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 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CDZR123C121012025-521873-15-00
• Study Type: interventional
• Target: 155
• Locations: 11 countries
• Sites: 22

Brief 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).

Conditions

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Keywords

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC); Enhancer of Zeste Homolog 2 (EZH2); Androgen Receptor (AR); Androgen Receptor Pathway Inhibitors (ARPIs); Prostate-Specific Antigen (PSA); Biochemical Response Rate (BCR); TulmiSTAR-02

Outcome Measures

Primary Outcomes (6)

• Phase I (Group A and Group B): Dose-limiting toxicities (DLTs)

  A dose-limiting toxicity is defined as an adverse event or abnormal laboratory value, not clearly due to underlying disease or extraneous causes, that occurs within the first 28 days of treatment with tulmimetostat and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading. For the purpose of dose-escalation decisions, DLTs will be considered and included in the Bayesian Logistic Regression Model (BLRM).

  Up to 28 days

• Phase I (Group A and Group B): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.

  From date of randomization till 30 days safety fup, assessed up to approximately 79 months

• Phase I (Group A and Group B): Number of Participants with dose adjustments

  The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.

  From date of randomization till 30 days safety fup, assessed up to approximately 79 months

• Phase I (Group A and Group B): Dose Intensity

  Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity) will be summarized by means of descriptive statistics

  From date of randomization till 30 days safety fup, assessed up to approximately 79 months

• Phase I (Group A and Group B): Duration of exposure to each study drug

  Duration of exposure (in months) to each study drug will be summarized by means of descriptive statistics

  From date of randomization till 30 days safety fup, assessed up to approximately 79 months

• Phase II (Group A): Biochemical Response Rate (BCR)

  Biochemical Response Rate (BCR) is defined as prostate-specific antigen (PSA) decline to \< 0.2 ng/mL at 6 months, confirmed by a second PSA measurement ≥ 3 weeks later.

  From date of randomization till 30 days safety fup, assessed up to approximately 79 months

Secondary Outcomes (25)

• Phase I (Group A): Plasma concentrations of Tulmimetostat and Darolutamide

  Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.

• Phase I (Group A): AUC of Tulmimetostat and Darolutamide

  Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.

• Phase I (Group A): Cmax of Tulmimetostat and Darolutamide

  Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.

• Phase I (Group B): Plasma concentrations of Tulmimetostat and Abiraterone

  Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Day 2 (0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.

• Phase I (Group B): AUC of Tulmimetostat and Abiraterone

  Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Day 2 (0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.

Study Arms (5)

Phase I: Group A (part 1)

EXPERIMENTAL

Tulmimetostat oral (PO) once a day (QD) escalating doses + Darolutamide 600 mg twice a day (BID)

Drug: Tulmimetostat; Drug: Darolutamide

Phase I: Group B (part 2)

EXPERIMENTAL

Tulmimetostat PO QD escalating doses + Abiraterone 1000 mg PO QD

Drug: Tulmimetostat; Drug: Abiraterone

Phase II: Arm 1

EXPERIMENTAL

Tulmimetostat dose 1 PO + Darolutamide 600 mg PO BID

Drug: Tulmimetostat; Drug: Darolutamide

Phase II: Arm 2

EXPERIMENTAL

Tulmimetostat dose 2 PO + Darolutamide 600 mg PO BID

Drug: Tulmimetostat; Drug: Darolutamide

Phase II: Arm 3

ACTIVE COMPARATOR

Darolutamide 600 mg PO BID

Drug: Darolutamide

Interventions

Tulmimetostat DRUG

Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s))

Also known as: DZR123

Phase I: Group A (part 1); Phase I: Group B (part 2); Phase II: Arm 1; Phase II: Arm 2

Darolutamide DRUG

600 mg is administered orally BID

Phase I: Group A (part 1); Phase II: Arm 1; Phase II: Arm 2; Phase II: Arm 3

Abiraterone DRUG

abiraterone 1000 mg is administered orally QD

Phase I: Group B (part 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 but no more than 24 months before study entry and be willing to continue ADT during treatment
• Prior taxane use for mHSPC:
• \~ 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 (abiraterone, enzalutamide, darolutamide, or apalutamide) 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
• Phase I: Allowed for any duration.
• Phase II: Allowed prior exposure to ARPI is ≤6 months. Participants with ongoing use of darolutamide are not eligible.
• Note: Participants are required to stop their prior ARPI after providing their consent to join this study. 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.

You may not qualify if:

• 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 with PSA levels of ≤ 0.2 ng/mL at the start of study treatment.
• 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.
• Participants with epidural disease, canal disease, or prior spinal cord involvement are excluded unless these areas have been treated, are stable, and the participant is not neurologically impaired.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (22)

Wichita Urology Group PA

Wichita, Kansas, 67226, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Novartis Investigative Site

Camperdown, New South Wales, 2050, Australia

RECRUITING

Novartis Investigative Site

Wollongong, New South Wales, 2500, Australia

RECRUITING

Novartis Investigative Site

Guangzhou, 510060, China

RECRUITING

Novartis Investigative Site

Créteil, 94010, France

RECRUITING

Novartis Investigative Site

Lille, 59020, France

RECRUITING

Novartis Investigative Site

Nantes, 44093, France

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

Hong Kong, 999077, Hong Kong

RECRUITING

Novartis Investigative Site

Budapest, H-1083, Hungary

RECRUITING

Novartis Investigative Site

Szeged, 6725, Hungary

RECRUITING

Novartis Investigative Site

Rozzano, MI, 20089, Italy

RECRUITING

Novartis Investigative Site

Verona, VR, 37134, Italy

RECRUITING

Novartis Investigative Site

Seoul, 05505, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 06591, South Korea

RECRUITING

Novartis Investigative Site

Majadahonda, Madrid, 28222, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28034, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28040, Spain

RECRUITING

Novartis Investigative Site

Ankara, Sihhiye-Altindag, 06230, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Bulbo-Spinal Atrophy, X-Linked

Interventions

darolutamide; abiraterone

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I (Part 1 and Part 2) = Open-label Phase II = Randomized

Study Record Dates

• First Submitted: September 16, 2025
• First Posted: September 24, 2025
• Study Start: January 13, 2026
• Primary Completion (Estimated): August 2, 2032
• Study Completion (Estimated): August 2, 2032
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); KR (2); HK (1); CN (1); ES (3); US (4); TU (1); DE (1); IT (2); HU (2); FR (3)