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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.

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

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Solid Neoplasm Drug: ARX517 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
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
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 Advanced Tumors Who Failed Prior Standard Therapies
Actual Study Start Date : April 27, 2021
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : August 2024

Arm Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  1. 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


  2. 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).

  3. 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


Secondary Outcome Measures :
  1. 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),


  2. PK profile of ARX517-total antibody [ Time Frame: 3 year ]
    To assess the pharmacokinetic (PK) profile of ARX517 total antibody

  3. PK profile of ARX517-pAF-AS269 [ Time Frame: 3 years ]
    To assess the pharmacokinetic (PK) profile of ARX517 free payload pAF-AS269

  4. 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


Other Outcome Measures:
  1. 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

  2. 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

  3. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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


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

Locations
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United States, California
University of California Los Angeles School of Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: John Shen, M.D.         
Principal Investigator: John Shen, M.D.         
United States, Georgia
The Winship Cancer Institute of Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Mehmet Asim Bilen, M.D.         
Principal Investigator: Mehmet Asim Bilen, M.D.         
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Not yet recruiting
Indianapolis, Indiana, United States, 46202
Contact: Nabil Adra, M.D.         
Principal Investigator: Nabil Adra, M.D.         
United States, Michigan
University of Michigan Comprehensive Cancer Center Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Zachery Reichert, M.D.         
Principal Investigator: Zachery Reichert, M.D.         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Russell Pachynski, M.D.         
Principal Investigator: Russell Pachynski, M.D.         
United States, Nebraska
Urology Cancer Center, XCancer Research Network Recruiting
Omaha, Nebraska, United States, 68130
Contact: Luke Nordquist, M.D.         
Principal Investigator: Luke Nordquist, M.D.         
United States, New York
Weill Cornell Medical College Not yet recruiting
New York, New York, United States, 10065
Contact: Scott Tagawa, M.D.         
Principal Investigator: Scott Tagawa, M.D.         
United States, Washington
University of Washington Not yet recruiting
Seattle, Washington, United States, 98195
Contact: Michael Schweizer, M.D.         
Principal Investigator: Michael Schweizer, M.D.         
Sponsors and Collaborators
Ambrx, Inc.
Investigators
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Study Director: Ambrx Ambrx, Inc.
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Responsible Party: Ambrx, Inc.
ClinicalTrials.gov Identifier: NCT04662580    
Other Study ID Numbers: ARX517-2011
First Posted: December 10, 2020    Key Record Dates
Last Update Posted: August 27, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ambrx, Inc.:
Advanced Solid Tumor
ADC
Antibody drug conjugate
Prostate neoplasma
Castration-resistant
PSA increased
PSMA
Prostate specific membrane antigen
PSMA ADC
Prostate Cancer
Additional relevant MeSH terms:
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Neoplasms