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

NCT04662580 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ARX517-2011
• Study Type: interventional
• Target: 183
• Locations: 1 country
• Sites: 12

Brief Summary

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).

Conditions

Metastatic Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Area under the serum concentration-time curve (AUC) for ARX517 alone or in combination with ARPIs

  3 Year

• Maximum serum concentration (Cmax) for ARX517 alone or in combination with ARPIs

  3 Year

• Trough concentration (Ctrough) for ARX517 alone or in combination with ARPIs

  3 Year

• Incidence of ADA against ARX517 alone or in combination with ARPIs

  3 year

• Overall survival (OS)

  3 year

Other Outcomes (4)

• Evaluate of biomarkers

  3 years

• Evaluate PSMA expression

  3 years

• Assess changes in Brief Pain Inventory-Short Form (BPI-SF)

  3 year

Study Arms (3)

ARX517

EXPERIMENTAL

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+Apalutamide

EXPERIMENTAL

ARX517 and apalutamide

Drug: ARX517; Drug: Apalutamide

ARX517+AAP

EXPERIMENTAL

ARX517 and abiraterone acetate plus prednisone(AAP)

Drug: ARX517; Drug: Abiraterone acetate; Drug: Prednisone

Interventions

Abiraterone acetate DRUG

Oral tablet and will be given once daily by mouth.

ARX517+AAP

Prednisone 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.

ARX517+AAP

ARX517 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; ARX517+AAP; ARX517+Apalutamide

Apalutamide DRUG

Oral tablet and will be given once daily by mouth.

ARX517+Apalutamide

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male participants only
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• hour urine protein \> 1g/24h

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (12)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California, Los Angeles School of Medicine

Los Angeles, California, 90095-3000, United States

Location

UCSF Medical Center at Mission Bay

San Francisco, California, 94143-2350, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5116, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-5000, United States

Location

Washington University St. Louis School Medicine Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

GU Research Network

Omaha, Nebraska, 68130, United States

Location

Weill Cornell Medical College

New York, New York, 10021-5663, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

University of Washington

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• 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.

  PMID: 39172730 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 12, 2020
• First Posted: December 10, 2020
• Study Start: May 3, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 8, 2026

Record last verified: 2026-05

Locations

US (12)