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Recruiting Phase 1/2

TulmiSTAR-02: A Phase I/II Open-label Study of Tulmimetostat in Combination With Darolutamide vs. Darolutamide, and Tulmimetostat With Abiraterone in Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

NCT07190300 · tracked via the Priya Life Science Italy tracker
Phase
Phase 1/2
Started
2026-01-13
Last updated
2026-09-29

Condition(s) studied

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Investigational drug(s) / intervention(s)

Tulmimetostat →Darolutamide →Abiraterone →Prednisone/Prednisolone →Androgen Deprivation Therapy (ADT)

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.

Study 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.

Eligibility

Sex
MALE
Min age
18 Years
Max age
—
Healthy volunteers
No
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

Primary outcome measure(s)

  • Phase I (Group A and Group B): Dose-limiting toxicities (DLTs) — From the first dose of study treatment through the end of Cycle 1, up to 28 days
    A dose-limiting toxicity was defined as an adverse event or abnormal laboratory value that was not clearly attributable to the underlying disease or an extraneous cause, occurred during the first 28 days of treatment with tulmimetostat, and met the protocol-defined dose-limiting toxicity criteria. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dose-limiting toxicities were included in the Bayesian Logistic Regression Model used to support dose-escalation decisions.
  • Phase I (Group A and Group B): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) — From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months
    The incidence, type, frequency, seriousness, and severity of adverse events and serious adverse events will be summarized. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
  • Phase I (Group A and Group B): Number of Participants with dose adjustments — From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months
    The number of participants with dose reductions, dose interruptions, or permanent discontinuations, including the reasons for the dose adjustments, will be summarized by treatment group and dose cohort.
  • Phase I (Group A and Group B): Dose Intensity — From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months
    Dose intensity, calculated as the actual cumulative dose received divided by the actual duration of exposure, and relative dose intensity, calculated as the dose intensity divided by the planned dose intensity, will be summarized using descriptive statistics for each study drug.
  • Phase I (Group A and Group B): Duration of exposure to each study drug — From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months
    The duration of exposure, in months, to each study drug will be summarized using descriptive statistics by treatment group and dose cohort.
  • Phase II (Group A): Prostate-Specific Antigen (PSA) response rate of < 0.2 ng/mL at Month 6 — At Month 6, with confirmation by a second prostate-specific antigen assessment performed at least 3 weeks later
    Prostate-Specific Antigen (PSA) response rate is defined as the proportion of participants who achieved a prostate-specific antigen level below 0.2 ng/mL at Month 6, confirmed by a second prostate-specific antigen assessment performed at least 3 weeks later.

Trial sites (31)

FacilityCityRegionStatus
Univ of Alabama at Birmingham Birmingham Alabama Recruiting
Uni Of Iowa Hospitals And Clinics Iowa City Iowa Recruiting
University of Kansas Cancer Center Westwood Kansas Recruiting
Wichita Urology Group PA Wichita Kansas Recruiting
Duke University Medical Center Durham North Carolina Recruiting
Medical University of South Carolina MUSC Charleston South Carolina Recruiting
Carolina Urologic Research Center Myrtle Beach South Carolina Recruiting
Huntsman Cancer Institute Salt Lake City Utah Recruiting
Novartis Investigative Site Camperdown New South Wales Withdrawn
Novartis Investigative Site Wollongong New South Wales Recruiting
Novartis Investigative Site Porto Alegre Rio Grande do Sul Recruiting
Novartis Investigative Site Montreal Quebec Recruiting
Novartis Investigative Site Guangzhou China Recruiting
Novartis Investigative Site Créteil France Recruiting
Novartis Investigative Site Lille France Recruiting
Novartis Investigative Site Nantes France Recruiting
Novartis Investigative Site Jena Thuringia Recruiting
Novartis Investigative Site Essen Germany Recruiting
Novartis Investigative Site Hong Kong Hong Kong Recruiting
Novartis Investigative Site Budapest Hungary Recruiting
Novartis Investigative Site Budapest Hungary Recruiting
Novartis Investigative Site Szeged Hungary Recruiting
Novartis Investigative Site Rozzano MI Recruiting
Novartis Investigative Site Verona VR Recruiting
Novartis Investigative Site Seoul South Korea Recruiting
Novartis Investigative Site Seoul South Korea Recruiting
Novartis Investigative Site Madrid Spain Recruiting
Novartis Investigative Site Madrid Spain Recruiting
Novartis Investigative Site Madrid Spain Recruiting
Novartis Investigative Site Ankara Sihhiye Altindag Recruiting
Novartis Investigative Site London United Kingdom Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07190300 on ClinicalTrials.gov ↗ ← All trials in Italy