Recruiting
Phase 1
Phase 2

Tulmimetostat

Sponsor:

Novartis Pharmaceuticals

Code:

NCT07190300

Conditions

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Tulmimetostat

Darolutamide

Abiraterone

Prednisone/Prednisolone

Androgen Deprivation Therapy (ADT)

Study Details

Brief summary:

The purpose of this study is to evaluate the safety, tolerability, and efficacy of two different treatment combinations of tulmimetostat in participants with de novo or recurrent metastatic hormone-sensitive prostate cancer (mHSPC). Phase I aims to determine the recommended dose(s) for expansion (RDE) of tulmimetostat in combination with darolutamide or abiraterone. Phase II is designed to further evaluate the efficacy and safety of tulmimetostat in combination with darolutamide compared with darolutamide alone in participants with mHSPC.

Conditions

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Study ID

NCT07190300

Start date

Jan 13, 2026

Status verified date

Sep, 2026

Completion date

Aug 2, 2032

Anticipated

Primary completion date

Aug 2, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

  • Adult men ≥ 18 years old with de novo or recurrent mHSPC (without neuroendocrine or small cell features). The tumor lesion(s) may be located in the bone, soft tissue/visceral region, or both.
  • Participants must have castrate levels of testosterone, i.e., ≤ 50 ng/dL (≤ 1.7 nM).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Adequate bone marrow and organ function
  • Prior ADT: Participants must have started ADT at least 1 month (at least 28 days) but no more than 12 months before study entry and be willing to continue ADT during treatment
  • Prior taxane use for mHSPC is permitted:

  • Phase I and II: Participants may have received, but not progressed on, one prior taxane-based therapy.
  • Phase II: Limited to 25% participants with prior taxane use.
  • Prior ARPI is allowed in both Phase I and Phase II:

  • Prior ARPI use in biochemical recurrence (BCR) or curative treatment is allowed for any duration, provided therapy was discontinued and participant had no evidence of conventional imaging positive metastatic disease at that time
  • Prior ARPI use in mHSPC is permitted but not mandated. If participants meet all study eligibility criteria, they are required to stop their prior ARPI after providing informed consent and remain off ARPI until Cycle 1 Day 1, when study treatment is initiated.

  • Phase I: Allowed for any duration.
  • Phase II: Allowed prior exposure to ARPI is ≤4 months. Participants with ongoing use of darolutamide are not eligible.

Participants with ongoing ARPI are eligible for a switch from their ongoing ARPI therapy if they have not progressed to CRPC disease, and meet any of the criteria, indicative of suboptimal biochemical response, or intolerability, as assessed by the Investigator:

  • Evidence of insufficient PSA control or suboptimal PSA response, defined as PSA ≥ 0.2 ng/mL after 6-12 months ADT and no more than 4 months of current ARPI therapy in mHSPC with declining or stable PSA trend. Eligibility based on biochemical progression should be supported by objective evidence (e.g. PSA results).
  • Intolerance and non-compliance: Participant's inability to tolerate or comply with the prescribed ARPI. The site should maintain documentation to support the appropriateness of therapy changes resulting from intolerance or non-compliance.

• Other permitted prior local therapy for mHSPC:
  • Phase I and II: Prior prostate-directed radiation or surgical intervention. Radiation must be completed before study entry; surgery at least 2 weeks prior.

Key Exclusion Criteria:

  • Participants with evidence of mCRPC or biochemical recurrence / PSA only disease or asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy and with normal PSA for ≥ 1 year prior to the start of study treatment.
  • Participants who have not received ARPI treatment for mHSPC and present with PSA levels of ≤0.5 ng/mL or those with prior/ongoing ARPI treatment presenting with PSA levels of ≤ 0.2 ng/mL prior to treatment assignment/randomization.
  • Participants with CNS metastases are excluded unless:

  • they have received prior therapy (e.g. surgery, radiotherapy, gamma knife), are neurologically stable and asymptomatic.
  • they are not receiving corticosteroid for the purpose of maintaining neurologic integrity and have baseline and subsequent radiological imaging of the brain.
  • Concurrent use of first-generation anti-androgens (like bicalutamide). Prior use of a first-generation anti-androgen drug in the context of ADT initiation with a GNRH analog is allowed, provided it was administered for ≤14 days and the last dose was administered ≥7 days from the study entry.
  • Systemic ketoconazole is used as antineoplastic treatment for prostate cancer.
  • Previous exposure to radioligand therapy.
  • Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.
  • Previous treatment with any Polycomb Repressive Complex 2 (PRC2) inhibitor, including but not limited to Enhancer of Zeste Homolog 2 (EZH2) inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors.
  • Herbal products that may decrease PSA levels within 4 weeks prior to the start of study drug treatment and while on study.
  • Participants taking prohibited medication(s) (e.g., strong CYP3A4 inducers or strong or moderate CYP3A4 inhibitors that cannot be stopped within 7 days or 5 half-lives (whichever is longer) prior to study treatment and for the duration of the study treatment or prohibited herbal product(s) that cannot be stopped 7 days prior to study treatment.
  • Have a history of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years. Participants with a history of leukemia/lymphoma and/or MDS are not eligible.

