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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

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: A Two-part, Phase I Dose Escalation and Expansion Followed by a Randomized, Open-label Multicenter, Phase II Study to Assess the Safety and Efficacy of the Combination of Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide) vs Standard of Care in Patients With Progressive Metastatic Castrate Resistant Prostate Cancer

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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).

Who May Be Eligible (Plain English)

Key Who May Qualify: - 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 Who Should NOT Join This Trial: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

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

Locations (20)

Sarah Cannon Research Institute
Denver, Colorado, United States
Sarah Cannon Research Institute
Jacksonville, Florida, United States
Wichita Urology Group PA
Wichita, Kansas, United States
Mass General Hospital
Boston, Massachusetts, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Novartis Investigative Site
St Leonards, New South Wales, Australia
Novartis Investigative Site
Melbourne, Victoria, Australia
Novartis Investigative Site
Liverpool, Australia
Novartis Investigative Site
Halifax, Nova Scotia, Canada
Novartis Investigative Site
Beijing, China
Novartis Investigative Site
Herlev, Denmark
Novartis Investigative Site
Odense C, Denmark
Novartis Investigative Site
Vejle, Denmark
Novartis Investigative Site
Bordeaux, France
Novartis Investigative Site
Paris, France
Novartis Investigative Site
Paris, France
Novartis Investigative Site
Milan, MI, Italy
Novartis Investigative Site
Kuching, Sarawak, Malaysia
Novartis Investigative Site
Poznan, Poland
Novartis Investigative Site
Singapore, Singapore