Last Update: Jun 23, 2026 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 ClinicalTrials.gov Identifier: [NCT07190300](https://clinicaltrials.gov/ct2/show/NCT07190300) Novartis Reference Number:CDZR123C12101 [See if you Pre-qualify](#trial-eligibility "See if you Pre-qualify") All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. ## Study Description The purpose of the study is to evaluate the safety, tolerability, and efficacy of the two different treatment combinations of tulmimetostat in participants with de novo or recurrent Metastatic Hormone-Sensitive Prostate Cancer (mHSPC). The study consists of two phases: 1\. Phase I: The Phase I part includes two groups: Part 1 will assess the combination of tulmimetostat with darolutamide (Group A), and Part 2 will assess tulmimetostat with abiraterone (Group B). The primary objective of Phase I is to determine the recommended dose escalations (RDEs) for each combination, with enrollment using a staggered approach between groups. Participants in both groups will continue androgen deprivation therapy (ADT) to maintain castrate testosterone levels (\\<50 ng/dL or \\<1.7 nmol/L), as determined by the investigator based on local guidelines. In Group B, abiraterone will be administered with an oral corticosteroid (prednisone or prednisolone) per local prescribing information. 2\. Phase II: Phase II is a randomized, open-label, multicenter dose-expansion study to further evaluate the recommended dose(s) of tulmimetostat in combination with darolutamide and provide proof-of-concept for efficacy and safety. Participants will be randomized to receive tulmimetostat plus darolutamide or darolutamide alone. Eligible participants include those with metastatic hormone-sensitive prostate cancer (mHSPC) who are either de novo or recurrent, without prior radioligand therapy, but who may have received prior taxane-based chemotherapy and/or androgen receptor pathway inhibitors (ARPIs), excluding darolutamide. The study evaluates tulmimetostat-based combinations as potential treatment options for men with mHSPC. The study for each participant consists of a screening period, a study treatment period followed by a post treatment long-term follow-up. Condition Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Phase Phase1, Phase2 Overall Status Recruiting Number of Participants181 Start Date Jan 13, 2026 Completion Date Aug 02, 2032 Gender Male Age(s) 18 Years - (Adult, Older Adult) ## Interventions Drug ### Abiraterone 1000 mg is administered orally QD Drug ### Darolutamide 600 mg is administered orally BID Drug ### Tulmimetostat Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s)) ## Eligibility 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 Australia #### Novartis Investigative Site Recruiting Wollongong,New South Wales,2500,Australia Brazil #### Novartis Investigative Site Recruiting Porto Alegre,Rio Grande do Sul,90610-001,Brazil Canada #### Novartis Investigative Site Recruiting Montreal,Quebec,H2x 1r9,Canada China #### Novartis Investigative Site Recruiting Guangzhou,510060,China France #### Novartis Investigative Site Recruiting Lille,59020,France #### Novartis Investigative Site Recruiting Nantes,44093,France #### Novartis Investigative Site Recruiting Créteil,94010,France Germany #### Novartis Investigative Site Recruiting Jena,Thuringia,07740,Germany #### Novartis Investigative Site Recruiting Essen,45147,Germany Hong Kong #### Novartis Investigative Site Recruiting Hong Kong,999077,Hong Kong Hungary #### Novartis Investigative Site Recruiting Budapest,H-1083,Hungary #### Novartis Investigative Site Recruiting Szeged,6725,Hungary #### Novartis Investigative Site Recruiting Budapest,H 1122,Hungary Italy #### Novartis Investigative Site Recruiting Rozzano,MI,20089,Italy #### Novartis Investigative Site Recruiting Verona,VR,37134,Italy South Korea #### Novartis Investigative Site Recruiting Seoul,05505,South Korea #### Novartis Investigative Site Recruiting Seoul,06591,South Korea Spain #### Novartis Investigative Site Recruiting Madrid,28222,Spain #### Novartis Investigative Site Recruiting Madrid,28040,Spain #### Novartis Investigative Site Recruiting Madrid,28034,Spain Turkey (Türkiye) #### Novartis Investigative Site Recruiting Ankara,Sihhiye-Altindag,06230,Turkey (Türkiye) United Kingdom #### Novartis Investigative Site Recruiting London,W1g 6ad,United Kingdom United States #### University of Kansas Cancer Center Recruiting Westwood,Kansas,66205,United States ###### Haoran Li ###### Katie Looney Email: #### Wichita Urology Group PA Recruiting Wichita,Kansas,67226,United States ###### Timothy Richardson ###### Tyler Gentry Email: #### Univ of Alabama at Birmingham Recruiting Birmingham,Alabama,35294-3300,United States ###### Luke Hanna Email: ###### Joelle Hamilton #### Carolina Urologic Research Center Recruiting Myrtle Beach,South Carolina,29572,United States ###### Lindsey Rabon Phone: [843-839-1679](tel:843-839-1679) Email: ###### Neal Shore #### Medical University of South Carolina MUSC Recruiting Charleston,South Carolina,29425,United States ###### Renee Tucker Phone: [843-792-7560](tel:843-792-7560) Email: ###### Kevin Becker #### Huntsman Cancer Institute Recruiting Salt Lake City,Utah,84112,United States ###### Neeraj Agarwal ###### Alena Turner Email: #### Uni Of Iowa Hospitals And Clinics Recruiting Iowa City,Iowa,52242,United States ###### Kerri Fitch Email: ###### Fernando Maciel Barbosa #### Duke University Medical Center Recruiting Durham,North Carolina,27710,United States ###### Tykeytra Dale Email: ###### Jeffrey Shevach ## Worldwide Contacts If the location of your choosing does not feature any contact detail, please reach out using the information below. #### Novartis Pharmaceuticals Phone: [ +41613241111](tel:+41613241111) Email: #### Novartis Pharmaceuticals Phone: [ 1-888-669-6682](tel:1-888-669-6682) Email: