuse large B-cell lymphoma (GCB-DLBCL) with at least 1 Enhancer of Zeste Homolog 2 (EZH2) hotspot mutation

Drug: Tulmimetostat

Phase 2 Cohort M5

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in 28 day cycles. • Cohort M5 patients with relapsed or refractory malignant pleural or peritoneal mesothelioma with known BAP1 loss

Drug: Tulmimetostat

Phase 2 Cohort M6

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in 28 day cycles. • Cohort M6 patients with castration-resistant prostate cancer (mCRPC) with measurable soft tissue disease

Drug: Tulmimetostat

Phase 2 Cohort M7

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in 28 day cycles. • Cohort M7 food effect in patients with ARID1A wildtype (ARID1A WT) endometrial carcinoma

Drug: Tulmimetostat

Phase 1 Cohort M8

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in combination with enzalutamide Cohort M8 patients with castration-resistant prostate cancer (mCRPC).

Drug: Tulmimetostat

Phase 2 Cohort M8

EXPERIMENTAL

Tulmimetostat will be dosed once per day orally in 28-day cycles in combination with enzalutamide. • Cohort M8 patients with castration-resistant prostate cancer (mCRPC).

Drug: Tulmimetostat; Drug: Enzalutamide

Interventions

Tulmimetostat DRUG

Tulmimetostat dosed once per day orally in 28 day cycles

Also known as: DZR123

Phase 1; Phase 1 Cohort M8; Phase 2 Cohort M1; Phase 2 Cohort M2; Phase 2 Cohort M3; Phase 2 Cohort M4; Phase 2 Cohort M5; Phase 2 Cohort M6; Phase 2 Cohort M7; Phase 2 Cohort M8

Enzalutamide DRUG

Enzalutamide dosed once per day orally in 28 day cycles

Phase 2 Cohort M8

Eligibility Criteria

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

You may qualify if:

• Eligible Phase 1 patients are adults who have a confirmed locally advanced or metastatic tumors (solid tumors or lymphoma) that have relapsed following standard therapy or progressed through standard therapy or who have a disease for which no standard effective therapy exists.
• Eligible Phase 2 patients in cohorts M1 to M3 are adults who are known to have the ARID1A mutation by next-generation sequencing (NGS) testing; have measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 and who have confirmed relapsed urothelial or other advanced/metastatic solid tumors (M1), ovarian clear cell carcinoma (M2), or endometrial carcinoma (M3).
• Eligible Phase 2 patients in Cohort M4 are adults who have either relapsed or refractory PTCL (at least 10 patients) or DLBCL (up to 10 patients), including patients with documented GCB DLBCL with EZH2 hotspot mutation. Patients with PTCL must have at least 1 prior line of therapy and patients with DLBCL must have at least 2 prior lines of standard therapy; and are not considered candidates to receive CAR-T or ASCT therapy.
• Eligible Phase 2 patients in Cohort M5 are adults who are known to the have the BAP1 loss, have malignant pleural or peritoneal mesothelioma, and have progressed on at least 1 prior line of active therapy.
• Eligible Phase 2 patients in Cohort M6 are adults who have mCRPC with measurable soft tissue disease with CT scan as defined by PCWG3 criteria, have baseline testosterone levels ≤ 50 ng/dL (≤ 2.0 nM) and have surgical or ongoing medical castration and who have progressed on at least 1 androgen-receptor signaling inhibitor and at least 1 taxane-based chemotherapy (cabazitaxel, France only).
• Eligible Phase 2 patients in Cohort M7 are adults with recurrent, advanced ARID1A WT endometrial carcinoma confirmed by NGS testing and have measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 Patients will be enrolled with maximum up to 2 prior lines of systemic therapy for treating endometrial carcinoma that must include at least one treatment line with systemic platinum-based chemotherapy in advanced/ recurrent disease setting, and anti-programmed cell death protein 1 (PD-1)/ anti-programmed death-ligand 1 (PD-L1) therapy, either in combination or separately, unless these are contraindicated or are not locally accessible.
• Eligible Part 1 and Part 2 patients in Cohort M8 are adults who have mCRPC with measurable soft tissue disease as per PCWG3 criteria, have baseline testosterone levels ≤ 50 ng/dL (≤ 2.0 nM), have surgical or ongoing medical castration or hormone sensitive prostate cancer (HSPC) disease stage. In addition, Eligible part 1 patients in Cohort M8 may have received abiraterone treatment in mCRPC while eligible part 2 patients in Cohort M8 must have received abiraterone treatment in mCRPC. In addition, only for M8 Part 1: Patients may have received no more than one previous regimen of taxane-based chemotherapy in mCRPC or HSPC setting. For M8 Part 2: Patients may have received no more than one previous regimen of taxane-based chemotherapy in HSPC setting. Patients for both M8 Part 1 and M8 Part 2 must have evidence of prostate cancer progression (per PCWG3) and must have ongoing ADT (androgen deprivation therapy) with a GnRH analogue, antagonist or bilateral orchiectomy (i.e., surgical or medical castration).
• All patients will have Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 and adequate organ function.

