What is the mechanism of action of this treatment?

Prostate cancer treatments often target the androgen receptor (AR) pathway, which is crucial for the growth and survival of prostate cancer cells. Common treatments include androgen deprivation therapy (ADT) that reduces androgen levels, and androgen receptor signaling inhibitors like enzalutamide and abiraterone, which block androgen binding or inhibit androgen production. PROTACs, such as ARV-110, represent a novel approach by promoting the degradation of the androgen receptor itself, potentially overcoming resistance mechanisms seen with traditional therapies. Understanding these mechanisms is vital for patients as it highlights the rationale behind treatment choices and the potential for newer therapies to improve outcomes.

What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as androgen receptor inhibitors like enzalutamide and abiraterone, have several known side effects. Enzalutamide can cause fatigue, anorexia, nausea, and a PSA flare in some patients. Abiraterone is associated with increased rates of hypertension and hypokalemia. Both drugs can also lead to cardiovascular toxicities and metabolic issues. Chemotherapy agents like docetaxel and cabazitaxel, which are also used in advanced prostate cancer, commonly cause fatigue, nausea, anemia, and elevated transaminases. These treatments may also lead to gastrointestinal issues such as constipation and diarrhea.

What prior FDA approvals exist?

Several FDA-approved treatments for prostate cancer target the androgen receptor pathway, similar to the investigational drug ARV-110. Enzalutamide and abiraterone are two prominent androgen receptor signaling inhibitors that have been approved for metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide works by inhibiting androgen receptor signaling, while abiraterone inhibits CYP17, an enzyme critical for androgen production. Additionally, apalutamide, another androgen receptor inhibitor, has been approved for metastatic castration-sensitive prostate cancer (mCSPC). These treatments have shown significant benefits in terms of overall survival and progression-free survival in clinical trials.

What other types of research exist?

Promising novel alternatives to ARV-110 for prostate cancer patients include: 1) Radium-223, an alpha particle-emitting agent that prolongs overall survival and decreases symptomatic skeletal-related events in men with castration-resistant prostate cancer (CRPC) and bone metastases. 2) Chimeric Antigen Receptor T-cell (CAR-T) therapies targeting prostate-specific membrane antigen (PSMA), such as P-PSMA-101. 3) Next-generation androgen receptor inhibitors like enzalutamide and abiraterone, which have shown efficacy even in some AR-V7 positive patients. 4) Immunotherapies, including checkpoint inhibitors and novel agents targeting specific tumor antigens. These alternatives represent cutting-edge approaches that may offer new hope for patients with advanced prostate cancer.

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Androgen Receptor Degrader

ARV-110 for Prostate Cancer (mCRPC Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Arvinas Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have ongoing ADT with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration).

Patients must have progressed on at least 2 prior approved systemic therapies for CRPC (at least one must be abiraterone or enzalutamide).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called ARV-110 to see if it is safe and can be tolerated by men with advanced prostate cancer that has not responded to other treatments. The drug aims to break down proteins that help cancer cells grow.

Who is the study for?

This trial is for men over 18 with advanced prostate cancer that's resistant to castration treatments. They should have progressed after systemic therapies but not had chemotherapy for their metastatic condition. Participants must be on hormone therapy or have had an orchiectomy, and can't have used more than two second-generation anti-androgens.

What is being tested?

The study tests ARV-110's safety and how well it's tolerated in different doses among men with metastatic castration-resistant prostate cancer (mCRPC). It targets those who've seen their disease progress despite previous treatments like enzalutamide or abiraterone.

What are the potential side effects?

Specific side effects of ARV-110 are not listed, but common ones may include fatigue, nausea, changes in appetite, skin reactions at the injection site, and potential hormonal imbalances due to its action on testosterone levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am currently on hormone therapy for cancer or have had an orchiectomy.

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My prostate cancer has worsened after two treatments, including abiraterone or enzalutamide.

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I have taken 1 or 2 treatments like enzalutamide or abiraterone for prostate cancer.

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I have had only one type of advanced hormone therapy for my prostate cancer.

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I have never received chemotherapy.

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I have had only one chemotherapy treatment for both early and advanced prostate cancer.

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My prostate cancer is advanced, has spread, and does not respond to hormone therapy.

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My prostate cancer is worsening despite treatment.

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I am a man and at least 18 years old.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part A: Incidence of Dose Limiting Toxicities of ARV-110

Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-110

Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-110

+3 more

Secondary study objectives

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.

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.

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.

+13 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: ARV-110Experimental Treatment1 Intervention

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

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target the androgen receptor (AR) pathway, which is crucial for the growth and survival of prostate cancer cells. Common treatments include androgen deprivation therapy (ADT) that reduces androgen levels, and androgen receptor signaling inhibitors like enzalutamide and abiraterone, which block androgen binding or inhibit androgen production. PROTACs, such as ARV-110, represent a novel approach by promoting the degradation of the androgen receptor itself, potentially overcoming resistance mechanisms seen with traditional therapies. Understanding these mechanisms is vital for patients as it highlights the rationale behind treatment choices and the potential for newer therapies to improve outcomes.

Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer.