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)

NCT07206056 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CDZR123A121072025-521880-10-00
• Study Type: interventional
• Target: 188
• Locations: 13 countries
• Sites: 29

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

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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).

  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.

  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.

  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

  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

  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.

  Month 6

Secondary Outcomes (17)

• Part 1a and Part 1b: Plasma concentrations of tulmimetostat and JSB462

  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

  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

  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

  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

  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.

Study Arms (10)

Part 1a: Cohort DL1A

EXPERIMENTAL

Tulmimetostat DL1 QD + JSB462 Dose 1 QD

Drug: Tulmimetostat DL1 QD; Drug: JSB462 Dose 1 QD

Part 1a: Cohort DL1B

EXPERIMENTAL

Tulmimetostat DL1 QD + JSB462 Dose 2 QD

Drug: Tulmimetostat DL1 QD; Drug: JSB462 Dose 2 QD

Part 1a: Cohort DL2A

EXPERIMENTAL

Tulmimetostat DL2 QD + JSB462 Dose 1 QD

Drug: Tulmimetostat DL2 QD; Drug: JSB462 Dose 1 QD

Part 1a: Cohort DL2B

EXPERIMENTAL

Tulmimetostat DL2 QD + JSB462 Dose 2 QD

Drug: Tulmimetostat DL2 QD; Drug: JSB462 Dose 2 QD

Part 1a: Cohort DL3A

EXPERIMENTAL

Tulmimetostat DL3 QD + JSB462 Dose 1 QD

Drug: Tulmimetostat DL3 QD; Drug: JSB462 Dose 1 QD

Part 1a: Cohort DL3B

EXPERIMENTAL

Tulmimetostat DL3 QD + JSB462 Dose 2 QD

Drug: Tulmimetostat DL3 QD; Drug: JSB462 Dose 2 QD

Part 1b : Arm A

EXPERIMENTAL

Tulmimetostat Dose 1 QD + JSB462 QD

Drug: Tulmimetostat Doses 1 or 2 QD; Drug: JSB462 QD

Part 1b: Arm B

EXPERIMENTAL

Tulmimetostat Dose 2 QD + JSB462 QD

Drug: Tulmimetostat Doses 1 or 2 QD; Drug: JSB462 QD

Part 2: Arm 1

EXPERIMENTAL

Tulmimetostat RP2D QD + JSB462 QD

Drug: Tulmimetostat RP2D QD; Drug: JSB462 QD

Part 2: Arm 2

ACTIVE COMPARATOR

Standard of Care at the discretion of the investigator

Drug: Standard of Care (SoC)

Interventions

Tulmimetostat DL1 QD DRUG

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: Cohort DL1A; Part 1a: Cohort DL1B

Tulmimetostat DL2 QD DRUG

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: Cohort DL2A; Part 1a: Cohort DL2B

Tulmimetostat DL3 QD DRUG

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: Cohort DL3A; Part 1a: Cohort DL3B

Tulmimetostat Doses 1 or 2 QD DRUG

Part 1b (dose expansion and optimization): tulmimetostat doses 1 or 2 QD

Also known as: DZR123

Part 1b : Arm A; Part 1b: Arm B

Tulmimetostat RP2D QD DRUG

Part 2: tulmimetostat Recommended Phase 2 Dose (RP2D) QD

Also known as: DZR123

Part 2: Arm 1

JSB462 Dose 1 QD DRUG

JSB462 Dose 1 QD

Also known as: luxdegalutamide

Part 1a: Cohort DL1A; Part 1a: Cohort DL2A; Part 1a: Cohort DL3A

JSB462 Dose 2 QD DRUG

JSB462 Dose 2 QD

Also known as: luxdegalutamide

Part 1a: Cohort DL1B; Part 1a: Cohort DL2B; Part 1a: Cohort DL3B

JSB462 QD DRUG

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

Also known as: luxdegalutamide

Part 1b : Arm A; Part 1b: Arm B; Part 2: Arm 1

Standard of Care (SoC) DRUG

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

Part 2: Arm 2

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Adult men with metastatic castrate resistant prostate cancer (mCRPC)
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (29)

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

RECRUITING

Sarah Cannon Research Institute

Jacksonville, Florida, 32256, United States

RECRUITING

Wichita Urology Group PA

Wichita, Kansas, 67226, United States

RECRUITING

Mass General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

RECRUITING

Novartis Investigative Site

St Leonards, New South Wales, 2065, Australia

RECRUITING

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

RECRUITING

Novartis Investigative Site

Liverpool, 2170, Australia

RECRUITING

Novartis Investigative Site

Halifax, Nova Scotia, B3H 2Y9, Canada

RECRUITING

Novartis Investigative Site

Beijing, 100021, China

RECRUITING

Novartis Investigative Site

Herlev, DK-2730, Denmark

RECRUITING

Novartis Investigative Site

Odense C, 5000, Denmark

RECRUITING

Novartis Investigative Site

Vejle, DK-7100, Denmark

RECRUITING

Novartis Investigative Site

Bordeaux, 33076, France

RECRUITING

Novartis Investigative Site

Paris, 75015, France

RECRUITING

Novartis Investigative Site

Paris, 75231, France

RECRUITING

Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Novartis Investigative Site

Milan, MI, 20133, Italy

RECRUITING

Novartis Investigative Site

Padova, PD, 35128, Italy

RECRUITING

Novartis Investigative Site

Orbassano, TO, 10043, Italy

RECRUITING

Novartis Investigative Site

Kuching, Sarawak, 93586, Malaysia

RECRUITING

Novartis Investigative Site

Poznan, 60-192, Poland

RECRUITING

Novartis Investigative Site

Singapore, 119074, Singapore

RECRUITING

Novartis Investigative Site

Singapore, S308433, Singapore

RECRUITING

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

RECRUITING

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28009, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28041, Spain

RECRUITING

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

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

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1a (dose escalation): Participants will be assigned to cohorts to receive study treatment (tulmimetostat and JSB462) at different provisional dose levels. Part 1b (dose expansion and optimization): Participants will be randomized in a ratio and receive study treatment as: * Arm A: Tulmimetostat Dose 1 QD + JSB462 QD * Arm B: Tulmimetostat Dose 2 QD + JSB462 QD Part 2: Participants will be randomized in a ratio and receive study treatment as: * Arm 1: Tulmimetostat RP2D QD + JSB462 (either Dose 1 or Dose 2 QD) * Arm 2 (Control): SoC (ARPI, chemotherapy, Pluvicto) at the discretion of the investigator

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: October 3, 2025
• Study Start: October 15, 2025
• Primary Completion (Estimated): November 9, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); DE (1); DK (3); FR (3); SG (2); CN (1); ES (4); CA (1); US (5); IT (3); PL (1); GB (1); MY (1)