Other inclusion/exclusion criteria may apply

Study Design

Enrollment

181 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase I: Group A (part 1)

Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT) throughout the study.

experimental: Phase I: Group B (part 2)

Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with abiraterone 1000 mg orally once daily (QD). Participants will continue androgen deprivation therapy (ADT). Abiraterone will be administered with prednisone/prednisolone according to local prescribing information.

experimental: Phase II: Arm 1

Tulmimetostat Dose 1 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT).

experimental: Phase II: Arm 2 (Optional)

Tulmimetostat Dose 2 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT). This arm will be included if two recommended dose(s) for expansion are selected from Phase I.

active comparator: Phase II: Arm 3 (Control)

Darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT).

Interventions

Tulmimetostat

Tulmimetostat is an oral dual EZH1/EZH2 inhibitor administered once daily. In Phase I, escalating dose levels will be evaluated in combination with darolutamide or abiraterone. In Phase II, one or two dose levels selected from Phase I will be evaluated in combination with darolutamide.

Darolutamide

Darolutamide 600 mg administered orally twice daily (BID).

Abiraterone

Abiraterone 1000 mg administered orally once daily (QD) in combination with prednisone/prednisolone according to local prescribing information.

Prednisone/Prednisolone

Oral corticosteroid administered with abiraterone in Phase I Group B according to local prescribing information.

Androgen Deprivation Therapy (ADT)

Background therapy consisting of a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior orchiectomy to maintain castrate testosterone levels (<50 ng/dL \[<1.7 nmol/L\]). All participants will continue ADT throughout study participation.

Primary outcome measure

  • Phase I (Group A and Group B): Dose-limiting toxicities (DLTs) [ Time Frame: From the first dose of study treatment through the end of Cycle 1, up to 28 days ]
  • Phase I (Group A and Group B): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months ]
  • Phase I (Group A and Group B): Number of Participants with dose adjustments [ Time Frame: From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months ]
  • Phase I (Group A and Group B): Dose Intensity [ Time Frame: From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months ]
  • Phase I (Group A and Group B): Duration of exposure to each study drug [ Time Frame: From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months ]
  • Phase II (Group A): Prostate-Specific Antigen (PSA) response rate of < 0.2 ng/mL at Month 6 [ Time Frame: At Month 6, with confirmation by a second prostate-specific antigen assessment performed at least 3 weeks later ]

Central Contacts and Locations

Central contacts

Novartis Pharmaceuticals

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

Novartis Pharmaceuticals

+41613241111novartis.email@novartis.com

Locations

Univ of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294-3300

Contacts

Luke Hanna

lukehanna@uabmc.edu

Principal Investigator:

Joelle Hamilton

Uni Of Iowa Hospitals And Clinics

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Kerri Fitch

kerri-fitch@uiowa.edu

Principal Investigator:

Fernando Maciel Barbosa

University of Kansas Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Katie Looney

klooney2@kumc.edu

Principal Investigator:

Haoran Li

Wichita Urology Group PA

Recruiting

Wichita, Kansas, United States, 67226

Contacts

Tyler Gentry

tgentry@wichitaurology.com

Principal Investigator:

Timothy Richardson

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Tykeytra Dale

tykeytra.dale@duke.edu

Principal Investigator:

Jeffrey Shevach

Medical University of South Carolina MUSC

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Renee Tucker

843-792-7560tuckerr@musc.edu

Principal Investigator:

Kevin Becker

Carolina Urologic Research Center

Recruiting

Myrtle Beach, South Carolina, United States, 29572

Contacts

Lindsey Rabon

843-839-1679lindsey.rabon@startresearch.com

Principal Investigator:

Neal Shore

Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Alena Turner

alena.turner@hci.utah.edu

Principal Investigator:

Neeraj Agarwal

Novartis Investigative Site

Recruiting

Montreal, Quebec, Canada, H2X 1R9

More Information

Sponsor

Novartis Pharmaceuticals

Last update posted

Sep 29, 2026

Last verified

Sep, 2026

Keywords

  • Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
  • Enhancer of Zeste Homolog 2 (EZH2)
  • Androgen Receptor (AR)
  • Androgen Receptor Pathway Inhibitors (ARPIs)
  • Prostate-Specific Antigen (PSA)
  • PSA Response Rate
  • TulmiSTAR-02
  • Tulmimetostat (DZR123)
  • Darolutamide
  • Abiraterone

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Novartis Pharmaceuticals on 2026-09-29. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.