TulmiSTAR-02: 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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Feb 2026 → ongoing

Decision date (initial)

2025-12-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

Phase I : To determine the Recommended Dose(s) for Expansion (RDE(s) of tulmimetostat in combination with darolutamide and tulmimetostat in combination with abiraterone
Phase II: To determine the improvement in biochemical response rate (BCR) of tulmimetostat in combination with darolutamide compared to darolutamide alone

Secondary objectives 4

1. · Phase I: To characterize the pharmacokinetics (PK) of tulmimetostat, darolutamide, and abiraterone in combination therapies. · Phase II: To assess the efficacy of tulmimetostat at one or more dose levels in combination with darolutamide, compared to darolutamide alone.
2. Phase II: To evaluate the safety and tolerability of tulmimetostat at one or more doses in combination with darolutamide compared to darolutamide alone
3. Phase II: To further characterize the PK of tulmimetostat and darolutamide in combination therapy
4. Phase II: To evaluate the time to first symptomatic skeletal event (TTSSE) at one or more tulmimetostat doses in combination with darolutamide compared to darolutamide alone

Conditions and MedDRA coding

Metastatic hormone-sensitive prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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.
2. Participants must have castrate levels of testosterone, i.e., ≤ 50 ng/dL (≤ 1.7 nM)
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
4. Adequate bone marrow and organ function
5. 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
6. 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
7. 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.
8. 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 10

1. 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.
2. Participants with PSA levels of ≤ 0.2 ng/mL at the start of study treatment
3. 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
4. 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.
5. Systemic ketoconazole is used as antineoplastic treatment for prostate cancer.
6. Previous exposure to radioligand therapy.
7. Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.
8. 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.
9. Herbal products that may decrease PSA levels within 4 weeks prior to the start of study drug treatment and while on study
10. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 4

1. 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)
2. 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)
3. Phase II: Plasma concentrations of tulmimetostat and darolutamide.
4. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 6

Locations

5 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications