(R)-9bMS for Prostate Cancer

(PHAROS Trial)

Overseen By Gerald Andriole, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: TechnoGenesys, Inc.

Must be taking: Androgen deprivation therapy

Must not be taking: Kinase inhibitors, Corticosteroids

Disqualifiers: Small cell prostate cancer, Seizures, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new drug, (R)-9bMS, for treating metastatic castration-resistant prostate cancer (CRPC), a form of prostate cancer that resists standard hormone therapies. Animal studies have shown that the drug suppresses tumor growth and enhances the immune response against cancer cells. The trial seeks participants with metastatic CRPC who are on hormone therapy and have experienced tumor progression despite previous treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, helping researchers understand its effects in people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you must continue androgen deprivation therapy (ADT) and cannot have taken certain medications like small molecule kinase inhibitors or anti-androgen agents within 14 days before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that (R)-9bMS is likely to be safe for humans?

Research has shown that (R)-9bMS produced promising results in early studies with mice. It slowed tumor growth that did not respond to treatments like Enzalutamide and Abiraterone and appeared to aid the immune system in fighting cancer. However, as this is a Phase 1 trial, it marks the first time this treatment is tested in humans.

This phase is crucial for assessing the drug's safety and tolerability. The primary goal is to identify any serious side effects that could halt the trial. Additionally, this phase will help determine the appropriate dose for future studies.

Without specific human data, the exact human response to the drug remains unknown. However, moving into human trials indicates reasonable confidence in its potential safety based on animal studies. Researchers will closely monitor participants to gather information on side effects and drug tolerance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about (R)-9bMS for prostate cancer because it offers a novel approach compared to traditional treatments like hormone therapy and chemotherapy. Most existing treatments work by targeting hormones or killing rapidly dividing cells, but (R)-9bMS is unique due to its specific mechanism of action, which is still being elucidated in trials. This new drug could potentially provide a more targeted treatment with fewer side effects, offering hope for improved outcomes in prostate cancer patients who may not respond well to existing therapies. Additionally, the oral administration of (R)-9bMS could improve convenience and quality of life for patients, as it can be taken at home rather than requiring hospital visits for treatment.

What evidence suggests that (R)-9bMS might be an effective treatment for prostate cancer?

Research has shown that the new treatment, (R)-9bMS, could benefit prostate cancer that resists standard treatments. In studies with mice, (R)-9bMS stopped the growth of prostate cancer tumors unresponsive to common drugs like Enzalutamide and Abiraterone. This treatment also aids the immune system in fighting these tumors. Lab tests demonstrated that (R)-9bMS reactivated certain blood cells from patients to attack cancer cells. These findings suggest that (R)-9bMS might offer a new approach for treating prostate cancer that no longer responds to usual treatments. Participants in this trial will receive (R)-9bMS in either a dose escalation or expansion phase to evaluate its effectiveness and safety. ^{1 5 6 7 8}

Who Is on the Research Team?

Douglas McNeel, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for adults with metastatic castration-resistant prostate cancer. Participants must have a confirmed diagnosis and may not have had previous treatments that would conflict with the study drug. The trial excludes individuals who cannot take oral medication or have conditions that could interfere with the study outcomes.

Inclusion Criteria

I am a man who will use two forms of contraception, including a barrier method, during and for 5 months after the study.

My scans show cancer has spread to other parts of my body.

Corrected QT interval calculated by the Fridericia formula (QTcF) ≤ 500 ms (by ECG)

Exclusion Criteria

I do not have any severe ongoing illnesses that are not under control.

I have no other active cancers or any treated within the last 3 years, except for minor skin cancers or superficial bladder cancer.

I have a history of seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive (R)-9bMS orally twice daily for up to 12 months, with dose escalation based on tolerance

12 months

Monthly visits (in-person) for dose adjustment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Quarterly visits (in-person) or medical record review

Data Analysis

Data collected during the trial is analyzed for safety and efficacy outcomes

12 months

What Are the Treatments Tested in This Trial?

Interventions

• (R)-9bMS

Trial Overview (R)-9bMS, an ACK1 inhibitor taken orally twice daily, is being tested in this Phase I trial to evaluate its safety and effectiveness against prostate cancer. The study will also determine the maximum tolerated dose and observe any potential anti-tumor responses over a period including treatment and follow-up.

How Is the Trial Designed?

Group I: Expansion: (R)-9bMS Experimental Treatment 1 Intervention

Patient will take (R)-9bMS twice daily by mouth for up to 6 months. Each cycle is 28 days. The assigned dose will be determined in the Dose Escalation portion of the trial.

Group II: Dose Escalation: (R)-9bMS Experimental Treatment 1 Intervention

Patient will take the assigned dose of (R)-9bMS twice daily by mouth for up to 6 months. Each cycle is 28 days.

Who Is Running the Clinical Trial?

TechnoGenesys, Inc.

Lead Sponsor

Trials

1

Recruited

30+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06705686

Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer To assess clinical outcomes and anti-tumor activity in patients treated with (R)-9bMS. ENDPOINTS: Primary Endpoint: Frequency of dose-limiting toxicities and ...

2. pcf.org pcf.org/wp-content/uploads/2019/09/Mahajan_Nupam.pdf

9bMS for treatment of Castration Resistant Prostate Cancer Conclusion: These data suggest that (R)-9bMS is effective at inhibiting proliferation and migration of. CRPCs in multiple mouse models of PC, including ...

3. synapse.patsnap.com synapse.patsnap.com/drug/a2beeb9f68974eb2a6732c64f420d17c

(R)-9b - Drug Targets, Indications, Patents (R)-9bMS, a small-molecule inhibitor of the non-receptor tyrosine kinase 2 (TNK2), significantly inhibited TNBC cell growth.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5512571/

ACK1 Regulates Histone H4 Tyr88-phosphorylation and ... (R)-9bMS attenuates AR and the splice variant-7 (AR-V7) transcription. To further interrogate whether the decrease in AR protein levels is a consequence of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0923753420360348

Epigenetic modulations and lineage plasticity in advanced ... Reversal of the pTry88-histone H4 epigenetic marks by the ACK1 inhibitor (R)-9bMS sensitizes naive and ADT-resistant prostate cancer cells and reduces AR ...

6. smartpatients.com smartpatients.com/trials/NCT06705686

Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer Treatment with (R)-9bMS suppressed Abi and Enz-resistant tumor growth in mice. Robust immune activation against prostate tumors was also reflected in mice ...

7. trial.medpath.com trial.medpath.com/clinical-trial/91a118e29064ea4b/nct06705686-first-in-human-trial-ack1-inhibitor-prostate-cancer

Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer Given the unique cancer suppressing properties of the (R)-9bMS compound, its safety and tolerability and proposed Phase 2 dosing will be evaluated in a first-in ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39293515/

Safety and clinical activity of BMS-986365 (CC-94676), a dual ... BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with mCRPC with potentially higher ...