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

NCT ID: NCT04662580

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

183 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-09

Study Completion Date

2028-12-29

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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 .

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Metastatic Prostate Cancer

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

ADC Antibody drug conjugate Prostate neoplasia Metastatic castration-resistant prostate cancer PSMA Prostate specific membrane antigen PSMA ADC Prostate Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

This study has dose-escalation (Phase 1a) and dose-expansion (Phase 1b) stages to identify the maximum tolerated dose (MTD) and/or recommended development doses (RDDs) of ARX517. The initial treatment regimen is by weight-based infusion at an interval of every 3 weeks. In the Phase 1b dose expansion stage, the Sponsor will evaluate cohorts with alternative dose regimens to determine RDD(s). The term "alternative dose regimen" refers to any monotherapy treatment regimen where ARX517 is not given at a fixed interval of every 3 weeks.

In the Phase 1b dose expansion stage, the Sponsor will also evaluate the safety and preliminary anti-tumor activity of ARX517 in combination with ARPIs (apalutamide or abiraterone acetate plus prednisone). ARPIs will be administered at the approved doses per product information. The starting dose of ARX517 to be given in combination with ARPIs will be determined by data emerging from the monotherapy dose expansion stage.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

ARX517

Intervention Type DRUG

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.

ARX517+Apalutamide

ARX517 and apalutamide

Group Type EXPERIMENTAL

ARX517

Intervention Type DRUG

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.

Apalutamide

Intervention Type DRUG

Oral tablet and will be given once daily by mouth.

ARX517+AAP

ARX517 and abiraterone acetate plus prednisone(AAP)

Group Type EXPERIMENTAL

ARX517

Intervention Type DRUG

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.

Abiraterone acetate

Intervention Type DRUG

Oral tablet and will be given once daily by mouth.

Prednisone

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Apalutamide

Oral tablet and will be given once daily by mouth.

Intervention Type DRUG

Abiraterone acetate

Oral tablet and will be given once daily by mouth.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status RECRUITING

University of California, Los Angeles School of Medicine

Los Angeles, California, United States

Site Status RECRUITING

UCSF Medical Center at Mission Bay

San Francisco, California, United States

Site Status RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Washington University St. Louis School Medicine Siteman Cancer Center

St Louis, Missouri, United States

Site Status RECRUITING

GU Research Network

Omaha, Nebraska, United States

Site Status COMPLETED

Weill Cornell Medical College

New York, New York, United States

Site Status RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status RECRUITING

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Study Contact

Role: CONTACT

Phone: 844-434-4210

Email: [email protected]

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 39172730 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ARX517-2011

Identifier Type: OTHER

Identifier Source: secondary_id

ARX517-2011

Identifier Type: -

Identifier Source: org_study_id