Trial of ARV-110 in Patients With Metastatic Castration Resistant Prostate Cancer

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Prostate Cancer Metastatic

Intervention / Treatment
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* Drug: ARV-110


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A: 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). Part B: 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: Part A: 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. Part B: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARV-110<br>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 | Drug: ARV-110<br>* Part A: Daily oral dosages are predetermined by cohort review committee after the initial starting dose cohort after the first 28 days of treatment Part B: Daily oral dosage and schedule at a recommended Phase 2 dose based on data from Part A<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Incidence of Dose Limiting Toxicities of ARV-110 | 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 | 28 Days | 
| Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-110 | Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug. | 28 Days | 
| Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-110 | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. | 28 Days | 
| Part B: Measurement of PSA response rate per PCWG3 accessing anti-tumor activity of ARV-110 | PSA response rate per PCWG3. | 12 Weeks | 
| Part B: Measurement of overall RECIST response rate accessing the anti-tumor activity of ARV-110 | Overall RECIST response rate in patients with measurable disease at baseline. | 12 Weeks | 
| Part B: To evaluate the clinical anti-tumor activity of ARV-110 in patients with mCRPC | 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. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | The anti-tumor activity of ARV-110 will be assessed by evaluating the overall PSA response per PCWG3. | 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. | The anti-tumor activity of ARV-110 will be assessed by evaluating the overall RECIST response rate. | 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. | The anti-tumor activity of ARV-110 will be assessed by evaluating the time to event progression free survival. | 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. | The anti-tumor activity of ARV-110 will be assessed by evaluating the duration of response. | 12 Weeks | 
| 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. | The anti-tumor activity of ARV-110 will be assessed by evaluating the time to progression. | 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. | The anti-tumor activity of ARV-110 will be assessed by evaluating the overall survival. | 12 Weeks | 
| Part A: Concentration-time curve (AUC) for single and multiple dose of ARV-110 | PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC). | 28 Days | 
| Part A: Maximum concentration (Cmax) for single and multiple dose of ARV-110 | PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter maximum concentration (Cmax). | 28 Days | 
| Part A: Minimum concentration (Cmin) for single and multiple dose of ARV-110 | PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter minimum concentration (Cmin). | 28 Days | 
| Part A: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110 | PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter time to maximum concentration (Tmax) | 28 Days | 
| Part B: Concentration-time curve (AUC) for single and multiple dose of ARV-110 | PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC). | 28 Days | 
| Part B: Maximum concentration (Cmax) for single and multiple dose of ARV-110 | PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter maximum concentration (Cmax). | 28 Days | 
| Part B: Minimum concentration (Cmin) for single and multiple dose of ARV-110 | PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter minimum concentration (Cmin). | 28 Days | 
| Part B: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110 | PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter time to maximum concentration (Tmax) | 28 Days | 
| Part B: Duration of response | From the date of first confirmed best overall response of CR or PR to the date of first progression per RECIST 1.1 or PCWG3, or death due to any cause without evidence of radiographic progression, whichever occurs first. | 12 Weeks | 
| Part B: Overall survival | Time interval from the date of first ARV-110 dose to the date of death due to any cause. | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Prostate Cancer, Castrate-Resistant, Prostate Cancer, mCRPC, adenocarcinoma of the prostate, bavdegalutamide