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 with known PSMA Who Failed Prior Standard Therapies
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
Drug | Synonyms | Arms |
---|
ARX517 | | ARX517 Part 1 (Dose Escalation) |
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 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.
Trial Arms
Name | Type | Description | Interventions |
---|
ARX517 Part 1 (Dose Escalation) | Experimental | 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. | |
ARX517 Part 2 (Dose Expansion) | Experimental | 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. | |
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
August 27, 2021