ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer (ARX517)

A Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of ARX517 as Monotherapy and in Combination With Androgen Receptor Pathway Inhibitors in Subjects With Metastatic Prostate Cancer

This is a phase 1 study to assess the safety and tolerability of ARX517 as monotherapy or combination therapy in adult subjects with metastatic prostate cancer (mPC).

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Drug: ARX517; Drug: Apalutamide; Drug: Abiraterone acetate; Drug: Prednisone

Detailed Description

This is a first-in-human (FIH), Phase 1, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, PK, pharmacodynamic (PDy), and preliminary anti-tumor activity of ARX517 alone, or in combination with androgen receptor pathway inhibitors (ARPIs), in adult subjects with metastatic prostate cancer .

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90095-3000
      • University of California, Los Angeles School of Medicine
    • San Francisco, California, United States, 94143-2350
      • UCSF Medical Center at Mission Bay
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5116
      • Indiana University Melvin and Bren Simon Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5000
      • University of Michigan Comprehensive Cancer Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University St. Louis School Medicine Siteman Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • GU Research Network
  • New York
    • New York, New York, United States, 10021-5663
      • Weill Cornell Medical College
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Washington
    • Seattle, Washington, United States, 98101
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male and ≥18 years at the time of providing written informed consent.
• Histologically confirmed prostate adenocarcinoma.
• For subjects who have not undergone an orchiectomy, must be undergoing treatment with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist and must agree to continue such therapy while on study treatment. Subjects enrolled to mCRPC cohorts must have serum testosterone levels of ≤50ng/dL (1.73nM at Screening).
• Must receive prior treatment(s) as defined in the protocol for each cohort
• Documented evidence of disease progression on or after the most-recent prior regimen for mCRPC cohorts
• mCSPC combination cohorts: High volume metastatic disease documented by CT/MRI and/or 99mTC bone scan (for bone lesions)
• Adequate blood counts
• Must have at least 1 PSMA-positive metastatic lesion and no measurable PSMA-negative lesions by local assessment for alternative dosing regimen and combination cohorts.

Key Exclusion Criteria

• Receipt of chemotherapy within 21 days prior to enrollment; hormonal therapy (not including LHRH analogs) within 7 days prior to enrollment; palliative radiation therapy within 7 days prior to enrollment; or any other anticancer therapy within 21 days prior to enrollment or other therapy for monotherapy cohorts
• Receipt of more than 1 prior taxane regimen or non-taxane chemotherapy for prostate cancer for alternative dose regimen and mCRPC combination cohorts
• Receipt prior apalutamide, enzalutamide, or darolutamide, or AAP for mCRPC combination cohorts
• Receipt any prior chemotherapy or prior ARPI, and must be greater than 90 days of ADT prior to enrollment for mCSPC combination cohorts
• Use of chronic systemic glucocorticoids equivalent to > 10 mg prednisone daily. Note: short-term administration of systemic corticosteroids > 10 mg prednisone equivalent (e.g., for allergic reactions or management of immune- or infusion-related AEs) is allowed.
• Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, untreated CNS metastases are eligible provided they have been clinically stable (neurologically stable and not requiring steroids for at least 28 days prior to enrollment).
• History of any invasive malignancy (other than primary) within the previous 2 years prior to the enrollment date that requires active therapy or is at high risk of recurrence in the opinion of the investigator.
• Marked baseline prolongation of QT/QT interval corrected for heart rate (QTc), e.g., a triplicate-average QTc interval > 480 milliseconds (CTCAE Grade 2) using Fridericia's QT correction formula at any time within 28 days before enrollment, ongoing history of CTCAE Grade ≥2 QTc at enrollment, or anticipated need to perform repeat ECG evaluations to satisfy re-treatment criteria.
• Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease within 12 months prior to enrollment date.
• Clinically significant ocular findings by a qualified ophthalmologist or optometrist including active ocular infections or chronic corneal disorders unless approved by the Medical Monitor.
• Peripheral neuropathy Grade ≥ 2 within 28 days prior to enrollment.
• For combination cohorts with apalutamide: no prior history of seizure or condition that may predispose to seizure (including but not limited to prior cerebrovascular accident, TIA or loss of consciousness within the last 12 months, brain AVM, brain metastases).
• 24-hour urine protein > 1g/24h

