A Phase 1/2 interventional study of Tulmimetostat DL1 QD and Tulmimetostat DL2 QD in Progressive Metastatic Castrate Resistant Prostate Cancer, sponsored by Novartis Pharmaceuticals. Recruiting at 35 sites in 14 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-09.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 1/2, Interventional, and Treatment
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).
The Phase 1 study, comprised of Parts 1a and 1b, aims to assess the safety and tolerability of the combination of tulmimetostat and JSB462:
The purpose of the Phase II study (Part 2) is to compare the combination of tulmimetostat with JSB462 in terms of the biochemical response as assessed by PSA50 compared to the standard of care (SoC) in adult men with progressive, taxane-naive mCRPC.
7,046 studies on the registry are indexed under Prostatic Neoplasms; 1,580 are open to participants now.
This study's planned enrollment of 188 is above the median of 60 across 5,348 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Prior ARPI therapy:
Prior chemotherapy:
Key Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Tulmimetostat DL1 QD + JSB462 Dose 1 QD
Drug: Tulmimetostat DL1 QD · Drug: JSB462 Dose 1 QD
Tulmimetostat DL1 QD + JSB462 Dose 2 QD
Drug: Tulmimetostat DL1 QD · Drug: JSB462 Dose 2 QD
Tulmimetostat DL2 QD + JSB462 Dose 1 QD
Drug: Tulmimetostat DL2 QD · Drug: JSB462 Dose 1 QD
Tulmimetostat DL2 QD + JSB462 Dose 2 QD
Drug: Tulmimetostat DL2 QD · Drug: JSB462 Dose 2 QD
Tulmimetostat DL3 QD + JSB462 Dose 1 QD
Drug: Tulmimetostat DL3 QD · Drug: JSB462 Dose 1 QD
Tulmimetostat DL3 QD + JSB462 Dose 2 QD
Drug: Tulmimetostat DL3 QD · Drug: JSB462 Dose 2 QD
Tulmimetostat Dose 1 QD + JSB462 QD
Drug: Tulmimetostat Doses 1 or 2 QD · Drug: JSB462 QD
Tulmimetostat Dose 2 QD + JSB462 QD
Drug: Tulmimetostat Doses 1 or 2 QD · Drug: JSB462 QD
Tulmimetostat RP2D QD + JSB462 QD
Drug: Tulmimetostat RP2D QD · Drug: JSB462 QD
Standard of Care at the discretion of the investigator
Drug: Standard of Care (SoC)
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))
Also known as: DZR123
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))
Also known as: DZR123
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))
Also known as: DZR123
Part 1b (dose expansion and optimization): tulmimetostat doses 1 or 2 QD
Also known as: DZR123
Part 2: tulmimetostat Recommended Phase 2 Dose (RP2D) QD
Also known as: DZR123
JSB462 Dose 1 QD
Also known as: luxdegalutamide
JSB462 Dose 2 QD
Also known as: luxdegalutamide
The dose of JSB462 QD will be determined based on the totality of data from Part 1a
Also known as: luxdegalutamide
Androgen Receptor Pathway Inhibitors (ARPI), chemotherapy or Pluvicto (AAA617) at the discretion of the investigator
Part 1a: Dose-limiting toxicities (DLTs)
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).
Time frame: Up to 28 days
Part 1a and Part 1b: 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.
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 14 months
Part 1a and Part 1b: Number of Participants with dose adjustments
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 14 months
Part 1a and Part 1b: 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
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 14 months
Part 1a and Part 1b: Duration of exposure to each study drug
The duration of exposure (in months) to Tulmimetostat and JSB462 (Part 1a and Part 1b) will be summarized by means of descriptive statistics
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 14 months
Part 1b and Part 2: prostate-specific antigen 50 (PSA50) at 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.
