A Phase 1/2, Open-label, Dose Escalation, and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARV-110 in Patients With Metastatic Castration Resistant Prostate Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 248
- Locations
- 1
- Primary Endpoint
- Part A: Incidence of Dose Limiting Toxicities of ARV-110
Study Overview
Brief Summary
Phase 1/2 dose escalation study to assess the safety and tolerability of ARV-110 in men with mCRPC who have progressed on prior approved systemic therapies for their castrate resistant disease (one of which must be enzalutamide or abiraterone).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must be male and at least 18 years of age at the time of signing the informed consent.
- •Patients must present with histological, pathological, or cytological confirmed diagnosis of advanced or metastatic castration resistant adenocarcinoma of the prostate.
- •Patients must have progressed on at least 2 prior approved systemic therapies for CRPC (at least one must be abiraterone or enzalutamide).
- •Patients with progressive mCRPC
- •Patients must have ongoing ADT with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration).
- •Patients must be male and at least 18 years of age at the time of signing the informed consent.
- •Patients must present with histological, pathological, or cytological confirmed diagnosis of advanced or metastatic castration resistant adenocarcinoma of the prostate.
- •Patients must have received at least one but no more than two prior second generation anti-androgen agents (e.g., enzalutamide or abiraterone) for CRPC.
- •Patients must have received no more than one prior chemotherapy regimen in each of the following settings: castrate sensitive and castrate resistant prostate cancer.
- •Patients must have ongoing ADT with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration).
- •Part B - Phase 2 Expansion Cohort Subgroup 4
- •Patient has received only one prior AR second generation therapy (e.g., abiraterone or enzalutamide) either as treatment for CSPC or CRPC and no more than 1 regimen in CRPC setting.
- •No prior chemotherapy
Exclusion Criteria
- •Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses)
- •Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug.
- •Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study
- •Systemic anti cancer therapy within 2 weeks of first dose of study drug (6 weeks for bicalutamide, mitomycin C, or nitrosoureas and 4 weeks for abiraterone). Patients are ineligible if they received any other type of anti cancer agent (except agents to maintain castrate status) within 2 weeks before first dose of study drug.
- •Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses)
- •Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug.
- •Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study
- •Systemic anti cancer therapy within 2 weeks of first dose of study drug (6 weeks for bicalutamide, mitomycin C, or nitrosoureas and 4 weeks for abiraterone). Patients are ineligible if they received any other type of anti cancer agent (except agents to maintain castrate status) within 2 weeks before first dose of study drug.
Arms & Interventions
ARV-110
Part A: Oral tablet(s), once or twice daily in 28 day cycles
Part B: Oral tablet(s), once or twice daily in 28 day cycles
Intervention: ARV-110 (Drug)
Outcomes
Primary Outcomes
Part A: Incidence of Dose Limiting Toxicities of ARV-110
Time Frame: 28 Days
First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug
Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-110
Time Frame: 28 Days
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.
Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-110
Time Frame: 28 Days
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Part B: Measurement of PSA response rate per PCWG3 accessing anti-tumor activity of ARV-110
Time Frame: 12 Weeks
PSA response rate per PCWG3.
Part B: Measurement of overall RECIST response rate accessing the anti-tumor activity of ARV-110
Time Frame: 12 Weeks
Overall RECIST response rate in patients with measurable disease at baseline.
Part B: To evaluate the clinical anti-tumor activity of ARV-110 in patients with mCRPC
Time Frame: 12 Weeks
To evaluate the clinical anti-tumor activity (PSA response rate per PCWG3, Overall RECIST RR, rPFS, and PFS) of ARV-110 in patients with mCRPC in different subgroups of patients with mCRPC with predefined tumor genomic and molecular profiles or based on prior therapy.
Secondary Outcomes
- Part A: Anti-tumor activity based on the overall PSA response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
- Part A: Anti-tumor activity based on the overall RECIST response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
- Part A: Anti-tumor activity based on the progression free survival in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
- Part A: Anti-tumor activity based on the overall survival in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
- Part A: Anti-tumor activity based on the duration of response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
- Part A: Concentration-time curve (AUC) for single and multiple dose of ARV-110(28 Days)
- Part A: Anti-tumor activity based on the time to progression in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
- Part A: Maximum concentration (Cmax) for single and multiple dose of ARV-110(28 Days)
- Part A: Minimum concentration (Cmin) for single and multiple dose of ARV-110(28 Days)
- Part A: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110(28 Days)
- Part B: Concentration-time curve (AUC) for single and multiple dose of ARV-110(28 Days)
- Part B: Maximum concentration (Cmax) for single and multiple dose of ARV-110(28 Days)
- Part B: Minimum concentration (Cmin) for single and multiple dose of ARV-110(28 Days)
- Part B: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110(28 Days)
- Part B: Duration of response(12 Weeks)
- Part B: Overall survival(12 Weeks)