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

Arvinas Inc.248 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

248

Conditions

Prostate Cancer Metastatic

Interventions

ARV-110DRUG

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

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (54)

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: 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.

Time frame: 28 Days

Part B: Measurement of PSA response rate per PCWG3 accessing anti-tumor activity of ARV-110

PSA response rate per PCWG3.

Time frame: 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.

Time frame: 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.

Time frame: 12 Weeks

Secondary Outcomes

Data from ClinicalTrials.gov

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Clinical Trial Site

Los Angeles, California, United States

Clinical Trial Site

Orange, California, United States

Clinical Trial Site

San Francisco, California, United States

Clinical Trial Site

New Haven, Connecticut, United States

Clinical Trial Site

Altamonte Springs, Florida, United States

Clinical Trial Site

Bonita Springs, Florida, United States

Clinical Trial Site

Bradenton, Florida, United States

Clinical Trial Site

Brandon, Florida, United States

Clinical Trial Site

Cape Coral, Florida, United States

Clinical Trial Site

Clearwater, Florida, United States

...and 44 more locations

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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)

Time frame: 28 Days

Part B: Concentration-time curve (AUC) for single and multiple dose of ARV-110

Time frame: 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).

Time frame: 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).

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 12 Weeks