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ARX517 in Subjects With Advanced Solid Tumor (ARX517)

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ClinicalTrials.gov Identifier: NCT04662580
Recruitment Status : Recruiting
First Posted : December 10, 2020
Last Update Posted : August 27, 2021
Sponsor:
Information provided by (Responsible Party):
Ambrx, Inc.

Tracking Information
First Submitted Date  ICMJE September 12, 2020
First Posted Date  ICMJE December 10, 2020
Last Update Posted Date August 27, 2021
Actual Study Start Date  ICMJE April 27, 2021
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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
Original Secondary Outcome Measures  ICMJE Same as current
Current 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE ARX517 in Subjects With Advanced Solid Tumor
Official Title  ICMJE 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 Advanced Tumors Who Failed Prior Standard Therapies
Brief Summary 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 Advanced Solid Tumor with known PSMA Who Failed Prior Standard Therapies
Detailed Description This is a first-in-human, Phase 1, multicenter, open-label, single arm, dose escalation, and dose expansion study to evaluate the safety, PK, and preliminary anti-tumor activity of ARX517 in adult subjects with advanced solid tumor who failed prior standard therapies. The study includes 2 parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2). In Part 1, the subject will be enrolled with a starting dose of 0.32 mg/kg, and the study will evaluate up to 6 dose levels of ARX517 (0.32 mg/kg, 0.64 mg/kg, 1.07 mg/kg, 1.4 mg/kg, 1.7 mg/kg, and 2.0 mg/kg) by intravenous infusion once every 3 weeks (Q3W). If the planned highest dose level of 2.0 mg/kg is well tolerated, a higher dose level of ARX517 may be evaluated based on the SMC recommendation. Similarly, doses lower than the pre-specified lowest dose of 0.32 mg/kg and additional intermediate dose levels of ARX517 may also be considered if needed. Decisions about enrollment suspension, resumption, and study termination will be made by the Sponsor based on recommendations from SMC. DLT will be evaluated in the first cycle of 21 days for Q3W. MTD and /or putative recommended phase II dose (RP2D) will be selected based on all available safety, tolerability, PK, and primary anti-tumor activity data. To ensure that the selected RP2D is not associated with an increased risk of serious adverse events, multiple "putative RP2D" doses may be selected for further evaluation based on SMC recommendation. The number of subjects to be enrolled in the dose-expansion part will be based on the number of doses selected for expansion and the results of the dose escalation part. Part 2 will not exceed 40 subjects.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
This is a first-in-human, Phase 1, multicenter, open-label, single arm, dose escalation, and dose expansion study to evaluate safety, PK, and preliminary anti-tumor activity of ARX517 in adult subjects with advanced solid tumor. The study includes 2 parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2). In Part 1, the study will evaluate up to 6 dose levels (0.32 mg/kg, 0.64 mg/kg, 1.07 mg/kg, 1.4 mg/kg, 1.7 mg/kg, and 2.0 mg/kg) once every 3 weeks (Q3W). If the planned highest dose level 2.0 mg/kg is well tolerated, a higher dose levels of ARX517 may be evaluated. Similarly, doses lower than the pre-specified lowest dose of 0.32 mg/kg and additional intermediate dose levels of ARX517 may also be considered if needed. To ensure that the selected RP2D is appropriate, multiple "putative RP2D" doses may be selected for further evaluation. The number of subjects to be enrolled in Part 2 will not exceed 40 subjects.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumor
  • Solid Neoplasm
Intervention  ICMJE 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  ICMJE
  • Experimental: ARX517 Part 1 (Dose Escalation)
    Subjects will be administered ascending dose levels of ARX517 via intravenous (IV) infusion every 3 weeks. Subjects will be enrolled into escalating dose levels during the Dose Escalation period of the study.
    Intervention: Drug: ARX517
  • Experimental: ARX517 Part 2 (Dose Expansion)
    Subjects will be administered maximum dose levels of ARX517 via intravenous (IV) infusion every 3 weeks. Subjects will receive the maximum tolerated dose during the Dose Expansion period of the study.
    Intervention: Drug: ARX517
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 8, 2020)
76
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2024
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male subjects ≥18 years at the time of providing written informed consent
  2. Pathologically confirmed adenocarcinoma of the prostate or other solid tumors
  3. For prostate cancer, ongoing therapy with a gonadotropin-releasing hormone agonist or antagonist AND serum testosterone level <50 ng/dL at Screening
  4. For prostate cancer, prior treatment with at least 2 Food and Drug Administration (FDA) approved treatments for metastatic castration-resistant prostate cancer.
  5. Metastatic disease documented by computed tomography (CT)/ magnetic resonance imaging (MRI) and/ or bone scan; images obtained within 28 days prior to the start of study medication will be accepted as baseline
  6. For prostate cancer, meet the criteria of disease progression according to the recommendations of the Prostate Cancer Working Group (PCWG) 3 by one of the following criteria:

