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

August 18, 2026 updated by: Novartis Pharmaceuticals

A Phase 1/2 Study of DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study consists of Phase 1 dose-escalation and Phase 2 dose-expansion cohorts designed to characterize DZR123 across multiple tumor-specific populations and to identify dose levels for further clinical development. Phase 2 includes disease-specific monotherapy cohorts, dose-optimization cohorts, a food-effect cohort, and a combination cohort evaluating DZR123 with enzalutamide in metastatic castration-resistant prostate cancer. The study also includes long-term follow-up to monitor survival and the occurrence of second primary malignancies, with assessments conducted approximately every 3 months for the first 3 years and every 6 months thereafter.

Phase 1: Dose Escalation (Monotherapy) The initial phase of the study consists of a dose-escalation period using a traditional 3+3 design. Adult patients with advanced, relapsed, or refractory solid tumors or lymphomas receive escalating doses of DZR123 as monotherapy. The primary objective of this phase is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of DZR123. Dose-escalation decisions are based on safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary antitumor activity data. Patients are not randomized during this phase.

Phase 2: Dose Expansion and Optimization Phase 2 further evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of DZR123 in disease-specific cohorts and explores dose optimization and combination therapy approaches.

Cohorts M1-M6: Disease-Specific Monotherapy Patients are enrolled into disease-specific cohorts defined by tumor type and/or molecular characteristics, including adenine-thymine-rich interactive domain-containing protein 1A (ARID1A) mutations, BRCA1-associated protein 1 (BAP1) loss, lymphoma subtypes, and metastatic castration-resistant prostate cancer (mCRPC).

Cohorts M1, M5, and M6 use a Simon's two-stage design in which 10 patients are enrolled in Stage 1; if at least 1 response is observed, up to 19 additional patients are enrolled in Stage 2. Cohorts M2 and M3 also begin with a Simon's two-stage design and subsequently transition into dose-optimization stages. Cohort M4 enrolls approximately 20 patients with lymphoma in a single stage without further expansion. Patients are not randomized except during dose-optimization stages in Cohorts M2 and M3.

Dose Optimization in Cohorts M2 and M3 For ovarian clear cell carcinoma (Cohort M2) and endometrial carcinoma (Cohort M3), dose optimization is conducted after initial cohort expansion. In Stage 2a, participants are randomized 1:1 to receive DZR123 200 mg or 300 mg once daily. Depending on predefined efficacy and safety criteria, Stage 2b may enroll additional participants in one or both dose groups to further evaluate the optimal dose for future clinical development.

Cohort M7: Food-Effect Evaluation Cohort M7 evaluates the effect of a high-fat, high-calorie meal on the pharmacokinetics of DZR123 in patients with ARID1A wild-type endometrial carcinoma. Approximately 20 participants receive a single dose of DZR123 with a standardized meal on Cycle 1 Day 1, followed by continued DZR123 administration. Results from this cohort may inform future administration instructions regarding food intake in subsequent DZR123 studies and cohorts.

Cohort M8: DZR123 in Combination With Enzalutamide Cohort M8 evaluates DZR123 in combination with enzalutamide in participants with metastatic castration-resistant prostate cancer and consists of two parts.

  • Part 1 (Dose Escalation): Participants receive escalating doses of DZR123 in combination with enzalutamide 160 mg once daily. Dose escalation is guided by a Bayesian logistic regression model (BLRM) using the Escalation With Overdose Control (EWOC) principle to determine the RP2D for the combination. Approximately 30 participants are enrolled. A 7-day enzalutamide run-in period may be used prior to combination treatment.
  • Part 2 (Dose Expansion): Following selection of the RP2D, approximately 40 additional participants receive DZR123 at the selected dose in combination with enzalutamide to further evaluate safety, tolerability, PK, PD, and antitumor activity. Amendment 15 increased the planned enrollment in Part 2 from approximately 15 to approximately 40 participants and revised the primary efficacy assessment to focus on prostate-specific antigen response.

