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
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
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.
Advanced Solid Tumor Solid Neoplasm ADC Antibody drug conjugate Prostate neoplasma Castration-resistant PSA increased PSMA Prostate specific membrane antigen PSMA ADC Prostate Cancer Neoplasms ARX517
You can join if…
Open to people ages 18 years and up
- Male subjects ≥18 years at the time of providing written informed consent
- Pathologically confirmed adenocarcinoma of the prostate or other solid tumors
- For prostate cancer, ongoing therapy with a gonadotropin-releasing hormone agonist or antagonist AND serum testosterone level <50 ng/dL at Screening
- For prostate cancer, prior treatment with at least 2 Food and Drug Administration (FDA) approved treatments for metastatic castration-resistant prostate cancer.
- 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
- 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:
- 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)
- Radiographic progression (CT/MRI) by Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) criteria
- Nuclear scan progression by new lesions
- 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.
- Discontinuation of radiotherapy >4 weeks prior
- Eastern Cooperative Oncology Group performance status of 0 to 1 at Screening
- . Adequate organ function with following blood counts at Screening:
- . Adequate organ function with following Chemistry values at Screening:
- . Life expectancy of at least 6 months at Screening as per Investigator's judgment
- . Willing and able to provide written informed consent for participation in the study, and comply with all protocol requirements and assessments
- . 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.
You CAN'T join if...
- History of allergic reactions to any component of the ARX517.
- Impaired pituitary or adrenal gland function (e.g., Addison's disease, Cushing's syndrome)
- 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
- Therapy with estrogen within 30 days prior to the start of study drug
- 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
- 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
- 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
- History of other malignancy within the previous 2 years (no longer being actively treated), except basal cell carcinoma
- 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
- . Blood transfusion within 30 days of Screening
- . Serious and /or persistent infection within 14 days of the start of study drug
- . Treatment with any investigational drug within 4 weeks prior to Day 1 of the study
- . 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)
- . 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.
- . Prior history of clinically significant ocular events, or any current ongoing active ocular infections.
- . 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.
- University of California Los Angeles School of Medicine
accepting new patients
Los Angeles California 90095 United States
- University of Washington
not yet accepting patients
Seattle Washington 98195 United States
Lead Scientist at University of California Health
- John Shen, M.D. (ucla)
HS Assistant Clinical Professor, Medicine.
- accepting new patients
- Start Date
- Completion Date
- Ambrx, Inc.
- Phase 1
- Study Type
- Last Updated