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Clinical Trials in the USA / NCT05067140
Active, not recruiting Phase 1/2

A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer

NCT05067140 · tracked via the Priya Life Science USA tracker
Sponsor
Novartis Pharmaceuticals
Phase
Phase 1/2
Started
2021-09-02
Last updated
2026-08-18

Condition(s) studied

Prostate Cancer Metastatic

Investigational drug(s) / intervention(s)

ARV-766AbirateroneCorticosteroid (e.g., prednisone/prednisolone)Androgen Deprivation Therapy (ADT)

ARV-766: Parts A and C: Daily oral dosages are determined by cohort review committee after initial starting dose cohort and each subsequent cohort completes 28 days of treatment. Part B: 100mg or 300mg oral tablet(s) once daily in 28 day cycles.

Abiraterone: Abiraterone is administered orally in combination with ARV-766, typically on an empty stomach with water, in accordance with prescribing information and standard clinical practice.

Corticosteroid (e.g., prednisone/prednisolone): Prednisone or prednisolone was administered in accordance with local prescribing information during treatment with abiraterone acetate.

Androgen Deprivation Therapy (ADT): Ongoing androgen deprivation therapy, including luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or prior orchiectomy, is maintained per investigator choice or patient preference.

Study summary

This first-in-human, Phase 1/2, open-label study evaluates the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of JSB462 (luxdegalutamide, previously ARV-766) administered as monotherapy and in combination with abiraterone in participants with metastatic prostate cancer. The study includes dose-escalation and cohort expansion components to determine the recommended Phase 2 dose and assess clinical activity.

Eligibility

Sex
MALE
Min age
18 Years
Max age
Healthy volunteers
No
Key Inclusion Criteria for Parts A, B, and C: * Participants must be able to take oral medication without crushing, dissolving, or chewing tablets * Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate * Progression on approved systemic therapies for metastatic prostate cancer (at least one must be a second-generation androgen inhibitor, e.g., abiraterone, enzalutamide, darolutamide, apalutamide) (Parts A and B only) * Progressive mCRPC (Parts A and B only) defined as: * Serum testosterone levels \<50 ng/dL (or ≤0.50 ng/mL or 1.73 nmol/L) using testosterone assays with a sensitivity of ≤30 ng/dL, within 28 days before study drug treatment * Radiographic evidence of metastatic disease (soft tissue disease per modified RECIST 1.1 criteria or bone disease per PCWG3) * Disease progression on or following the most recent systemic therapy * Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration) (Parts A and B only) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Metastatic castration resistant or sensitive prostate cancer with radiographic evidence of metastatic disease (soft tissue disease per modified RECIST 1.1 criteria or bone disease per PCWG3) (Part C) Key Exclusion Criteria for Parts A, B, and C: * Known symptomatic brain metastases requiring steroids (above physiologic replacement doses) * Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ or other low grade localized cancer. Eligibility for exception requires Sponsor approval * Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolic disease * Any of the following in the previous 6 months: congenital long QT syndrome, Torsade de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock (bifascicular block). Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade ≥2, atrial fibrillation of any grade (Grade ≥2 in the case of asymptomatic lone atrial fibrillation). Anticoagulation (heparin/lovenox only) can be allowed if indicated * QTcF \>480 msec at baseline based on ECG * Active inflammatory gastrointestinal disease, chronic diarrhea, diverticulitis, or previous gastric resection or lap band surgery * Participants taking sensitive BCRP and P-glycoprotein (P-gp) substrates or substrates with narrow therapeutic indices, strong CYP3A4 inhibitors and inducers, restricted medications described in the study protocol and the Investigator's Brochure, and additionally for Part C, CYP2D6 substrates with a narrow therapeutic index * Inadequate bone marrow function defined as follows (with no transfusion of blood products or use of hematopoietic growth factors in the 28 days prior to start of therapy): * Absolute neutrophil count \<1,500/mm3 or \<1.5 × 109/L * Platelets \<100,000/mm3 or \<100 × 109/L * Hemoglobin \<9 g/dL * Inadequate renal function defined as estimated creatinine clearance (Clcr) ≤60 mL/min using Cockcroft-Gault formula or eGFR ≤60 mL/min/1.73m3 using the CKD-EPI equation * Electrolyte imbalances of clinically significant hypokalemia, hypomagnesemia, and/or hypocalcemia (Part C only) * Inadequate liver function defined as: * Total serum bilirubin \>1.5× upper limit of normal (ULN) unless the participant has documented Gilbert syndrome * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of \>2.5× ULN if there is NO liver involvement secondary to tumor OR \>5.0× ULN if there is liver involvement secondary to tumor * Prior treatment with a second-generation NHA such as abiraterone, enzalutamide, darolutamide, or apalutamide (Part C only). Note: prior chemotherapy is allowed. Other inclusion/exclusion criteria may apply.

Primary outcome measure(s)

Trial sites (17)

FacilityCityRegionStatus
City of Hope National Medical Duarte California
University of California San Diego - Moores Cancer Center La Jolla California
Providence Saint Johns Health Ctr Santa Monica California
Yale Cancer Center New Haven Connecticut
Florida Cancer Specialists Fort Myers Florida
Chesapeake Urology Associates Baltimore Maryland
Massachusetts General Hospital Boston Massachusetts
Karmanos Cancer Institute Detroit Michigan
Roswell Park Cancer Institute Buffalo New York
Fox Chase Cancer Center Philadelphia Pennsylvania
Univ of Pittsburgh Cancer Inst Pittsburgh Pennsylvania
Carolina Urologic Research Center Myrtle Beach South Carolina
SCRI Oncology Partners Nashville Tennessee
Urology San Antonio San Antonio Texas
University of Virginia Medical Center Charlottesville Virginia
Virginia Cancer Specialists Fairfax Virginia
University of Wisconsin Paul P Carbone Comp Cancer Center Madison Wisconsin

On this site

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05067140 on ClinicalTrials.gov ↗ ← All trials in the USA