The study includes safety monitoring throughout treatment and follow-up, including collection of adverse events, laboratory assessments, tumor evaluations, and dedicated surveillance for second primary malignancies associated with EZH1/2 inhibition.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France, 33000
        • Withdrawn
        • CHU Bordeaux Hopital Saint Andre
      • Bordeaux, France, 33000
        • Recruiting
        • CLCC Institut Bergonie
        • Principal Investigator:
          • Antoine Italiano
      • Lille, France, 59000
        • Recruiting
        • Centre Oscar Lambret
        • Principal Investigator:
          • Cyril Abdeddaim
      • Lyon, France, 69008
        • Recruiting
        • Centre Leon Berard
        • Principal Investigator:
          • Medhi Brahmi
      • Nantes, France, 44093 Cedex 1
        • Recruiting
        • CHU Nantes Hopital Hotel Dieu
        • Principal Investigator:
          • Caroline Viala
      • Saint-Herblain, France, 44800
        • Recruiting
        • CHU Nantes Hopital Nord Laennec
        • Principal Investigator:
          • Caroline Viala
      • Strasbourg, France, 67098
        • Recruiting
        • Hopital Hautepierre
        • Principal Investigator:
          • Lauriane EBERST
      • Villejuif, France, 94805 Cedex
        • Recruiting
        • Gustave Roussy
        • Principal Investigator:
          • Vincent Ribrag
  • Italy
      • Bologna, Italy, 40138
        • Completed
        • Irccs University Hospital of Bologna
      • Milan, Italy, 20141
        • Recruiting
        • European Institute of Oncology (IEO), IRCCS
        • Principal Investigator:
          • Franco Nole
      • Milan, Italy, 20133
        • Recruiting
        • National Cancer Institute, IRCCS
        • Principal Investigator:
          • Mara Mantiero
      • Milan, Italy, 20141
        • Completed
        • European Institute of Oncology (IEO), IRCCS
      • Milan, Italy, 20159
        • Recruiting
        • Humanitas San Pio X
        • Principal Investigator:
          • Domenica Lorusso
      • Milan, Italy, 20133
        • Withdrawn
        • National Cancer Institute, IRCCS
      • Roma, Italy, 00168
        • Recruiting
        • University Polyclinic Foundation "Agostino Gemelli" - IRCCS
        • Principal Investigator:
          • Vanda Salutari
      • Rozzano, Italy, 20089
        • Recruiting
        • Gruppo Humanitas - Humanitas Research Hospital - Cancer Center
        • Principal Investigator:
          • Carmelo Carlo-Stella
  • Poland
      • Gdansk, Poland, 80-214
        • Recruiting
        • University Teaching Centre, Early Clinical Trials Unit
        • Principal Investigator:
          • Rafal Dziadziuszko
      • Krakow, Poland, 30-510
        • Withdrawn
        • Pratia McM Krakow
      • Lodz, Poland, 93-338
        • Withdrawn
        • Polish Mother's Memorial Hospital-Research Institute
      • Poznan, Poland, 60-569
        • Recruiting
        • University Teaching Hospital in Poznan, Department of Gynecologic Oncology
        • Principal Investigator:
          • Radoslaw Madry
      • Poznan, Poland, 60-192
        • Completed
        • Pratia - Poznan
      • Warsaw, Poland, 02-781
        • Completed
        • Maria Sklodowska-Curie - National Research Institute of Oncology
  • South Korea
      • Daegu, South Korea, 42601
        • Withdrawn
        • Keimyung University - Dongsan Medical Center
      • Goyang-si, South Korea, 10408
        • Completed
        • National Cancer Center
      • Incheon, South Korea, 21565
        • Recruiting
        • Gachon University Gil Medical Center
        • Principal Investigator:
          • Kwang-Beom Lee
      • Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center
        • Principal Investigator:
          • Shin Wha Lee
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
        • Principal Investigator:
