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)

What this study is 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).

Who can join (things the study team will check)

✅ You may be able to join 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 be able to join 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. Other protocol-defined inclusion/exclusion criteria may apply.

Where this trial is running

• Sarah Cannon Research Institute, Denver, Colorado, United States
• Sarah Cannon Research Institute, Jacksonville, Florida, United States
• Emory University, Atlanta, Georgia, United States
• Wichita Urology Group PA, Wichita, Kansas, United States
• Mass General Hospital, Boston, Massachusetts, United States
• Duke University Medical Center, Durham, North Carolina, United States
• Cleveland Clinic Foundation, Cleveland, Ohio, 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

+ 23 more sites.

Who to contact

Novartis Pharmaceuticals · 1-888-669-6682 · novartis.email@novartis.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT07206056.