TulmiSTAR-02: A Phase I/II Open-label Study of Tulmimetostat in Combination With Darolutamide vs. Darolutamide, and Tulmimetostat With Abiraterone in Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
TulmiSTAR-02: A Two-part Phase I Dose Escalation Study of Tulmimetostat (DZR123) in Combination With Darolutamide or Abiraterone Followed by Open-label, Randomized, Phase II Dose Expansion Study to Assess the Safety and Efficacy of Tulmimetostat in Combination With Darolutamide Versus Darolutamide Alone in Patients With Metastatic Hormone-sensitive Prostate Cancer
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests tulmimetostat with darolutamide or abiraterone in men with prostate cancer that has spread and still responds to hormone treatment. It checks safe doses, side effects, and how well the treatments work. Part of the study compares tulmimetostat plus darolutamide with darolutamide alone.
The purpose of this study is to evaluate the safety, tolerability, and efficacy of two different treatment combinations of tulmimetostat in participants with de novo or recurrent metastatic hormone-sensitive prostate cancer (mHSPC). Phase I aims to determine the recommended dose(s) for expansion (RDE) of tulmimetostat in combination with darolutamide or abiraterone. Phase II is designed to further evaluate the efficacy and safety of tulmimetostat in combination with darolutamide compared with darolutamide alone in participants with mHSPC.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Men age 18 or older with newly found or returning prostate cancer that has spread and still responds to hormone treatment. Certain cancer types called neuroendocrine or small cell are not allowed.
- Testosterone level of 50 ng/dL or less.
- Able to care for yourself and be out of bed or a chair for at least half of waking hours.
- Blood cell production and organs must work well enough for treatment.
- Started androgen deprivation therapy (ADT), which lowers testosterone, 28 days to 12 months before joining. You must keep taking it during treatment.
- One past taxane chemotherapy treatment is allowed if the cancer did not worsen during it. In Phase II, only 25% of participants may have had it.
- Past use of an androgen receptor pathway inhibitor (ARPI), a hormone-blocking drug, may be allowed. Phase II allows up to 4 months of use for cancer that has spread, but not current darolutamide use. Switching from a current ARPI requires poor PSA control or trouble taking the drug, without cancer becoming resistant to hormone treatment.
- Past prostate radiation or surgery is allowed. Radiation must be finished before joining, and surgery must have been at least 2 weeks earlier.
Who can't join
- Cancer that has become resistant to testosterone-lowering treatment, or disease found only through rising PSA without known spread. PSA is a blood marker used to track prostate cancer.
- PSA of 0.5 ng/mL or less if you have not used an ARPI for cancer that has spread, or 0.2 ng/mL or less if you have.
- Cancer spread to the brain or spinal cord, unless treated and stable without symptoms. You must not need steroids to control nerve symptoms and must have brain scans.
- Current use of older hormone blockers, such as bicalutamide, or ketoconazole to treat prostate cancer. Brief past use of an older hormone blocker when starting ADT may be allowed.
- Past radioligand therapy, which delivers radiation to cancer cells, or past PRC2-blocking drugs, which block certain proteins.
- Recent use of an experimental drug: within 28 days, or longer if the drug takes more time to leave your body.
- Herbs that may lower PSA within 4 weeks before treatment or during the study. Other banned drugs or herbs must be stopped within the study's required time.