Time frame: Month 6
Part 1a and Part 1b: Plasma concentrations of tulmimetostat and JSB462
Tulmimetostat and JSB462 pharmacokinetic (PK) samples will be obtained and evaluated in all participants at all dose levels by treatment arms
Time frame: Cycle 1-2: Day 1 (predose/0 hour, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours; Tulmimetostat only: 30 minutes and 3 hours). Cycle 1: Day 2 (24 hours), Days 8 and 15 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.
Part 2: Plasma concentrations of tulmimetostat and JSB462
Tulmimetostat and JSB462 pharmacokinetic (PK) samples will be obtained and evaluated in all participants at all dose levels by treatment arms
Time frame: Cycle 1 and 2: Day 1 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.
Part 1a and Part 1b: AUC of tulmimetostat and JSB462
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) and Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) will be listed and summarized using descriptive statistics.
Time frame: Cycle 1-2: Day 1 (predose/0 hour, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours; Tulmimetostat only: 30 minutes and 3 hours). Cycle 1: Day 2 (24 hours), Days 8 and 15 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.
Part 2: AUC of tulmimetostat and JSB462
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) and Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) will be listed and summarized using descriptive statistics.
Time frame: Cycle 1 and 2: Day 1 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.
Part 1a and Part 1b: Cmax of tulmimetostat and JSB462
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Time frame: Cycle 1-2: Day 1 (predose/0 hour, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours; Tulmimetostat only: 30 minutes and 3 hours). Cycle 1: Day 2 (24 hours), Days 8 and 15 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.
Part 2: Cmax of tulmimetostat and JSB462
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Time frame: Cycle 1 and 2: Day 1 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.
Part 1b and Part 2: prostate-specific antigen 50 (PSA50) at 3, 9, and 12 months
PSA50 is defined as a PSA reduction of at least 50% from baseline at 3, 9, and 12 months confirmed by a second PSA measurement ≥ 3 weeks later.
Time frame: Month 3, Month 9, Month 12
Part 1b and Part 2: radiographic progression free survival (rPFS)
rPFS is defined as time between randomization and the first occurrence of disease progression as per PCWG3-modified RECIST v1.1 or death due to any cause
Time frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
Part 1b and Part 2: overall survival (OS)
OS is defined as the time between randomization to date of death due to any cause
Time frame: From date of randomization until date of death from any cause, assessed up to approximately 15 months
Part 1b and Part 2: objective response (OR)
OR is defined as a confirmed complete response (CR) or partial response (PR) per PCWG3-modified RECIST 1.1 as assessed by the investigator
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 15 months
Part 1b and Part 2: best overall response (BOR)
BOR is defined as the best response per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1 as assessed by the Investigator
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 15 months
Part 1b and Part 2: duration of response (DOR)
DOR is defined as time between first documented CR/PR and disease progression or death due to any cause per PCWG3-modified RECIST 1.1 as assessed by the investigator
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 15 months
Part 1b and Part 2: time to first symptomatic skeletal event (TTSSE)
TTSSE is defined as 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.
Time frame: From randomization until the first occurrence of a new symptomatic bone fracture, spinal cord compression, tumor-related orthopedic surgery, radiation therapy for bone pain, or death, assessed up to 15 months.
Part 2: 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.
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 15 months
Part 2: Number of Participants with dose adjustments
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 15 months
Part 2: 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
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 15 months
Part 2: Duration of exposure to each study drug
The duration of exposure (in months) to Tulmimetostat and JSB462 / Standard of Care (SoC) of investigator's choice (Part 2) will be summarized within each strata by means of descriptive statistics
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 15 months
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
No publications or documents are linked to this record.
Started Oct 2025 (actual). Primary completion is estimated for Nov 2029, 48 months after the start.
Of 96 industry-sponsored phase 1/2 interventional studies under Prostatic Neoplasms, half reached primary completion within 52 months of starting (the median), counting those still running; a quarter within 35. This study's planned 48 months is close to that.
Counting every sponsor, half of 210 studies reached it within 61 months; a quarter within 30 and three quarters within 85.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
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Studies of the drug tested here: Tulmimetostat