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)
Condition(s) studied
Investigational drug(s) / intervention(s)
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
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)
| Facility | City | Region | Status |
|---|---|---|---|
| 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 |
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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.
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