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

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

Phase1; Phase2 Interventional Novartis · NCT07206056

This will test whether combining tulmimetostat (DZR123) with luxdegalutamide (JSB462) helps men with progressive metastatic castrate-resistant prostate cancer achieve better PSA responses than standard care.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment188 (estimated)
Ages18 Years and up
SexMale
SponsorNovartis Industry-sponsored
Drugs / interventionschemotherapy
Locations30 sites (Denver, Colorado and 29 other locations)
Trial IDNCT07206056 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Adult men with progressive metastatic castrate‑resistant prostate cancer who have castrate testosterone levels, at least one metastatic lesion on imaging, and prior progression on a second‑generation androgen receptor pathway inhibitor are the intended participants.

Not a fit: Men with neuroendocrine or small‑cell prostate cancer features, those who are not castrate, have uncontrolled comorbidities, or cannot attend a participating site are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could increase PSA response rates and delay disease progression compared with current standard therapies.

How similar studies have performed: Some prior combinations targeting the androgen receptor pathway and novel agents have shown promise, but this specific tulmimetostat plus JSB462 combination is novel and not yet proven in later‑stage trials.

Eligibility criteria

Show full inclusion / 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.

Where this trial is running

Denver, Colorado and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Progressive Metastatic Castrate Resistant Prostate Cancermetastatic castrate resistant prostate cancertulmimetostatluxdegalutamideAndrogen Deprivation TherapyStandard of careTulmiSTAR-01
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.