Recruiting
Phase 1
Phase 2

Tulmimetostat & JSB462

Sponsor:

Novartis Pharmaceuticals

Code:

NCT07206056

Conditions

Progressive Metastatic Castrate Resistant Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Tulmimetostat DL1 QD

Tulmimetostat DL2 QD

Tulmimetostat DL3 QD

Tulmimetostat Doses 1 or 2 QD

Tulmimetostat RP2D QD

Study Details

Brief summary:

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).

Conditions

Progressive Metastatic Castrate Resistant Prostate Cancer

Study ID

NCT07206056

Start date

Oct 15, 2025

Status verified date

Aug, 2026

Completion date

Dec 1, 2030

Anticipated

Primary completion date

Nov 9, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Key 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.

Study Design

Enrollment

188 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1a: Cohort DL1A

Tulmimetostat DL1 QD + JSB462 Dose 1 QD

experimental: Part 1a: Cohort DL1B

Tulmimetostat DL1 QD + JSB462 Dose 2 QD

experimental: Part 1a: Cohort DL2A

Tulmimetostat DL2 QD + JSB462 Dose 1 QD

experimental: Part 1a: Cohort DL2B

Tulmimetostat DL2 QD + JSB462 Dose 2 QD

experimental: Part 1a: Cohort DL3A

Tulmimetostat DL3 QD + JSB462 Dose 1 QD

experimental: Part 1a: Cohort DL3B

Tulmimetostat DL3 QD + JSB462 Dose 2 QD

experimental: Part 1b : Arm A

Tulmimetostat Dose 1 QD + JSB462 QD

experimental: Part 1b: Arm B

Tulmimetostat Dose 2 QD + JSB462 QD

experimental: Part 2: Arm 1

Tulmimetostat RP2D QD + JSB462 QD

active comparator: Part 2: Arm 2

Standard of Care at the discretion of the investigator

Interventions

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))

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))

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))

Tulmimetostat Doses 1 or 2 QD

Part 1b (dose expansion and optimization):

tulmimetostat doses 1 or 2 QD

Tulmimetostat RP2D QD

Part 2:

tulmimetostat Recommended Phase 2 Dose (RP2D) QD

JSB462 Dose 1 QD

JSB462 Dose 1 QD

JSB462 Dose 2 QD

JSB462 Dose 2 QD

JSB462 QD

The dose of JSB462 QD will be determined based on the totality of data from Part 1a

Standard of Care (SoC)

Androgen Receptor Pathway Inhibitors (ARPI), chemotherapy or Pluvicto (AAA617) at the discretion of the investigator

Primary outcome measure

  • Part 1a: Dose-limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
  • 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 ]
  • 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 ]
  • Part 1a and Part 1b: Dose Intensity [ 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 [ 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 [ Time Frame: Month 6 ]

Central Contacts and Locations

Central contacts

Novartis Pharmaceuticals

1-888-669-6682novartis.email@novartis.com

Novartis Pharmaceuticals

+41613241111novartis.email@novartis.com

Locations

Sarah Cannon Research Institute

Recruiting

Denver, Colorado, United States, 80218

Contacts

Alissa Snow

720-754-2610alissa.snow@sarahcannon.com

Principal Investigator:

Gerald Falchook

Sarah Cannon Research Institute

Recruiting

Jacksonville, Florida, United States, 32256

Contacts

Kandyce Trejo

941-377-9993kandyce.trejo@flcancer.org

Principal Investigator:

Manish Patel

Emory University

Recruiting

Atlanta, Georgia, United States, 30329

Contacts

Wilena Session

404-778-1900wsessio@emory.edu

Principal Investigator:

Jacqueline Brown

Wichita Urology Group PA

Recruiting

Wichita, Kansas, United States, 67226

Contacts

Tyler Gentry

tgentry@wichitaurology.com

Principal Investigator:

Timothy Richardson

Mass General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Manda Ngin

mngin@mgh.harvard.edu

Principal Investigator:

Xin Gao

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Tykeytra Dale

tykeytra.dale@duke.edu

Principal Investigator:

Christopher Hoimes

Cleveland Clinic Foundation

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Chandra Taylor

216-444-0441TAYLORC12@ccf.org

Principal Investigator:

Shilpa Gupta

Fred Hutchinson Cancer Research Center

Recruiting

Seattle, Washington, United States, 98109-1024

Contacts

Ashley Gagnon

206-606-7486agagnon@fredhutch.org

Principal Investigator:

Michael Schweizer

Novartis Investigative Site

Recruiting

Halifax, Nova Scotia, Canada, B3H 2Y9

More Information

Sponsor

Novartis Pharmaceuticals

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Keywords

  • metastatic castrate resistant prostate cancer (mCRPC)
  • tulmimetostat (DZR123)
  • luxdegalutamide (JSB462)
  • Androgen Deprivation Therapy (ADT)
  • Standard of care (SoC)
  • TulmiSTAR-01

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Novartis Pharmaceuticals on 2026-08-21.