ARX517 in Subjects With Metastatic Castration-Resistant Prostate Cancer

Prostate Cancer Clinical Trial

— ARX517  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04662580
• Other study ID #: ARX517-2011(APEX-01)
• Status: Recruiting
• Phase: Phase 1
• Start date: July 27, 2021
• Est. completion date: March 2027

Study information

• Verified date: May 2024
• Source: Ambrx, Inc.
• Contact: Trial Inquiry
• Phone: 858.875.2400
• Email: ARX517-2011APEX-01Study[@]ambrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1 study to assess the safety and tolerability of ARX517 in adult subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 262
• Est. completion date: March 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.
• 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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• ARX517
ARX517 is an ADC consisting of a humanized anti-PSMA monoclonal antibody (mAb) (IgG1?) covalently conjugated to two (2) proprietary microtubule-disrupting toxins referred to as AS269.

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	The Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of California Los Angeles School of Medicine	Los Angeles	California
United States	Weill Cornell Medical College	New York	New York
United States	Urology Cancer Center, XCancer Research Network	Omaha	Nebraska
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UCSF	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Ambrx, Inc.	Johnson & Johnson

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluate of biomarkers	To evaluate exploratory blood based biomarkers related to study drug response	3 years
Other	Evaluate PSMA expression	To evaluate relationship of PSMA expression and anti-tumor activity	3 years
Other	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
Other	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
Primary	Assess incidence of adverse events	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).	1.5 Years
Secondary	Area under the serum concentration-time curve (AUC) for ARX517	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
Secondary	Maximum serum concentration (Cmax) for ARX517	Pharmacokinetic parameter maximum serum concentration (Cmax) will be analyzed through different analytes such as, ADC, total antibody, and pAF-AS269	3 Year
Secondary	Trough concentration (Ctrough) for ARX517	Pharmacokinetic parameter trough concentration (Ctrough) will be analyzed through different analytes such as, ADC, total antibody, and pAF-AS269	3 Year
Secondary	Incidence of ADA against ARX517	To assess the incidence of anti-drug antibodies (ADA) against ARX517 at selected timepoints	3 year
Secondary	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
Secondary	Assess changes in serum prostate specific antigen (PSA) levels	Proportion of subjects who show a confirmed reduction of 30% and 50% from baseline in serum prostate specific antigen (PSA) levels (PSA30, PSA50)	3 year
Secondary	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