TULMIMETOSTAT for Metastatic hormone-sensitive prostate cancer

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants must have castrate levels of testosterone, i.e., ≤ 50 ng/dL (≤ 1.7 nM)"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2"}
• {"criterion_text":"- Adequate bone marrow and organ function"}
• {"criterion_text":"- Prior ADT: Participants must have started androgen deprivation therapy (ADT) at least 1 month but no more than 24 months before study entry and be willing to continue ADT during treatment"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Prior ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide) is allowed in both Phase I and Phase II: a. 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 b. 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."}
• {"criterion_text":"- 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

• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants with PSA levels of ≤ 0.2 ng/mL at the start of study treatment"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Systemic ketoconazole is used as antineoplastic treatment for prostate cancer."}
• {"criterion_text":"- Previous exposure to radioligand therapy."}
• {"criterion_text":"- Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Herbal products that may decrease PSA levels within 4 weeks prior to the start of study drug treatment and while on study"}

Primary endpoints

• {"endpoint_text":"- Phase I - Safety: DLTs during the first 28 days of combination treatment. Type, frequency and severity of AEs per CTCAE v5.0 and notable values in laboratory values, vital signs, and ECGs - Tolerability: Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to study treatment (all study drugs) Phase II: BCR defined as PSA decline to < 0.2 ng/mL at 6 months, confirmed by a second PSA measurement ≥ 3 weeks later","definition_or_measurement_approach":"Phase I safety measured as dose-limiting toxicities (DLTs) during first 28 days; AEs graded by CTCAE v5.0; laboratory, vital signs, ECG abnormalities noted. Tolerability by dose interruptions/reductions/discontinuations, dose intensity and exposure duration. Phase II primary efficacy (BCR) defined as PSA decline to <0.2 ng/mL at 6 months, confirmed by a second PSA measurement at least 3 weeks later."}

Secondary endpoints

• {"endpoint_text":"- Phase I: Plasma concentrations of tulmimetostat, darolutamide, and abiraterone, and derived PK parameters including AUC and Cmax Phase II: Radiographic progression free survival (rPFS), Overall survival (OS), Objective response (OR), Best overall response (BOR), Duration of response (DOR), PSA50 and Biochemical Response of <0.1 ng/mL, Time to castration–resistant prostate cancer (CRPC)","definition_or_measurement_approach":"Phase I PK: plasma concentrations and derived PK parameters (AUC, Cmax). Phase II: standard oncology efficacy endpoints measured by radiographic assessments for rPFS, OS by survival follow-up, objective and best overall response by radiographic/RECIST or relevant criteria, DOR measured from response to progression, PSA50 and biochemical response <0.1 ng/mL, time to CRPC recorded."}
• {"endpoint_text":"- Phase II: - Safety: Type, frequency and severity of treatment-emergent and treatment-related AEs per CTCAE version 5.0 and notable values in laboratory parameters, vital signs and ECGs - Tolerability: Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to study treatment (all study drugs)","definition_or_measurement_approach":"Safety assessed by type/frequency/severity of treatment-emergent and treatment-related AEs per CTCAE v5.0 and significant laboratory/vital sign/ECG changes. Tolerability assessed by dose interruptions, reductions, discontinuations, dose intensity and exposure duration across study drugs."}
• {"endpoint_text":"- Phase II: Plasma concentrations of tulmimetostat and darolutamide.","definition_or_measurement_approach":"Plasma PK sampling to determine concentrations of tulmimetostat and darolutamide during Phase II."}
• {"endpoint_text":"- Phase II: TTSSE defined as the time from randomization to the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first","definition_or_measurement_approach":"TTSSE measured as time from randomization to first occurrence of symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgery, need for radiation for bone pain, or death (first event counts)."}

France

Earliest CTIS Part Ii Submission Date

08-12-2025

Latest Decision Or Authorization Date

18-12-2025

Processing Time Days

10

Number Of Sites

6

Number Of Participants

16

Germany

Earliest CTIS Part Ii Submission Date

04-12-2025

Latest Decision Or Authorization Date

19-12-2025

Processing Time Days

15

Number Of Sites

2

Number Of Participants

10

Hungary

Earliest CTIS Part Ii Submission Date

04-12-2025

Latest Decision Or Authorization Date

18-12-2025

Processing Time Days

14

Number Of Sites

4

Number Of Participants

7

Spain

Earliest CTIS Part Ii Submission Date

27-10-2025

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

81

Number Of Sites

5

Number Of Participants

16

Italy

Earliest CTIS Part Ii Submission Date

24-10-2025

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

108

Number Of Sites

3

Number Of Participants

5

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA Limited

Responsibilities

sponsor duties codes: 1

Name

Syneos Health Inc.

Responsibilities

sponsor duties codes: 1

Name

Icon Clinical Research Limited

Responsibilities

sponsor duties codes: 1

Name

Parexel International (IRL) Limited

Responsibilities

sponsor duties codes: 12

Third parties

• {"country":"France","full_name":"Creapharm Bioservices","duties_or_roles":"sponsor duties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsor duties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsor duties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsor duties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"sponsor duties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsor duties codes: 12","organisation_type":"Pharmaceutical company"}