Tulmimetostat plus luxdegalutamide for men with progressive metastatic castrate-resistant prostate cancer.

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This open-label Phase I/II trial begins with a dose-escalation (Part 1a) and dose-expansion/optimization (Part 1b) to identify a recommended combination dose of tulmimetostat and JSB462. After a recommended Phase II dose is defined, Part 2 randomizes taxane‑naive men with progressive mCRPC to receive the combination or standard of care, with PSA50 used as the primary efficacy endpoint. The study monitors safety, tolerability, and antitumor activity across dose levels and uses imaging and PSA measurements to document metastatic disease and response. The trial is global and multicenter with planned follow‑up for clinical and biochemical outcomes.

Why it matters

Who can join: the full rules

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.

Where it's running

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

Study contacts

• Study coordinator: Novartis Pharmaceuticals
• Email: novartis.email@novartis.com
• Phone: 1-888-669-6682

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Dual-target PSMA/PSCA CAR-NK Therapy in Advanced Prostate Cancer

  This trial tests ETB-DualNK-01, a dual-target CAR-NK cell therapy, in adults with metastatic castration-resistant prostate cancer to see if it is safe and shows early signs of activity.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.