Metastatic Prostate CancerPhase 1ARX517NCT04662580
ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer
A Phase 1 study testing ARX517, Apalutamide and Abiraterone acetate in people with Metastatic Prostate Cancer, run by Janssen Research & Development, LLC at 12 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Prostate Cancer
- What is being tested?
- ARX517, Apalutamide and Abiraterone acetate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 183 participants
- Where
- 12 sitesUnited States
- Study dates
- 3 May 2021to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 13Show fewer
- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-5000
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202-5116
UC San Diego Moores Cancer Center
La Jolla, California, 92093
University of California, Los Angeles School of Medicine
Los Angeles, California, 90095-3000
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Weill Cornell Medical College
New York, New York, 10021-5663
GU Research Network
Omaha, Nebraska, 68130
UCSF Medical Center at Mission Bay
San Francisco, California, 94143-2350
University of Washington
Seattle, Washington, 98101
Washington University St. Louis School Medicine Siteman Cancer Center
St Louis, Missouri, 63110
About this study
Official title: 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).
Read the 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 .
- Conditions
- Metastatic Prostate Cancer
- Being tested
- ARX517, Apalutamide, Abiraterone acetate, Prednisone
- Keywords
- ADC, Antibody drug conjugate, Prostate neoplasia, Metastatic castration-resistant prostate cancer, PSMA, Prostate specific membrane antigen, PSMA ADC, Prostate Cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARX517Drug
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.
ApalutamideDrug
Oral tablet and will be given once daily by mouth.
Abiraterone acetateDrug
Oral tablet and will be given once daily by mouth.
PrednisoneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: ARX517 |
| ARX517+Apalutamide | Experimental | ARX517 and apalutamide Receives: Drug: ARX517; Drug: Apalutamide |
| ARX517+AAP | Experimental | ARX517 and abiraterone acetate plus prednisone(AAP) Receives: Drug: ARX517; Drug: Abiraterone acetate; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 1.5 Years
Secondary outcomes (7)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 3 year
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.
Measured: 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)
Measured: 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
Measured: 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2020
- Study start3 May 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Prostate CancerStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04662580
- Sponsor's protocol ID
- ARX517-2011
- Other IDs
- ARX517-2011
- Acronym
- ARX517
- Status last verified
- Nov 2026
- First submitted
- 12 Sep 2020
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 39172730
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04662580
- Acronym / sponsor ID
- ARX517 / ARX517-2011
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 183 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 3 May 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 10 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| ARX517 | Experimental | Drug: ARX517ARX517 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. |
| ARX517+Apalutamide | Experimental | Drug: ARX517, Drug: ApalutamideARX517 and apalutamide |
| ARX517+AAP | Experimental | Drug: ARX517, Drug: Abiraterone acetate, Drug: PrednisoneARX517 and abiraterone acetate plus prednisone(AAP) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARX517ARX517 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 | ARX517, ARX517+AAP, ARX517+Apalutamide |
| ApalutamideOral tablet and will be given once daily by mouth. | Drug | ARX517+Apalutamide |
| Abiraterone acetateOral tablet and will be given once daily by mouth. | Drug | ARX517+AAP |
| PrednisoneOral 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. | Drug | ARX517+AAP |
Primary outcome
Assess incidence of adverse events
Time frame: 1.5 Years
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).
7 secondary outcomes
Area under the serum concentration-time curve (AUC) for ARX517 alone or in combination with ARPIs
Time frame: 3 Year
Maximum serum concentration (Cmax) for ARX517 alone or in combination with ARPIs
Time frame: 3 Year
Trough concentration (Ctrough) for ARX517 alone or in combination with ARPIs
Time frame: 3 Year
Incidence of ADA against ARX517 alone or in combination with ARPIs
Time frame: 3 year
Overall survival (OS)
Time frame: 3 year
Assess changes in serum prostate specific antigen (PSA) levels
Time frame: 3 year
Progression-free survival (PFS)
Time frame: 3 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Derived from this study: PubMed 39172730Skidmore 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ARX517, Apalutamide and Abiraterone acetate in people with Metastatic Prostate Cancer, run by Janssen Research & Development, LLC at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess incidence of adverse events (time frame: 1.5 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04662580, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.