- Certain other current or past cancers. Some treated cancers or cancers in complete remission are allowed, but past leukemia, lymphoma, or myelodysplastic syndrome (a bone marrow disease) is not.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Key Inclusion Criteria: * Adult men ≥ 18 years old with de novo or recurrent mHSPC (without neuroendocrine or small cell features). The tumor lesion(s) may be located in the bone, soft tissue/visceral region, or both. * Participants must have castrate levels of testosterone, i.e., ≤ 50 ng/dL (≤ 1.7 nM). * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Adequate bone marrow and organ function * Prior ADT: Participants must have started ADT at least 1 month (at least 28 days) but no more than 12 months before study entry and be willing to continue ADT during treatment * Prior taxane use for mHSPC is permitted: * Phase I and II: Participants may have received, but not progressed on, one prior taxane-based therapy. * Phase II: Limited to 25% participants with prior taxane use. * Prior ARPI is allowed in both Phase I and Phase II: * Prior ARPI use in biochemical recurrence (BCR) or curative treatment is allowed for any duration, provided therapy was discontinued and participant had no evidence of conventional imaging positive metastatic disease at that time * Prior ARPI use in mHSPC is permitted but not mandated. If participants meet all study eligibility criteria, they are required to stop their prior ARPI after providing informed consent and remain off ARPI until Cycle 1 Day 1, when study treatment is initiated. * Phase I: Allowed for any duration. * Phase II: Allowed prior exposure to ARPI is ≤4 months. Participants with ongoing use of darolutamide are not eligible. Participants with ongoing ARPI are eligible for a switch from their ongoing ARPI therapy if they have not progressed to CRPC disease, and meet any of the criteria, indicative of suboptimal biochemical response, or intolerability, as assessed by the Investigator: * Evidence of insufficient PSA control or suboptimal PSA response, defined as PSA ≥ 0.2 ng/mL after 6-12 months ADT and no more than 4 months of current ARPI therapy in mHSPC with declining or stable PSA trend. Eligibility based on biochemical progression should be supported by objective evidence (e.g. PSA results). * Intolerance and non-compliance: Participant's inability to tolerate or comply with the prescribed ARPI. The site should maintain documentation to support the appropriateness of therapy changes resulting from intolerance or non-compliance. • Other permitted prior local therapy for mHSPC: * Phase I and II: Prior prostate-directed radiation or surgical intervention. Radiation must be completed before study entry; surgery at least 2 weeks prior. Key Exclusion Criteria: * 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 the start of study treatment. * Participants who have not received ARPI treatment for mHSPC and present with PSA levels of ≤0.5 ng/mL or those with prior/ongoing ARPI treatment presenting with PSA levels of ≤ 0.2 ng/mL prior to treatment assignment/randomization. * Participants with CNS metastases are excluded unless: * they have received prior therapy (e.g. surgery, radiotherapy, gamma knife), are neurologically stable and asymptomatic. * they are not receiving corticosteroid for the purpose of maintaining neurologic integrity and have baseline and subsequent radiological imaging of the brain. * Concurrent use of first-generation anti-androgens (like bicalutamide). Prior use of a first-generation anti-androgen drug in the context of ADT initiation with a GNRH analog is allowed, provided it was administered for ≤14 days and the last dose was administered ≥7 days from the study entry. * Systemic ketoconazole is used as antineoplastic treatment for prostate cancer. * Previous exposure to radioligand therapy. * Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry. * Previous treatment with any Polycomb Repressive Complex 2 (PRC2) inhibitor, including but not limited to Enhancer of Zeste Homolog 2 (EZH2) inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors. * Herbal products that may decrease PSA levels within 4 weeks prior to the start of study drug treatment and while on study. * Participants taking prohibited medication(s) (e.g., strong CYP3A4 inducers or strong or moderate CYP3A4 inhibitors that cannot be stopped within 7 days or 5 half-lives (whichever is longer) prior to study treatment and for the duration of the study treatment or prohibited herbal product(s) that cannot be stopped 7 days prior to study treatment. * Have a history of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years. Participants with a history of leukemia/lymphoma and/or MDS are not eligible. Other inclusion/exclusion criteria may apply
Study sites (8)
AL
- Univ of Alabama at Birmingham · Birmingham, AL 35294-3300Luke Hanna · Study contact · lukehanna@uabmc.eduJoelle Hamilton · Principal investigatorMore trials in Birmingham
IA
- Uni Of Iowa Hospitals And Clinics · Iowa City, IA 52242Kerri Fitch · Study contact · kerri-fitch@uiowa.eduFernando Maciel Barbosa · Principal investigatorMore trials in Iowa City
KS
- University of Kansas Cancer Center · Westwood, KS 66205Katie Looney · Study contact · klooney2@kumc.eduHaoran Li · Principal investigatorMore trials in Westwood
- Wichita Urology Group PA · Wichita, KS 67226Tyler Gentry · Study contact · tgentry@wichitaurology.comTimothy Richardson · Principal investigatorMore trials in Wichita
NC
- Duke University Medical Center · Durham, NC 27710Tykeytra Dale · Study contact · tykeytra.dale@duke.eduJeffrey Shevach · Principal investigatorMore trials in Durham
SC
- Medical University of South Carolina MUSC · Charleston, SC 29425Renee Tucker · Study contact · 843-792-7560 · tuckerr@musc.eduKevin Becker · Principal investigatorMore trials in Charleston
- Carolina Urologic Research Center · Myrtle Beach, SC 29572Lindsey Rabon · Study contact · 843-839-1679 · lindsey.rabon@startresearch.comNeal Shore · Principal investigatorMore trials in Myrtle Beach
UT
- Huntsman Cancer Institute · Salt Lake City, UT 84112Alena Turner · Study contact · alena.turner@hci.utah.eduNeeraj Agarwal · Principal investigatorMore trials in Salt Lake City