OncoMatch/Clinical Trials/NCT06705686
Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer
Is NCT06705686 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies (R)-9bMS for metastatic castration-resistant prostate cancer (crpc).
Treatment: (R)-9bMS — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Prostate Cancer
Disease stage
Metastatic disease required
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Must have received: novel hormonal agent (enzalutamide, abiraterone, apalutamide, darolutamide) — castration-sensitive or castration-resistant
Patients must have had prior disease progression on at least one novel hormonal agent (NHA) (eg enzalutamide, abiraterone, apalutamide, darolutamide, etc.); treatment with NHA could have occurred in the castration-sensitive or castration-resistant setting.
Cannot have received: small molecule kinase inhibitor
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before first dose of study treatment.
Cannot have received: anti-androgen receptor agent
Exception: within 14 days or 5 half-lives, whichever is longer, prior to the start of study drug
Any anti-androgen receptor agents or abiraterone (or similar CYP17,20 lyase inhibitor) within 14 days or 5 half-lives, whichever is longer, prior to the start of study drug.
Cannot have received: radioligand/radiopharmaceutical (Radium-223)
Exception: within 28 days prior to the start of study drug
Use of Radium-223 or other radioligand/radiopharmaceutical within 28 days prior to the start of study drug
Cannot have received: hormonal agent or supplement with potential anti-tumor activity against prostate cancer
Exception: within 28 days prior to the start of study drug
Use of hormonal agents or supplements with potential anti-tumor activity against prostate cancer, as determined by the PI, within 28 days prior to the start of study drug.
Lab requirements
Blood counts
Absolute neutrophil count ≥ 1,500/mm3 without granulocyte colony-stimulating factor support; White blood cell count ≥ 2,000/mm3; Platelets ≥ 100,000/mm3 without transfusion; Hemoglobin ≥ 9.0 g/DL
Kidney function
Serum creatinine ≤ 1.5 x IULN or calculated creatinine clearance ≥ 45 mL/min by Cockcroft-Gault; Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) (only evaluated if creatinine abnormal per criteria above)
Liver function
Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3.0 x IULN); AST(SGOT), ALT(SGPT) ≤ 3.0 x IULN; Moderate to severe hepatic impairment (Child-Pugh B or C) excluded
Cardiac function
Corrected QT interval calculated by the Fridericia formula (QTcF) ≤ 500 ms (by ECG); PT/INR or PTT < 1.5 x IULN (unless participant is receiving anticoagulant therapy and these are within intended therapeutic ranges for anticoagulant)
Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,500/mm3 without granulocyte colony-stimulating factor support * White blood cell count ≥ 2,000/mm3 * Platelets ≥ 100,000/mm3 without transfusion * Hemoglobin ≥ 9.0 g/DL * Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3.0 x IULN) * AST(SGOT), ALT(SGPT) ≤ 3.0 x IULN * Serum creatinine ≤ 1.5 x IULN or calculated creatinine clearance ≥ 45 mL/min by Cockcroft-Gault * Serum albumin ≥ 2.8 g/dL * Urine protein/creatinine ration (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) (only evaluated if creatinine abnormal per criteria above * PT/INR or PTT < 1.5 x IULN (PT/INR must be drawn < 7 days prior to biopsy for those patients treated in MTD cohort), unless participant is receiving anticoagulant therapy and these are within intended therapeutic ranges for anticoagulant. Corrected QT interval calculated by the Fridericia formula (QTcF) ≤ 500 ms (by ECG).
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- University of Wisconsin Carbone Cancer Center (UWCCC) - Cancer Connect · Madison, Wisconsin
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