Tulmimetostat + JSB462 for Prostate Cancer

(TulmiSTAR-01 Trial)

Recruiting at 5 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Second generation ARPI

Must not be taking: PRC2 inhibitors, Protein degraders

Disqualifiers: CNS metastases, Hypersensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

188 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for men with progressive metastatic castrate-resistant prostate cancer (mCRPC). The study aims to evaluate the safety and effectiveness of combining two drugs, tulmimetostat (DZR123) and JSB462 (Luxdegalutamide), compared to standard treatments. Different groups receive various doses to identify the best option. Men with confirmed prostate cancer that has spread and continues to progress despite previous treatments may be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that both tulmimetostat and JSB462 are generally well-tolerated when used alone. Specifically, doses of 200 mg and 300 mg of tulmimetostat were safe and showed potential in fighting tumors. JSB462, tested with other drugs like abiraterone, also maintained a good safety record.

Research suggests that combining these two drugs results in a manageable safety profile, with most side effects not being severe. However, this trial remains in the early stages, and more data is being collected to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tulmimetostat (DZR123) combined with JSB462 (Luxdegalutamide) for prostate cancer because they bring a novel approach to treatment. Unlike most current therapies that focus on hormone suppression, Tulmimetostat is a new player targeting epigenetic changes, potentially offering a different way to control cancer growth. JSB462, meanwhile, is a promising next-generation androgen receptor antagonist that might work even when traditional treatments become less effective. This combination aims to tackle prostate cancer from multiple angles, potentially improving outcomes for patients with advanced disease.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that the combination of tulmimetostat and JSB462, administered in various dosages to trial participants, may help treat prostate cancer, particularly when standard treatments fail. Tulmimetostat weakens cancer cells by preventing DNA repair, while JSB462 blocks signals that promote prostate cancer growth. Early studies suggest that using these two drugs together might reduce cancer activity, as indicated by lower PSA (prostate-specific antigen) levels, which doctors use to monitor prostate cancer. These initial results offer hope for a new treatment option for those with advanced prostate cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adult men over 18 with metastatic castrate resistant prostate cancer (mCRPC) that has worsened after treatment with specific hormone therapies. They must have at least one detectable metastatic lesion and a low testosterone level. Prior chemotherapy is allowed under certain conditions, but participants cannot have neuroendocrine or small cell features of prostate cancer.

Inclusion Criteria

My prostate cancer is worsening despite treatment.

I have at least one cancer spread that shows on scans taken within the last 28 days.

My testosterone levels are very low (<50 ng/dL or <1.7 nmol/L).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part 1a)

Parallel dose escalation to determine the recommended dose(s) of tulmimetostat and JSB462 in combination

Up to 28 days

Multiple visits for dose escalation and monitoring

Dose Expansion/Optimization (Part 1b)

Dose expansion to determine the recommended dose for Phase II

Up to 14 months

Regular visits for dose optimization and monitoring

Phase II Treatment (Part 2)

Comparison of tulmimetostat and JSB462 combination versus standard of care in terms of biochemical response

Up to 15 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• JSB462 (Luxdegalutamide)
• Tulmimetostat (DZR123)

Trial Overview The study tests the safety and effectiveness of combining two drugs, Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide), compared to standard care in mCRPC patients. It's an open-label global study with dose escalation to find the right doses followed by a phase II comparison.

How Is the Trial Designed?

Group I: Part 2: Arm 1 Experimental Treatment 2 Interventions

Tulmimetostat RP2D QD + JSB462 QD

Group II: Part 1b: Arm B Experimental Treatment 2 Interventions

Tulmimetostat Dose 2 QD + JSB462 QD

Group III: Part 1b : Arm A Experimental Treatment 2 Interventions

Tulmimetostat Dose 1 QD + JSB462 QD

Group IV: Part 1a: Cohort DL3B Experimental Treatment 2 Interventions

Tulmimetostat DL3 QD + JSB462 Dose 2 QD

Group V: Part 1a: Cohort DL3A Experimental Treatment 2 Interventions

Tulmimetostat DL3 QD + JSB462 Dose 1 QD

Group VI: Part 1a: Cohort DL2B Experimental Treatment 2 Interventions

Tulmimetostat DL2 QD + JSB462 Dose 2 QD

Group VII: Part 1a: Cohort DL2A Experimental Treatment 2 Interventions

Tulmimetostat DL2 QD + JSB462 Dose 1 QD

Group VIII: Part 1a: Cohort DL1B Experimental Treatment 2 Interventions

Tulmimetostat DL1 QD + JSB462 Dose 2 QD

Group IX: Part 1a: Cohort DL1A Experimental Treatment 2 Interventions

Tulmimetostat DL1 QD + JSB462 Dose 1 QD

Group X: Part 2: Arm 2 Active Control 1 Intervention

Standard of Care at the discretion of the investigator

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07206056

Study Details | NCT07206056 | An Open-label Dose ... 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 ...

2. novartis.com novartis.com/clinicaltrials/study/nct07206056

An Open-label Dose Escalation and Expansion ... 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 ...

3. prostatewarriors.com prostatewarriors.com/2025/10/13/phase-1-2-study-new-combination-therapy-combines-tulmimetostat-dzr123-and-jsb462-aka-luxdegalutamide-aka-arv-766/

Phase 1/2 Study: New Combination Therapy ... Tulmimetostat impairs the cancer cells' ability to recover from DNA damage, while JSB462 eliminates the androgen receptor signaling that fuels ...

4. sigma.larvol.com sigma.larvol.com/product.php?e1=748185&tab=newstrac

tulmimetostat (DZR123) News Collectively, this data suggests that tulmimetostat has the potential to achieve clinical benefit in solid tumors as a monotherapy but also in combination with ...

5. synapse.patsnap.com synapse.patsnap.com/drug/4b93b28e25b04abbb67e563da8b1a2ff

Luxdegalutamide - Drug Targets, Indications, Patents A Phase II, Randomized, Open-label, Multi-center Study of JSB462 (Luxdegalutamide) in Combination With Abiraterone in Adult Male Patients With Metastatic ...

6. delta.larvol.com delta.larvol.com/Products/?ProductId=63fb5ab7-9e18-4fbb-81b6-90fd872cd019

tulmimetostat (DZR123) / Novartis Tulmimetostat showed an improved and acceptable safety profile in OCCC and EC at 200 mg and 300 mg doses (versus 350 mg) with promising antitumor activity.