ARX517 in Subjects With Metastatic Castration-Resistant Prostate Cancer (ARX517)
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ClinicalTrials.gov Identifier: NCT04662580 |
Recruitment Status :
Recruiting
First Posted : December 10, 2020
Last Update Posted : May 10, 2024
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Condition or disease | Intervention/treatment | Phase |
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Prostate Cancer | Drug: ARX517 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 262 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | This is a first-in-human, Phase 1, multicenter, open-label study to evaluate the safety, PK, PDy, and preliminary anti-tumor activity of ARX517 in adult subjects with mCRPC with serum testosterone level < 50 ng/dL at screening who are resistant or refractory to standard therapies. Phase 1a (dose-escalation) and Phase 1b (dose-expansion) stages will identify the MTD and/or RDDs. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 in Subjects With Metastatic Castration-Resistant Prostate Cancer Who Are Resistant or Refractory to Prior Standard Therapies |
Actual Study Start Date : | July 27, 2021 |
Estimated Primary Completion Date : | December 2025 |
Estimated Study Completion Date : | March 2027 |
Arm | Intervention/treatment |
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Experimental: ARX517
ARX517 will be administered via intravenous (IV) infusion every 3, or 4 weeks.
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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. |
- Assess incidence of adverse events [ Time Frame: 1.5 Years ]Incidence and severity of adverse events or serious adverse events of ARX517 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).
- Area under the serum concentration-time curve (AUC) for ARX517 [ Time Frame: 3 Year ]Pharmacokinetic parameter area under the serum concentration-time curve (AUC) will be analyzed through different analytes such as ADC, total antibody, and pAF-AS269
- Maximum serum concentration (Cmax) for ARX517 [ Time Frame: 3 Year ]Pharmacokinetic parameter maximum serum concentration (Cmax) will be analyzed through different analytes such as, ADC, total antibody, and pAF-AS269
- Trough concentration (Ctrough) for ARX517 [ Time Frame: 3 Year ]Pharmacokinetic parameter trough concentration (Ctrough) will be analyzed through different analytes such as, ADC, total antibody, and pAF-AS269
- Incidence of ADA against ARX517 [ Time Frame: 3 year ]To assess the incidence of anti-drug antibodies (ADA) against ARX517 at selected timepoints
- Overall survival (OS) [ Time Frame: 3 year ]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.
- Assess changes in serum prostate specific antigen (PSA) levels [ Time Frame: 3 year ]Proportion of subjects who show a confirmed reduction of 30% and 50% from baseline in serum prostate specific antigen (PSA) levels (PSA30, PSA50)
- Progression-free survival (PFS) [ Time Frame: 3 year ]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
- Evaluate of biomarkers [ Time Frame: 3 years ]To evaluate exploratory blood based biomarkers related to study drug response
- Evaluate PSMA expression [ Time Frame: 3 years ]To evaluate relationship of PSMA expression and anti-tumor activity
- Assess changes in Brief Pain Inventory-Short Form (BPI-SF) [ Time Frame: 3 year ]A Brief Pain Inventory questionnaire will be utilized to assess subject quality of life. Higher scores mean a worse outcome
- Assess changes in Functional Assessment of Cancer Therapy for Patients with Prostate Cancer (FACIT-P) [ Time Frame: 3 year ]FACT-P questionnaire will be utilized to assess subject quality of life. Higher scores mean a worse outcome
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Gender Based Eligibility: | Yes |
Gender Eligibility Description: | Male participants only |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Male subjects ≥ 18 years at the first time of providing written informed consent.
- Histologically confirmed prostate adenocarcinoma.
- Documented metastatic disease and evidence of disease progression
- Castration-resistant prostate cancer defined as surgical or medical castration with serum testosterone levels of ≤ 50 ng/dL (1.73 nM) at Screening. For patients 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.
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Prior receipt of the following for metastatic prostate cancer:
- at least two lines of treatment
- at least two Food and Drug Administration (FDA)-approved therapies with at least one being a second-generation androgen receptor signaling inhibitor (e.g., abiraterone, darolutamide, apalutamide, or enzalutamide).
- Adequate blood counts
Key Exclusion Criteria:
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04662580
Contact: Trial Inquiry | 858.875.2400 | ARX517-2011APEX-01Study@ambrx.com |
United States, California | |
University of California Los Angeles School of Medicine | Recruiting |
Los Angeles, California, United States, 90095 | |
UCSF | Recruiting |
San Francisco, California, United States, 94143 | |
United States, Georgia | |
The Winship Cancer Institute of Emory University | Recruiting |
Atlanta, Georgia, United States, 30322 | |
United States, Indiana | |
Indiana University Melvin and Bren Simon Cancer Center | Recruiting |
Indianapolis, Indiana, United States, 46202 | |
United States, Michigan | |
University of Michigan Comprehensive Cancer Center | Recruiting |
Ann Arbor, Michigan, United States, 48109 | |
United States, Missouri | |
Washington University School of Medicine | Recruiting |
Saint Louis, Missouri, United States, 63110 | |
United States, Nebraska | |
Urology Cancer Center, XCancer Research Network | Recruiting |
Omaha, Nebraska, United States, 68130 | |
United States, New York | |
Weill Cornell Medical College | Recruiting |
New York, New York, United States, 10065 | |
United States, Washington | |
University of Washington | Recruiting |
Seattle, Washington, United States, 98195 |
Study Director: | Ambrx | Ambrx, Inc. |
Responsible Party: | Ambrx, Inc. |
ClinicalTrials.gov Identifier: | NCT04662580 |
Other Study ID Numbers: |
ARX517-2011(APEX-01) |
First Posted: | December 10, 2020 Key Record Dates |
Last Update Posted: | May 10, 2024 |
Last Verified: | May 2024 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
ADC Antibody drug conjugate Prostate neoplasma Castration-resistant PSA increased |
PSMA Prostate specific membrane antigen PSMA ADC Prostate Cancer |
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms |
Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases |