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)

Novartis

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Progressive Metastatic Castrate Resistant Prostate Cancer

Treatments: Drug: Tulmimetostat RP2D QD; Drug: JSB462 QD; Drug: Tulmimetostat DL1 QD; Drug: Tulmimetostat Doses 1 or 2 QD; Drug: Tulmimetostat DL2 QD; Drug: Tulmimetostat DL3 QD; Drug: JSB462 Dose 2 QD; Drug: JSB462 Dose 1 QD; Drug: Standard of Care (SoC)

Study type: Interventional

Funder types: Industry

Identifiers

NCT07206056

CDZR123A12107

2025-521880-10-00 (Registry Identifier)

Details and patient eligibility

About

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).

Full description

The Phase 1 study, comprised of Parts 1a and 1b, aims to assess the safety and tolerability of the combination of tulmimetostat and JSB462:

1. Part 1a is the parallel dose escalation that aims to determine the recommended dose(s) of tulmimetostat and JSB462, in combination, for further exploration.
2. Part 1b is the dose expansion/optimization that aims to determine the recommended dose of the combination for Phase II.

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.

Enrollment: 188 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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188 participants in 10 patient groups

Part 1a: Cohort DL1A

Experimental group

Description:

Tulmimetostat DL1 QD + JSB462 Dose 1 QD

Treatment:

Drug: JSB462 Dose 1 QD

Drug: Tulmimetostat DL1 QD

Part 1a: Cohort DL1B

Experimental group

Description:

Tulmimetostat DL1 QD + JSB462 Dose 2 QD

Treatment:

Drug: JSB462 Dose 2 QD

Drug: Tulmimetostat DL1 QD

Part 1a: Cohort DL2A

Experimental group

Description:

Tulmimetostat DL2 QD + JSB462 Dose 1 QD

Treatment:

Drug: JSB462 Dose 1 QD

Drug: Tulmimetostat DL2 QD

Part 1a: Cohort DL2B

Experimental group

Description:

Tulmimetostat DL2 QD + JSB462 Dose 2 QD

Treatment:

Drug: JSB462 Dose 2 QD

Drug: Tulmimetostat DL2 QD

Part 1a: Cohort DL3A

Experimental group

Description:

Tulmimetostat DL3 QD + JSB462 Dose 1 QD

Treatment:

Drug: JSB462 Dose 1 QD

Drug: Tulmimetostat DL3 QD

Part 1a: Cohort DL3B

Experimental group

Description:

Tulmimetostat DL3 QD + JSB462 Dose 2 QD

Treatment:

Drug: JSB462 Dose 2 QD

Drug: Tulmimetostat DL3 QD

Part 1b : Arm A

Experimental group

Description:

Tulmimetostat Dose 1 QD + JSB462 QD

Treatment:

Drug: Tulmimetostat Doses 1 or 2 QD

Drug: JSB462 QD

Part 1b: Arm B

Experimental group

Description:

Tulmimetostat Dose 2 QD + JSB462 QD

Treatment:

Drug: Tulmimetostat Doses 1 or 2 QD

Drug: JSB462 QD

Part 2: Arm 1

Experimental group

Description:

Tulmimetostat RP2D QD + JSB462 QD

Treatment:

Drug: JSB462 QD

Drug: Tulmimetostat RP2D QD

Part 2: Arm 2

Active Comparator group

Description:

Standard of Care at the discretion of the investigator

Treatment:

Drug: Standard of Care (SoC)