          • Jae Weon Kim
      • Seoul, South Korea, 03722
        • Recruiting
        • Severance Hospital, Yonsei University Health System
        • Principal Investigator:
          • Jung-Yun Lee
      • Seoul, South Korea, 06273
        • Recruiting
        • Gangnam Severance Hospital
        • Principal Investigator:
          • Jae-Hoon Kim
      • Seoul, South Korea, 06591
        • Withdrawn
        • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Spain
      • Barcelona, Spain, 08036
        • Recruiting
        • Hospital Clinic of Barcelona
        • Principal Investigator:
          • Begona Mellado Gonzalez
      • Barcelona, Spain, 08035
        • Recruiting
        • University Hospital Vall d'Hebron
        • Principal Investigator:
          • Ana Oaknin
      • Girona, Spain, 17007
        • Recruiting
        • University Hospital of Girona Dr. Josep Trueta
        • Principal Investigator:
          • Maria Pilar Barretina Ginesta
      • L'Hospitalet de Llobregat, Spain, 08908
        • Withdrawn
        • Catalan Institute of Oncology, Hospital Duran i Reynals
      • Madrid, Spain, 28040
        • Recruiting
        • University Hospital Foundation Jimenez Diaz
        • Principal Investigator:
          • Bernard Gaston Doger De Speville
      • Madrid, Spain, 28034
        • Recruiting
        • University Hospital Ramón y Cajal
        • Principal Investigator:
          • Teresa Alonso Gordoa
      • Madrid, Spain, 28041
        • Completed
        • University Hospital 12 de Octubre
      • Madrid, Spain, 28027
        • Recruiting
        • University Clinic of Navarra - Madrid
        • Principal Investigator:
          • Antonio Gonzalez Martin
      • Madrid, Spain, 28223
        • Recruiting
        • University Hospital Quiron Madrid
        • Principal Investigator:
          • Jesus Fuentes Antras
      • Madrid, Spain, 28040
        • Recruiting
        • University Hospital Clinical San Carlos, Department of Medical Oncology
        • Principal Investigator:
          • Jorge Bartolome Arcilla
      • Majadahonda, Spain, 28222
        • Recruiting
        • University Hospital Puerta de Hierro Majadahonda
        • Principal Investigator:
          • Aranzazu Gonzalez-Del-Alba
      • Palma, Spain, 07120
        • Recruiting
        • University Hospital Son Espases
        • Principal Investigator:
          • Marina Justo de la Pena
      • Pamplona, Spain, 31008
        • Recruiting
        • University Clinic of Navarra - Pamplona
        • Principal Investigator:
          • Antonio Gonzalez Martin
      • Sabadell, Spain, 08208
        • Recruiting
        • Parc Tauli Health Corporation
        • Principal Investigator:
          • Enrique Gallardo Diaz
      • Salamanca, Spain, 37007
        • Completed
        • University Clinical Hospital of Salamanca
      • Santiago de Compostela, Spain, 15706
        • Recruiting
        • University Hospital Complex of Santiago (CHUS)
        • Principal Investigator:
          • Maria Teresa Curiel Garcia
      • Seville, Spain, 41013
        • Recruiting
        • University Hospital Virgen del Rocio (HUVR)
        • Principal Investigator:
          • Alejandro Falcon Gonzalez
      • Valencia, Spain, 46026
        • Recruiting
        • University and Polytechnic Hospital La Fe
        • Principal Investigator:
          • Regina Girones Sarrio
      • Valencia, Spain, 46009
        • Recruiting
        • Valencia Oncology Institute (IVO)
        • Principal Investigator:
          • Ignacio Romero Noguera
  • United Kingdom
      • Bath, United Kingdom, BA1 3NG
        • Withdrawn
        • Royal United Hospital, Department of Oncology/Hematology
      • Leicester, United Kingdom, LE1 5WW
        • Recruiting
        • Leicester Royal Infirmary
        • Principal Investigator:
          • Harriet Walter
      • London, United Kingdom, SW3 6JJ
