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)

NCT ID: NCT07190300

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-13
• Study Completion Date: 2032-06-04

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).

Detailed Description

The study consists of two phases:

1. 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 the groups. Participants in both Group A and Group B will continue androgen deprivation therapy (ADT) to maintain castrate testosterone levels (< 50 ng/dL or < 1.7 nmol/L), with the ADT modality determined by the investigator based on local guidelines. In Group B, abiraterone will be co-administered with an oral corticosteroid (prednisone or prednisolone) as per local prescribing information.

2. The Phase II part is a randomized, open-label, multicenter dose-expansion study designed to further evaluate the recommended dose(s) of tulmimetostat in combination with darolutamide and provide proof-of-concept for its efficacy and safety. Participants in Phase II will be randomized to receive either tulmimetostat plus darolutamide or darolutamide alone. Eligible participants include those with de novo or recurrent mHSPC who have not previously received prior radioligand therapy but may have prior exposure to taxane-based chemotherapy and/or androgen receptor pathway inhibitors (ARPI, excluding darolutamide). This study aims to explore tulmimetostat-based combinations as potential therapeutic 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.

Conditions

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Phase I: Group A (part 1)

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

Group Type: EXPERIMENTAL

Tulmimetostat

Intervention Type: DRUG

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

Darolutamide

Intervention Type: DRUG

600 mg is administered orally BID

Phase I: Group B (part 2)

Tulmimetostat PO QD escalating doses + Abiraterone 1000 mg PO QD

Group Type: EXPERIMENTAL

Tulmimetostat

Intervention Type: DRUG

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

Abiraterone

Intervention Type: DRUG

abiraterone 1000 mg is administered orally QD

Phase II: Arm 1

Tulmimetostat dose 1 PO + Darolutamide 600 mg PO BID

Group Type: EXPERIMENTAL

Tulmimetostat

Intervention Type: DRUG

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

Darolutamide

Intervention Type: DRUG

600 mg is administered orally BID

Phase II: Arm 2

Tulmimetostat dose 2 PO + Darolutamide 600 mg PO BID

Group Type: EXPERIMENTAL

Tulmimetostat

Intervention Type: DRUG

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

Darolutamide

Intervention Type: DRUG

600 mg is administered orally BID

Phase II: Arm 3

Darolutamide 600 mg PO BID

Group Type: ACTIVE_COMPARATOR

Darolutamide

Intervention Type: DRUG

600 mg is administered orally BID

Interventions

Tulmimetostat

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

Intervention Type: DRUG

Darolutamide

600 mg is administered orally BID

Intervention Type: DRUG

Abiraterone

abiraterone 1000 mg is administered orally QD

Intervention Type: DRUG

Other Intervention Names

DZR123

Eligibility Criteria

Inclusion Criteria

• Adult men ≥ 18 years old with de novo or recurrent mHSPC (without neuroendocrine or small cell features), with at least one documented metastatic lesion. This lesion 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.

• Prior ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide) 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

• 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.
• 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.

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 with PSA levels of ≤ 0.2 ng/mL at the start of study treatment.
• Participants with a history of central nervous system (CNS) metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), are asymptomatic and neurologically stable without corticosteroids. Baseline and subsequent radiological imaging for them must include evaluation 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) 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Wichita Urology Group PA

Wichita, Kansas, United States

Site Status: RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status: RECRUITING

Novartis Investigative Site

Wollongong, New South Wales, Australia

Site Status: RECRUITING

Novartis Investigative Site

Hong Kong, , Hong Kong

Site Status: RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status: RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status: RECRUITING

Countries

United States; Australia; Hong Kong; South Korea

Central Contacts

Novartis Pharmaceuticals

Role: CONTACT

novartis.email@novartis.com

1-888-669-6682

Novartis Pharmaceuticals

Role: CONTACT

novartis.email@novartis.com

+41613241111

Facility Contacts

Tyler Gentry

Role: primary

tgentry@wichitaurology.com

Lindsey Rabon

Role: primary

lindsey.rabon@startresearch.com

843-839-1679

Other Identifiers

2025-521873-15-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDZR123C12101

Identifier Type: -

Identifier Source: org_study_id