ARX517 in Subjects With Metastatic Castration-Resistant Prostate Cancer (ARX517)

• ClinicalTrials.gov Identifier: NCT04662580
• Recruitment Status: Recruiting
• First Posted: December 10, 2020
• Last Update Posted: May 10, 2024
• Sponsor: Ambrx, Inc.
• Collaborator: Johnson & Johnson
• Information provided by (Responsible Party): Ambrx, Inc.

Tracking Information

• First Submitted Date: September 12, 2020
• First Posted Date: December 10, 2020
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: July 27, 2021
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 8, 2024)

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).

Original Primary Outcome Measures (submitted: December 8, 2020)

• The primary objectives of Part 1: Safety and tolerability of ARX517 [ Time Frame: 1.5 Years ]
  The primary objectives of Part 1 are: • To assess and establish the safety and tolerability of ARX517
• The primary objectives of Part 1: [ Time Frame: 1.5 years ]
  To determine the maximum tolerated dose (MTD) and/or establish a recommended phase 2 dose (RP2D).
• The primary objective of Part 2 is: To further assess the safety and tolerability of ARX517 including multi cycle safety [ Time Frame: 1.5 years ]
  To assess the safety and tolerability of ARX517 further including multi cycle safety at PR2D

Current Secondary Outcome Measures (submitted: May 8, 2024)

• 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

Original Secondary Outcome Measures (submitted: December 8, 2020)

• PK profile of ARX517-ADC [ Time Frame: 3 Year ]
  The secondary objectives of Part 1 and part 2 are: • To assess the pharmacokinetic (PK) profile of ARX517 antibody drug conjugates (ADC),
• PK profile of ARX517-total antibody [ Time Frame: 3 year ]
  To assess the pharmacokinetic (PK) profile of ARX517 total antibody
• PK profile of ARX517-pAF-AS269 [ Time Frame: 3 years ]
  To assess the pharmacokinetic (PK) profile of ARX517 free payload pAF-AS269
• To assess the presence of antidrug antibodies (ADA) [ Time Frame: 3 year ]
  To assess the presence of anti-drug antibodies (ADA), from baseline, during the treatment and follow up

Current Other Pre-specified Outcome Measures (submitted: May 8, 2024)

• 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

Original Other Pre-specified Outcome Measures (submitted: December 8, 2020)

• Evaluate of surrogate biomarkers-CTC [ Time Frame: 3 years ]
  To assess the preliminary evidence of clinical activity by serial evaluations of surrogate biomarkers such as CTC
• Evaluate of surrogate biomarkers-PSA [ Time Frame: 3 years ]
  To assess the preliminary evidence of clinical activity by serial evaluations of surrogate biomarkers such as PSA, and imaging
• Evaluate of surrogate biomarkers- imaging [ Time Frame: 3 year ]
  To assess the preliminary evidence of clinical activity by serial evaluations of surrogate biomarkers such as imaging

Descriptive Information

• Brief Title: ARX517 in Subjects With Metastatic Castration-Resistant Prostate Cancer
• 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
• Brief 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).
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

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

• Condition: Prostate Cancer

Intervention

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.

Study Arms

Experimental: ARX517

ARX517 will be administered via intravenous (IV) infusion every 3, or 4 weeks.

Intervention: Drug: ARX517

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 8, 2024): 262
• Original Estimated Enrollment (submitted: December 8, 2020): 76
• Estimated Study Completion Date: March 2027
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Male participants only

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Inquiry; 858.875.2400; ARX517-2011APEX-01Study@ambrx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04662580
• Other Study ID Numbers: ARX517-2011(APEX-01)
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ambrx, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ambrx, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Johnson & Johnson

Investigators

• Study Director: Ambrx; Ambrx, Inc.

• PRS Account: Ambrx, Inc.
• Verification Date: May 2024