NCT07206056 · Novartis Pharmaceuticals
An Open-label Dose Escalation and Expansion, Followed by a Phase II Study of Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide) in Patients With Progressive Metastatic Castrate Resistant Prostate Cancer (mCRPC) (TulmiSTAR-01)
(TulmiSTAR-01)
What this study is about
This is a two-part, Phase I/II, where both patients and doctors know the treatment given, global, conducted at multiple hospitals study assessing the safety and effectiveness of the combination of tulmimetostat (DZR123) and JSB462 (luxdegalutamide) versus the usual treatment in participants with progressive metastatic castrate resistant prostate cancer (mCRPC).
View original scientific description
This is a two-part, Phase I/II, open-label, global, multicenter study assessing the safety and efficacy of the combination of tulmimetostat (DZR123) and JSB462 (luxdegalutamide) versus standard of care in participants with progressive metastatic castrate resistant prostate cancer (mCRPC).
Interventions
DRUG
Tulmimetostat DL1 QD
Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s))
DRUG
Tulmimetostat DL2 QD
Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s))
DRUG
Tulmimetostat DL3 QD
Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s))
DRUG
Tulmimetostat Doses 1 or 2 QD
Part 1b (dose expansion and optimization): tulmimetostat doses 1 or 2 QD
DRUG
Tulmimetostat RP2D QD
Part 2: tulmimetostat Recommended Phase 2 Dose (RP2D) QD
DRUG
JSB462 Dose 1 QD
JSB462 Dose 1 QD
DRUG
JSB462 Dose 2 QD
JSB462 Dose 2 QD
DRUG
JSB462 QD
The dose of JSB462 QD will be determined based on the totality of data from Part 1a
DRUG
Standard of Care (SoC)
Androgen Receptor Pathway Inhibitors (ARPI), chemotherapy or Pluvicto (AAA617) at the discretion of the investigator
Primary outcome measures
Part 1a: Dose-limiting toxicities (DLTs)
Time frame: Up to 28 days
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the first 28 days of treatment with tulmimetostat and JSB462 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).
Part 1a and Part 1b: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 14 months
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Part 1a and Part 1b: Number of Participants with dose adjustments
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 14 months
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Part 1a and Part 1b: Dose Intensity
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 14 months
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
Part 1a and Part 1b: Duration of exposure to each study drug
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 14 months
The duration of exposure (in months) to Tulmimetostat and JSB462 (Part 1a and Part 1b) will be summarized by means of descriptive statistics
Part 1b and Part 2: prostate-specific antigen 50 (PSA50) at Month 6
Time frame: Month 6
PSA50 is defined as a PSA reduction of at least 50% from baseline at 6 months confirmed by a second PSA measurement ≥ 3 weeks later.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Participant is an adult man ≥ 18 years of age.
- Participant must have histologically and/or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell features (current or prior biopsy of the prostate and/or metastatic site).
- Participant must have ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to start of treatment (Part 1a dose escalation) or randomization (Part 1b dose expansion and Part 2).
- Participant must have progressive mCRPC.
- Participant must have a castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
- Prior ARPI therapy:
- Part 1a and 1b only: must have progressed on at least one prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide).
- Part 2 only: must have progressed on one prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide).
- Prior chemotherapy:
- Part 1a dose escalation only: may have received ≤ 2 prior lines of chemotherapy in CRPC setting. Note: Prior chemotherapy is permitted in the HSPC setting.
- Part 1b dose expansion/optimization only: may have received up to one prior line of chemotherapy in CRPC setting. Note: Prior chemotherapy is permitted in the HSPC setting.
- Part 2 only: Participants must be taxane-naïve in mCRPC setting; prior chemotherapy permitted in HSPC setting only Key
Exclusion criteria
- Previous treatment with any PRC2 inhibitor, including but not limited to EZH2 inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors.
- Previous treatment with a protein degrader compound that targets the AR.
- Known hypersensitivity or contraindication to any of the study treatment components or its excipients or to drugs of similar chemical classes.
- Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.
- Previous treatment with radioligand therapy in the mCRPC setting, except in Part 1a where participants may have received RLT in mCRPC setting.
- 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 study entry.
- Participants with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purpose of maintaining neurologic integrity. Those with leptomeningeal disease are eligible if those areas have been treated, are stable, and no neurological impairment is present. For those with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain with MRI (preferred) or CT with contrast. Other protocol-defined inclusion/exclusion criteria may apply.
Where
- Denver, Colorado
- Jacksonville, Florida
- Atlanta, Georgia
- Wichita, Kansas
- Boston, Massachusetts
- Durham, North Carolina
- Cleveland, Ohio
- Seattle, Washington
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Aug 21, 2026 · Source of record for eligibility and locations