    1. A sequential rise of PSA (second value obtained at a minimum of 1 week later) from a baseline measurement of at least 2 ng/mL (1 ng/mL is the minimum starting value if confirmed rise is only indication of progression)
    2. Radiographic progression (CT/MRI) by Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) criteria
    3. Nuclear scan progression by new lesions
  7. For prostate cancer, discontinuation of flutamide or nilutamide, and other non steroidal anti-androgens at least 4 weeks prior to the start of study drug; discontinuation of bicalutamide at least 6 weeks prior to start of study drug.
  8. Discontinuation of radiotherapy >4 weeks prior
  9. Eastern Cooperative Oncology Group performance status of 0 to 1 at Screening
  10. Adequate organ function with following blood counts at Screening:
  11. Adequate organ function with following Chemistry values at Screening:
  12. Life expectancy of at least 6 months at Screening as per Investigator's judgment
  13. Willing and able to provide written informed consent for participation in the study, and comply with all protocol requirements and assessments
  14. Agrees to use contraception during the Treatment Period plus an additional 120 days after the last dose of study treatment and must refrain from donating sperm during this period.

Exclusion Criteria:

  1. History of allergic reactions to any component of the ARX517.
  2. Impaired pituitary or adrenal gland function (e.g., Addison's disease, Cushing's syndrome)
  3. Initiation of bisphosphonate or denosumab therapy within 30 days prior to the start of study medication; subjects who are on a stable dose of these medications for at least 30 days at the time of starting study drug are eligible
  4. Therapy with estrogen within 30 days prior to the start of study drug
  5. Use of systemic glucocorticoids equivalent to >10 mg prednisone daily; subjects who have discontinued or are on reduced daily dose are eligible within 14 days prior to the start of study drug
  6. Use of any medication such as finasteride/dutasteride known to decrease PSA levels (e.g., saw palmetto) within 30 days of start of study drug
  7. Have central nervous system (CNS) metastasis, unless the CNS metastasis was treated with local therapy and has proven to be stable over the last 2 months prior to Screening, and not currently requiring ongoing systemic steroid treatment
  8. History of other malignancy within the previous 2 years (no longer being actively treated), except basal cell carcinoma
  9. Marked baseline prolongation of QT/QTc interval, e.g. repeated demonstrated of a QTc interval > 480 milliseconds (ms) (CTCAE grade 1) using Fridericia's QT correction formula. Major surgery within 30 days prior to the start of study drug
  10. Blood transfusion within 30 days of Screening
  11. Serious and /or persistent infection within 14 days of the start of study drug
  12. Treatment with any investigational drug within 4 weeks prior to Day 1 of the study
  13. Known seropositive test for human immunodeficiency virus or seropositive test for hepatitis C virus or hepatitis B virus (testing for hepatitis C and hepatitis B is not required)
  14. Prior history of clinically significant lung disease, pneumonitis, or other clinically significant lung disease within 12 months prior to Screening, with the exception of that directly attributable to the presence of lung metastases from their underlying cancer.
  15. Prior history of clinically significant ocular events, or any current ongoing active ocular infections.
  16. Major surgery within 30 days prior to the start of the study drug. Poorly controlled diabetes, hypertension, history of class III or IV heart failure.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Inquiry 858.875.2400 ARX517-2011APEX-01Study@ambrx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04662580
Other Study ID Numbers  ICMJE ARX517-2011
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  ICMJE Not Provided
Responsible Party Ambrx, Inc.
Study Sponsor  ICMJE Ambrx, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ambrx Ambrx, Inc.
PRS Account Ambrx, Inc.
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP