(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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

TITLE: Phase 1 First in Human Trial to Assess Safety and Tolerability of the Novel ACK1 Inhibitor (R)-9bMS in Patients with Prostate Cancer (PHAROS) STUDY DESCRIPTION: Prostate cancer (PC) patients receive androgen deprivation therapy (ADT), but recalcitrant disease recurs typically within 2-3 years, referred to as the Castration Resistant Prostate Cancer (CRPC). Androgen receptor (AR) targeted therapies, such as Enzalutamide (Enz) or Abiraterone (Abi), are FDA-approved therapeutics for CRPC patients. However, virtually all patients develop resistance. A non-receptor tyrosine kinase, ACK1 act as a novel epigenetic modifier in prostate tumors, regulating AR and its splice variant, AR-V7 expression. A new class of ACK1 small molecule inhibitor, (R)-9bMS, was developed that exhibited excellent drug-like properties. Treatment with (R)-9bMS suppressed Abi and Enz-resistant tumor growth in mice. Robust immune activation against prostate tumors was also reflected in mice treated with ACK1 inhibitor, (R)-9bMS. Importantly (R)-9bMS functionally reinvigorated peripheral blood mononuclear cells (PBMCs) of CRPC patients to mount a robust immune response against CRPC organoids. Collectively, these data indicate that the ACK1 inhibitor, (R)-9bMS, fulfills a unique niche, wherein it not only suppressed AR/AR-V7 within the tumor milieu, but also activated host immune system by overcoming CSK-restrained LCK activity, to mount a robust 'dual' anti-tumor response. OBJECTIVES: Primary Objective: To assess the safety and tolerability of (R)-9bMS in patients with metastatic castration-resistant prostate cancer. Secondary Objectives: To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of (R)-9bMS in patients with CRPC. To determine the pharmacokinetics (PK) of (R)-9bMS in patients after single and multiple dose oral administration. To assess clinical outcomes and anti-tumor activity in patients treated with (R)-9bMS. ENDPOINTS: Primary Endpoint: Frequency of dose-limiting toxicities and toxicity and severe AEs per CTCAE v 5.0. Secondary Endpoints: * RP2D (recommended phase 2 dose) * PK (pharmacokinetics) * PSA responses * Duration of responses * ORR (objective response rate) * OS (overall survival) * PFS (progression free survival) * DSS (disease specific survival) * Toxicity and severe AEs per CTCAE v 5.0 STUDY POPULATION: Approximately 18-30 adult patients with a histologic or cytologic diagnosis of metastatic castration resistant prostate cancer will be enrolled. PHASE: Phase I DESCRIPTION OF SITES: This study will be open to enrollment at the University of Wisconsin Carbone Cancer Center DESCRIPTION OF STUDY INERVENTION: (R)-9bMS will be taken by mouth twice daily until completion of 12 cycles, progression or intolerance STUDY DURATION: 12 months for enrollment + 12 months treatment + 12 months follow-up + 12 months for data analysis = 48 months.

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.

Research Team

Douglas McNeel, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

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

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

I have a history of seizures.

Timeline

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

Treatment Details

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.

Participant Groups

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+