You may not qualify if:

• Medical Conditions
• Previous solid organ or allogeneic hematopoietic cell transplantation (HCT).
• Known symptomatic untreated brain metastases. Patients with central nervous system (CNS) metastases must have stable neurologic status following local therapy for at least 4 weeks on a stable or decreasing dose of steroids (≤ 10 mg daily prednisone or equivalent). Patients in the M4 lymphoma cohort are excluded if they have known CNS involvement by lymphoma.
• Clinically significant cardiovascular disease, including:
• Myocardial infarction or stroke within 3 months (6 months for M8 cohort) prior to Day 1 of treatment.
• Unstable angina within 3 months (6 months for M8 cohort) prior to Day 1 of treatment.
• Congestive heart failure or cardiomyopathy with New York Heart Association (NYHA) Class 3 or 4.
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes).
• Uncontrolled hypertension despite 2 concomitant antihypertensive therapies.
• For Cohorts M1-M6: QT interval corrected by the Fridericia correction formula (QTcF) \> 480 msec on the Screening ECG.
• For Cohorts M7 and M8: QTcF interval ≥ 450 msec at screening.
• Major surgery within 4 weeks before starting study drug or not recovered from any effects of prior major surgery (uncomplicated central line placement or fine needle aspirate are not considered major surgery).
• Gastrointestinal disorders that may significantly interfere with the absorption of the study medication, such as ulcerative colitis, malabsorption syndrome, refractory nausea and vomiting, biliary shunt, significant bowel resection.
• Uncontrolled active infection requiring intravenous antibiotic, antiviral, or antifungal medications within 14 days before the first dose of study drug. Controlled infections on concurrent antimicrobial agents and antimicrobial prophylaxis per institutional guidelines are acceptable.
• Suspected pneumonitis or interstitial lung disease (confirmed by radiography or CT) or a history of these conditions.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (60)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322-1013, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

University of Maryland - Marlene and Stewart 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

RECRUITING

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

WITHDRAWN

South Texas Accelerated Research Therapeutics (Start) - Midwest Location

Grand Rapids, Michigan, 49546, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

RECRUITING

Weill Medical College of Cornell University

New York, New York, 10065, United States

WITHDRAWN

Montefiore Einstein Center for Cancer Care

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

RECRUITING

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

RECRUITING

Fred Hutchinson Cancer

Seattle, Washington, 98109-1023, United States

RECRUITING

Bergonie Institute

Bordeaux, 33000, France

RECRUITING

Oscar Lambret Center

Lille, 59020, France

RECRUITING

Leon Berard Center

Lyon, 69373, France

RECRUITING

Nantes University Hospital Center - Hotel Dieu Hospital (Satellite)

Nantes, 44093, France

RECRUITING

Nantes University Hospital Center - Hotel Dieu Hospital

Nantes, 44093, France

RECRUITING

Nord Laennec Hospital

Saint-Herblain, 44800, France

RECRUITING

Strasbourg Europe Institut of Cancerology

Strasbourg, 67200, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Irccs University Hospital of Bologna

Bologna, 40138, Italy

RECRUITING

National Cancer Institute, IRCCS

Milan, 20133, Italy

RECRUITING

European Institute of Oncology (IEO), IRCCS

Milan, 20141, Italy

RECRUITING

University Polyclinic Foundation "Agostino Gemelli" - IRCCS

Rome, 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

Polish Mother's Memorial Hospital-Research Institute

Lodz, 93-338, Poland

RECRUITING

University Teaching Hospital in Poznan, Department of Gynecologic Oncology

Poznan, 60-569, Poland

RECRUITING

Medical Center Pratia Poznan

Skorzewo, 60-185, Poland

RECRUITING

Maria Sklodowska-Curie - National Research Institute of Oncology

Warsaw, 02-781, Poland

RECRUITING

Keimyung University - Dongsan Medical Center

Daegu, 42601, South Korea

RECRUITING

National Cancer Center

Goyang-si, 10408, South Korea

RECRUITING

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

University Hospital Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

University Hospital of Girona Dr. Josep Trueta

Girona, 17007, Spain

RECRUITING

University Clinic of Navarra - Madrid

Madrid, 28027, Spain

RECRUITING

University Hospital 12 de Octubre

Madrid, 28041, Spain

RECRUITING

University Hospital Quiron Madrid

Madrid, 28223, Spain

RECRUITING

University Hospital Son Espases

Palma de Mallorca, 07120, Spain

RECRUITING

University Clinic of Navarra - Pamplona

Pamplona, 31008, Spain

RECRUITING

University Clinical Hospital of Salamanca

Salamanca, 37007, Spain

RECRUITING

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

Royal United Hospital

Bath, BA1 3NG, United Kingdom

RECRUITING

University Hospitals of Leicester NHS Trust

Leicester, LE5 4PW, United Kingdom

RECRUITING

Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, SW7 2AZ, United Kingdom

RECRUITING

The Christie NHS Foundation Trust, Department of Medical Oncology

Manchester, M20 4BX, United Kingdom

RECRUITING

Royal Marsden Hospital - Sutton

Sutton, SM2 5PT, United Kingdom

RECRUITING

Musgrove Park Hospital

Taunton, TA1 5DA, United Kingdom

RECRUITING

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: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

PL (5); US (17); ES (11); IT (5); GB (7); FR (8); KR (7)