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARX517; ARX517 will be administered via intravenous (IV) infusion, with the initial treatment regimen by weight-based infusion at an interval of every 3 weeks. Other treatment regimen may be explored.	Drug: ARX517; ARX517 is an ADC consisting of a humanized anti-PSMA monoclonal antibody (mAb) (IgG1κ) covalently conjugated to two (2) proprietary microtubule-disrupting toxins referred to as AS269.
Experimental: ARX517+Apalutamide; ARX517 and apalutamide	Drug: ARX517; ARX517 is an ADC consisting of a humanized anti-PSMA monoclonal antibody (mAb) (IgG1κ) covalently conjugated to two (2) proprietary microtubule-disrupting toxins referred to as AS269.; Drug: Apalutamide; Oral tablet and will be given once daily by mouth.
Experimental: ARX517+AAP; ARX517 and abiraterone acetate plus prednisone(AAP)	Drug: ARX517; ARX517 is an ADC consisting of a humanized anti-PSMA monoclonal antibody (mAb) (IgG1κ) covalently conjugated to two (2) proprietary microtubule-disrupting toxins referred to as AS269.; Drug: Abiraterone acetate; Oral tablet and will be given once daily by mouth.; Drug: Prednisone; Oral tablet and will be given once daily in metastatic castration-sensitive prostate cancer( mCSPC) and twice daily in metastatic castration-resistant prostate cancer (mCRPC) cohort by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess incidence of adverse events	Incidence and severity of adverse events or serious adverse events of ARX517 alone or in combination with ARPIs will be assessed to determine the safety and tolerability of the treatment using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5 (CTCAE).	1.5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival (OS) is defined as the time from first dose of study therapy to the date of death (any cause). Subjects who are alive will be censored at the last known time that the subject was alive.	3 year
Progression-free survival (PFS)	PFS is defined as the time between date of first dose of study therapy and date of progression or death, whichever occurs first, will be computed for response evaluable subjects. Subjects will be censored at time of subsequent therapy	3 year
Area under the serum concentration-time curve (AUC) for ARX517 alone or in combination with ARPIs	Pharmacokinetic parameter area under the serum concentration-time curve (AUC) will be analyzed through different analytes such as ADC, total antibody, and pAF-AS269	3 Year
Maximum serum concentration (Cmax) for ARX517 alone or in combination with ARPIs	Pharmacokinetic parameter maximum serum concentration (Cmax) will be analyzed through different analytes such as, ADC, total antibody, and pAF-AS269	3 Year
Trough concentration (Ctrough) for ARX517 alone or in combination with ARPIs	Pharmacokinetic parameter trough concentration (Ctrough) will be analyzed through different analytes such as, ADC, total antibody, and pAF-AS269	3 Year
Incidence of ADA against ARX517 alone or in combination with ARPIs	To assess the incidence of anti-drug antibodies (ADA) against ARX517 at selected timepoints	3 year
Assess changes in serum prostate specific antigen (PSA) levels	Proportion of subjects who show a confirmed reduction of 30%, 50%,and 90% from baseline in serum prostate specific antigen (PSA) levels (PSA30, PSA50, PSA 90)	3 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate of biomarkers	To evaluate exploratory blood based biomarkers related to study drug response	3 years
Evaluate PSMA expression	To evaluate relationship of PSMA expression and anti-tumor activity	3 years
Assess changes in Brief Pain Inventory-Short Form (BPI-SF)	A Brief Pain Inventory questionnaire will be utilized to assess subject quality of life. Higher scores mean a worse outcome	3 year
Assess changes in Functional Assessment of Cancer Therapy for Patients with Prostate Cancer (FACIT-P)	FACT-P questionnaire will be utilized to assess subject quality of life. Higher scores mean a worse outcome	3 year

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Collaborators: Johnson & Johnson
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Skidmore LK, Mills D, Kim JY, Knudsen NA, Nelson JD, Pal M, Wang J, Gc K, Gray MJ, Barkho W, Nagaraja Shastri P, Ramprasad MP, Tian F, O'Connor D, Buechler YJ, Zhang SS. Preclinical Characterization of ARX517, a Site-Specific Stable PSMA-Targeted Antibody-Drug Conjugate for the Treatment of Metastatic Castration-Resistant Prostate Cancer. Mol Cancer Ther. 2024 Dec 3;23(12):1842-1853. doi: 10.1158/1535-7163.MCT-23-0927.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 12, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Prostate Cancer; PSMA; ADC; Antibody drug conjugate; Metastatic castration-resistant prostate cancer; Prostate specific membrane antigen; PSMA ADC; Prostate neoplasia
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Androstenes; Androstanes; Abiraterone Acetate; Prednisone; apalutamide
• Other Study ID Numbers: ARX517-2011 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No