        • Withdrawn
        • Royal Marsden Hospital - London
      • London, United Kingdom, SW7 2AZ
        • Withdrawn
        • Imperial College Healthcare NHS Trust
      • Manchester, United Kingdom, M20 4BX
        • Completed
        • The Christie NHS Foundation Trust, Department of Medical Oncology
      • Oxford, United Kingdom, OX3 7LE
        • Withdrawn
        • Churchill Hospital
      • Southampton, United Kingdom, SO16 6YD
        • Withdrawn
        • University Hospital Southampton NHS foundation Trust
      • Sutton, United Kingdom, SM2 5PT
        • Completed
        • Royal Marsden Hospital - Sutton
      • Taunton, United Kingdom, TA1 5DA
        • Completed
        • Musgrove Park Hospital
  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Withdrawn
        • H. Lee Moffitt Cancer Center & Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322-1013
        • Recruiting
        • Winship Cancer Institute of Emory University
        • Principal Investigator:
          • Beryl Manning-Geist, MD
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medical Center
        • Principal Investigator:
          • Hedy Lee Kindler, MD
      • Maywood, Illinois, United States, 60153
        • Withdrawn
        • Loyola University Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Withdrawn
        • University of Maryland Greenebaum Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Ryan Sullivan, MD
      • Boston, Massachusetts, United States, 02215-5450
        • Completed
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Withdrawn
        • University of Michigan Hospitals
      • Grand Rapids, Michigan, United States, 49546
        • Active, not recruiting
        • South Texas Accelerated Research Therapeutics (START) - Midwest Location
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Completed
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Withdrawn
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10065
        • Withdrawn
        • Weill Medical College of Cornell University
      • New York, New York, United States, 10016
        • Completed
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • New York, New York, United States, 10065
        • Withdrawn
        • Memorial Sloan Kettering Cancer Center - NYC
      • Rochester, New York, United States, 14642
        • Withdrawn
        • University of Rochester Medical Center, James P. Wilmot Cancer Center
      • The Bronx, New York, United States, 10467-2490
        • Withdrawn
        • Montefiore Medical Center, Montefiore Medical Center Laboratories
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Withdrawn
        • University of Cincinnati Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Abramson Cancer Center of the University of Pennsylvania
        • Principal Investigator:
          • Lainie Martin, MD
    • Texas
      • San Antonio, Texas, United States, 78229
        • Completed
        • South Texas Accelerated Research Therapeutics
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia Health System
        • Principal Investigator:
          • Linda Duska, MD
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Swedish Cancer Institute
        • Principal Investigator:
          • Charles Drescher, MD
      • Seattle, Washington, United States, 98109-1023
        • Recruiting
        • Fred Hutchinson Cancer Center
        • Principal Investigator:
          • Kalyan Banda, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1
Eligible participants with advanced tumors will receive escalating doses of Tulmimetostat once per day orally.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
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.
Drug: Tulmimetostat
Tulmimetostat dosed once per day orally in 28 day cycles
Other Names:
  • DZR123
Drug: Enzalutamide
Enzalutamide dosed once per day orally in 28 day cycles

