Clinical Trials /

ARX517 in Subjects With Advanced Solid Tumor

NCT04662580

Description:

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 Who Failed Prior Standard Therapies

Related Conditions:
  • Adenocarcinoma
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: ARX517 in Subjects With Advanced Solid Tumor
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ARX517-2011
  • NCT ID: NCT04662580

Conditions

  • Advanced Solid Tumor
  • Solid Neoplasm

Interventions

DrugSynonymsArms
ARX517Part 1: Cohort 1

Purpose

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Cohort 1ExperimentalCohort 1 will administer Dose Level 1 (0.32 mg/kg) of ARX517 every 3 weeks (Q3W) via intravenous infusion.
  • ARX517
Part 1: Cohort 2ExperimentalCohort 2 will administer Dose Level 2 (0.64 mg/kg of ARX517 every 3 weeks (Q3W) via intravenous infusion.
  • ARX517
Part 1: Cohort 3ExperimentalCohort 3 will administer Dose Level 3 (1.07 mg/kg of ARX517 every 3 weeks (Q3W) via intravenous infusion.
  • ARX517
Part 1: Cohort 4ExperimentalCohort 4 will administer Dose Level 4 (1.4 mg/kg of ARX517 every 3 weeks (Q3W) via intravenous infusion.
  • ARX517
Part 1: Cohort 5ExperimentalCohort 5 will administer Dose Level 5 (1.7 mg/kg of ARX517 every 3 weeks (Q3W) via intravenous infusion.
  • ARX517
Part 1: Cohort 6ExperimentalCohort 6 will administer Dose Level 6 (2.0 mg/kg of ARX517 every 3 weeks (Q3W) via intravenous infusion.
  • ARX517

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The primary objectives of Part 1: Safety and tolerability of ARX517
Time Frame:1.5 Years
Safety Issue:
Description:The primary objectives of Part 1 are: • To assess and establish the safety and tolerability of ARX517

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ambrx, Inc.

Trial Keywords

  • Advanced Solid Tumor
  • ADC
  • Antibody drug conjugate
  • Prostate neoplasma
  • Castration-resistant
  • PSA increased
  • PSMA
  • Prostate specific membrane antigen
  • PSMA ADC
  • Prostate Cancer

Last Updated

June 10, 2021