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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 · Novartis
In plain English
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Official title
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
About this study
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.
Eligibility 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.
Study design
Enrollment target: 188 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-10-15
Estimated completion: 2030-12-01
Last updated: 2026-06-03
Interventions
Drug: Tulmimetostat DL1 QDDrug: Tulmimetostat DL2 QDDrug: Tulmimetostat DL3 QDDrug: Tulmimetostat Doses 1 or 2 QDDrug: Tulmimetostat RP2D QDDrug: JSB462 Dose 1 QDDrug: JSB462 Dose 2 QDDrug: JSB462 QDDrug: Standard of Care (SoC)
Primary outcomes
- • Part 1a: Dose-limiting toxicities (DLTs) (Up to 28 days)
- • Part 1a and Part 1b: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) (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 (From date of randomization till 30 days safety fup, assessed up to approximately 14 months)
Sponsor
Novartis Pharmaceuticals · industry
Contacts & investigators
ContactNovartis Pharmaceuticals · contact · novartis.email@novartis.com · 1-888-669-6682
ContactNovartis Pharmaceuticals · contact · novartis.email@novartis.com · +41613241111
InvestigatorNovartis Pharmaceuticals · study_director, Novartis Pharmaceuticals
All locations (32)
Sarah Cannon Research InstituteRecruiting
Denver, Colorado, United States
Sarah Cannon Research InstituteRecruiting
Jacksonville, Florida, United States
Emory UniversityRecruiting
Atlanta, Georgia, United States
Wichita Urology Group PARecruiting
Wichita, Kansas, United States
Mass General HospitalRecruiting
Boston, Massachusetts, United States
Fred Hutchinson Cancer Research CenterRecruiting
Seattle, Washington, United States
Novartis Investigative SiteRecruiting
St Leonards, New South Wales, Australia
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Melbourne, Victoria, Australia
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Liverpool, Australia
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Halifax, Nova Scotia, Canada
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Beijing, China
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Herlev, Denmark
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Odense C, Denmark
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Vejle, Denmark
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Bordeaux, France
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Paris, France
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Paris, France
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Düsseldorf, North Rhine-Westphalia, Germany
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Milan, MI, Italy
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Padova, PD, Italy
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Orbassano, TO, Italy
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Kuching, Sarawak, Malaysia
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Tlalpan, Mexico City, Mexico
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Poznan, Poland
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Singapore, Singapore
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Singapore, Singapore
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Santiago Compostela, A Coruna, Spain
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L'Hospitalet de Llobregat, Barcelona, Spain
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Madrid, Spain
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Madrid, Spain
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Sutton, Surrey, United Kingdom
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London, United Kingdom