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tulmimetostat Monotherapy Phase 2: Time-to-progression (TTP)
Time Frame: Up to 30 months
TTP defined as duration from the start of treatment until the disease progression
Up to 30 months
Cohort M8 Part 1: Prostate-Specific Antigen 50 (PSA50) Response
Time Frame: Up to 18 months
PSA50 response defined as PSA decline by >=50% from baseline
Up to 18 months
Cohort M8 Part 1: Number of participants experiencing Dose-limiting toxicities (DLTs)
Time Frame: DLTs assessed during Cycle 1 (cycle = 28 days)
To establish dose-toxicity relationship between Tulmimetostat and enzalutamide combination
DLTs assessed during Cycle 1 (cycle = 28 days)
Cohort M8 Part 2: Time to Prostate-Specific Antigen (PSA) Progression
Time Frame: Up to 18 months
Time to PSA progression defined as the time from first dose to PSA progression
Up to 18 months
Tulmimetostat Monotherapy (Phase 1 & 2) and Cohort M8 (Parts 1 & 2): Incidence Rate of Adverse Events (AEs)
Time Frame: Up to 18 months
Number of Participants With 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)
Time Frame: Up to 18 months
Venous whole blood samples will be collected for pharmacokinetics characterization. Cmax of Tulmimetostat will be listed and summarized using descriptive statistics.
Up to 18 months
Tulmimetostat Monotherapy (Phase 1 & 2), Cohort M7 and Cohort M8 (Parts 1 & 2): Time of maximum observed plasma concentration (Tmax)
Time Frame: Up to 18 months
Venous whole blood samples will be collected for pharmacokinetics characterization. Tmax of Tulmimetostat will be listed and summarized using descriptive statistics.
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)
Time Frame: Up to 18 months
Venous whole blood samples will be collected for pharmacokinetics characterization. AUC0-last of Tulmimetostat will be listed and summarized using descriptive statistics.
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)
Time Frame: Up to 18 months
Venous whole blood samples will be collected for pharmacokinetics characterization. AUC0-Inf of Tulmimetostat will be listed and summarized using descriptive statistics.
Up to 18 months
Tulmimetostat Monotherapy (Phase 1 & 2) and Cohort M7: Terminal elimination half-life (T1/2)
Time Frame: Up to 18 months
Venous whole blood samples will be collected for pharmacokinetics characterization. T 1/2 of Tulmimetostat will be listed and summarized using descriptive statistics.
Up to 18 months
Tulmimetostat Monotherapy (Phase 1 & 2), Cohort M7 and Cohort M8 (Parts 1 & 2): Plasma concentrations prior to the next dose-trough (Cmin)
Time Frame: Up to 18 months
Venous whole blood samples will be collected for pharmacokinetics characterization. Cmin of Tulmimetostat will be listed and summarized using descriptive statistics.
Up to 18 months
Tulmimetostat Monotherapy (Phase 1) and Cohort M8 (Part 1): Objective Response Rate (ORR)
Time Frame: Up to 30 months
ORR defined as proportion of patients with a best overall response of complete response (CR) or partial response (PR), per Investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1 or applicable response criteria)
Up to 30 months
Tulmimetostat Monotherapy (Phase 1 & 2): ORR per Gynecologic Cancer Intergroup (GCIG)
Time Frame: Up to 30 months
ORR per Gynecologic Cancer Intergroup (GCIG)-defined CA-125 response criteria (ovarian cancer patients)
Up to 30 months
Tulmimetostat Monotherapy (Phase 1): ORR per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
Time Frame: Up to 30 months
ORR per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) (in Phase 1 prostate cancer patients only)
Up to 30 months
Tulmimetostat Monotherapy (Phase 1 & 2) and Cohort M8 (Part 2): Progression-free survival (PFS)
Time Frame: Up to 30 months
PFS defined as the time from first dose to confirmed disease progression or death
Up to 30 months
Tulmimetostat Monotherapy (Phase 1 & 2) and Cohort M8 (Parts 1 & 2): Duration of response (DOR)
Time Frame: Up to 30 months
DOR defined as the time from the date of first response to the date of confirmed disease progression
Up to 30 months
Tulmimetostat Monotherapy (Phase 1 & 2): Time to response (TTR)
Time Frame: Up to 30 months
TTR defined as the time from first dose to date of first response
Up to 30 months
Tulmimetostat Monotherapy (Phase 1 & 2) and Cohort M8 (Part 1): Disease Control Rate (DCR)
Time Frame: Up to 30 months
DCR defined as the proportion of patients with a best overall response of CR, PR, or stable disease (SD)
Up to 30 months
Tulmimetostat Monotherapy (Phase 2) and Cohort M8 (Part 2): Overall survival (OS)
Time Frame: Up to 30 months
OS defined as the time from first dose to death
Up to 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 18, 2019

Primary Completion (Estimated)

February 27, 2030

Study Completion (Estimated)

February 27, 2030

Study Registration Dates

First Submitted

September 23, 2019

First Submitted That Met QC Criteria

September 24, 2019

First Posted (Actual)

September 26, 2019

Study Record Updates

Last Update Posted (Actual)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 18, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDZR123A02101
  • CPI-0209-01 (Other Identifier: Constellation Pharmaceuticals)
  • 2023-508002-20-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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