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NCT07190300PHASE1, PHASE2Recruiting

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)

Novartis Pharmaceuticals

Start Date

1/13/2026

Completion Date

8/2/2032

Summary

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).

Detailed Description

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Tulmimetostat

DRUG

Darolutamide

DRUG

Abiraterone

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Conditions

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Locations

Univ of Alabama at Birmingham

Birmingham, Alabama 35294-3300

United States

Uni Of Iowa Hospitals And Clinics

Iowa City, Iowa 52242

United States

University of Kansas Cancer Center

Westwood, Kansas 66205

United States

Wichita Urology Group PA

Wichita, Kansas 67226

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Medical University of South Carolina MUSC

Charleston, South Carolina 29425

United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina 29572

United States

Huntsman Cancer Institute

Salt Lake City, Utah 84112

United States

Novartis Investigative Site

Camperdown, New South Wales 2050

Australia

Novartis Investigative Site

Wollongong, New South Wales 2500

Australia

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul 90610-001

Brazil

Novartis Investigative Site

Montreal, Quebec H2X 1R9

Canada

Novartis Investigative Site

Guangzhou, 510060

China

Novartis Investigative Site

Créteil, 94010

France

Novartis Investigative Site

Lille, 59020

France

Novartis Investigative Site

Nantes, 44093

France

Novartis Investigative Site

Jena, Thuringia 07740

Germany

Novartis Investigative Site

Essen, 45147

Germany

Novartis Investigative Site

Hong Kong, 999077

Hong Kong

Novartis Investigative Site

Budapest, H 1122

Hungary

Novartis Investigative Site

Budapest, H-1083

Hungary

Novartis Investigative Site

Szeged, 6725

Hungary

Novartis Investigative Site

Rozzano, MI 20089

Italy

Novartis Investigative Site

Verona, VR 37134

Italy

Novartis Investigative Site

Seoul, 05505

South Korea

Novartis Investigative Site

Seoul, 06591

South Korea

Novartis Investigative Site

Madrid, 28034

Spain

Novartis Investigative Site

Madrid, 28040

Spain

Novartis Investigative Site

Madrid, 28222

Spain

Novartis Investigative Site

Ankara, Sihhiye-Altindag 06230

Turkey (Türkiye)

Novartis Investigative Site

London, W1G 6AD

United Kingdom