Actively Recruiting
Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer
Led by TechnoGenesys, Inc. · Updated on 2026-03-20
40
Participants Needed
1
Research Sites
106 weeks
Total Duration
On this page
Sponsors
T
TechnoGenesys, Inc.
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed metastatic castration-resistant prostate cancer (mCRPC).
- Evidence of metastatic disease on imaging; any metastasis type or location allowed.
- Currently receiving androgen deprivation therapy or have had surgical castration.
- Castrate testosterone level of 50 ng/dL or less maintained throughout study.
- Evidence of progressive castration-resistant prostate cancer with rising PSA or radiographic progression.
- Prior progression on at least one novel hormonal agent (e.g., enzalutamide, abiraterone).
- Prior palliative radiation for bone metastasis completed at least 14 days before enrollment; other radiation completed at least 28 days prior.
- Recovery to baseline or grade 1 or less from prior treatment toxicities unless stable on supportive therapy.
- Age 18 years or older.
- ECOG performance status of 0 or 1.
- Normal bone marrow and organ function as specified (including blood counts, liver and kidney tests).
- Corrected QT interval (QTcF) of 500 ms or less.
- Ability to understand and sign informed consent.
- Willingness and ability to undergo biopsy if in MTD cohort.
- Use of two forms of contraception including one barrier method if sexually active with female partners during and for 5 months after study treatment.
You will not qualify if you...
- Use of any small molecule kinase inhibitor within 14 days before first dose.
- Small cell or non-adenocarcinoma prostate cancer histology.
- Inability to swallow pills.
- Use of systemic corticosteroids >10 mg prednisone equivalent or immunosuppressive meds within 14 days before treatment (except certain allowed steroids).
- Active malignancy other than prostate cancer requiring treatment within 3 years.
- Receiving other investigational agents.
- Use of anti-androgen receptor agents or abiraterone within 14 days or 5 half-lives before treatment.
- Use of Radium-223 or radioligands within 28 days before treatment.
- Gastrointestinal conditions affecting drug absorption.
- Blood transfusion within 28 days before screening.
- Use of hormonal supplements with anti-tumor activity within 28 days before treatment.
- Initiation of bone-modifying agents after study drug start not allowed.
- Known brain metastases unless treated and stable for at least 4 weeks.
- History of seizures.
- Allergic reactions to similar compounds.
- Uncontrolled significant illness including serious heart conditions, uncontrolled hypertension, recent stroke or thromboembolism.
- Gastrointestinal disorders with risk of perforation or fistula.
- Significant bleeding history within 12 weeks.
- Pulmonary lesions invading vessels.
- Other clinically significant disorders precluding safe participation.
- Active hepatitis B, C, or active HIV unless well controlled.
- History of organ transplant.
- Major surgery within 8 weeks before treatment start.
- Conditions compromising safety or study adherence.
- Psychiatric or substance abuse disorders interfering with participation.
- Concurrent enrollment in other treatment investigational studies (except long-term follow-up).
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Trial Site Locations
Total: 1 location
1
University of Wisconsin Carbone Cancer Center (UWCCC) - Cancer Connect
Madison, Wisconsin, United States, 53792
Actively Recruiting
Research Team
N
Nupam Mahajan, PhD
CONTACT
G
Gerald Andriole, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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