Home › Trials › NCT07190300

Tulmimetostat with darolutamide or abiraterone for metastatic hormone-sensitive prostate cancer

TulmiSTAR-02: A Two-part Phase I Dose Escalation Study of Tulmimetostat (DZR123) in Combination With Darolutamide or Abiraterone Followed by Open-label, Randomized, Phase II Dose Expansion Study to Assess the Safety and Efficacy of Tulmimetostat in Combination With Darolutamide Versus Darolutamide Alone in Patients With Metastatic Hormone-sensitive Prostate Cancer

Phase1; Phase2 Interventional Novartis · NCT07190300

This trial will test whether adding tulmimetostat to darolutamide or abiraterone helps men with metastatic hormone-sensitive prostate cancer control their cancer better.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment181 (estimated)
Ages18 Years and up
SexMale
SponsorNovartis Industry-sponsored
Drugs / interventionsradiation, chemotherapy, prednisone
Locations25 sites (Iowa City, Iowa and 24 other locations)
Trial IDNCT07190300 on ClinicalTrials.gov

What this trial studies

The trial has a Phase I dose-finding portion with two parallel groups testing tulmimetostat combined with darolutamide (Group A) or with abiraterone plus corticosteroid (Group B) to determine recommended dose escalations while patients remain on androgen deprivation therapy. Phase II is an open-label, randomized dose-expansion comparing tulmimetostat plus darolutamide versus darolutamide alone to provide proof-of-concept for safety and antitumor activity. Eligible participants are men with de novo or recurrent mHSPC who maintain castrate testosterone and meet performance and organ function criteria, with limited prior taxane or ARPI exposure allowed under protocol rules. Key outcomes include safety, tolerability, recommended doses, and early signals of efficacy such as PSA and radiographic responses.

Who should consider this trial

Good fit: Adult men with de novo or recurrent metastatic hormone-sensitive prostate cancer who are castrate on ADT, have ECOG 0–2, adequate organ function, and meet the protocol timing limits for prior therapies are the intended candidates.

Not a fit: Patients with neuroendocrine or small cell features, prior exposure to darolutamide, prior radioligand therapy, or who do not meet ADT/timing or organ function requirements are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve tumor control or delay progression compared with standard ARPI therapy alone.

How similar studies have performed: Combining an EZH2 inhibitor with androgen receptor pathway inhibitors is a novel approach in prostate cancer with supportive preclinical data but limited clinical proof-of-concept to date.

Eligibility criteria

Show full inclusion / exclusion criteria 
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:

  1. 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
  2. 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.
     * Phase II: 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.
* 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.

Other inclusion/exclusion criteria may apply

Where this trial is running

Iowa City, Iowa and 24 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Hormone-Sensitive Prostate CancerEnhancer of Zeste Homolog 2Androgen ReceptorAndrogen Receptor Pathway InhibitorsProstate-Specific AntigenBiochemical Response RateTulmiSTAR-02
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.