What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as androgen receptor inhibitors like Enzalutamide, can cause side effects including fatigue, gynecomastia, and seizures. Apalutamide and darolutamide have similar side effects but may have fewer central nervous system toxicities. Abiraterone, often used with prednisone, can lead to fluid retention, hypokalemia, and hypertension. Chemotherapy agents like docetaxel, used with ADT, can result in severe myelosuppression and other serious adverse events.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of prostate cancer, particularly focusing on androgen receptor inhibition. Enzalutamide, apalutamide, and darolutamide are notable androgen receptor inhibitors that block androgen binding, inhibit nuclear translocation, and prevent DNA association. These drugs do not require concurrent steroid treatment, unlike abiraterone, which also targets androgen pathways but necessitates steroid use. While FOR46, targeting CD46, is still under investigation, these androgen receptor inhibitors have established efficacy in treating metastatic castration-resistant prostate cancer (mCRPC).

What other types of research exist?

Promising novel alternatives for prostate cancer treatment in 2024 include: 1) Darolutamide, which has shown efficacy in enzalutamide-resistant prostate cancer, particularly in cases with mutated androgen receptors. 2) Apalutamide, which has demonstrated improved overall survival in metastatic castration-sensitive prostate cancer. 3) Lutetium-177-PSMA-617, a radioligand therapy targeting PSMA-positive metastatic castration-resistant prostate cancer, showing significant efficacy in clinical trials.

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Hormone Therapy

FOR46 + Enzalutamide for Prostate Cancer

Q: What is the mechanism of action of this treatment?

Prostate cancer treatments often target the androgen receptor (AR) pathway, crucial for prostate cancer cell growth. Enzalutamide, a second-generation AR inhibitor, blocks androgen binding, AR nuclear translocation, and AR-DNA binding, effectively reducing cancer cell proliferation. This is significant for patients as it directly impedes the cancer's growth mechanism. FOR46, an investigational agent, targets CD46, a protein overexpressed in many cancers, including prostate cancer. By binding to CD46, FOR46 aims to disrupt cancer cell survival pathways. These mechanisms are vital as they offer targeted approaches to hinder cancer progression, potentially improving patient outcomes and providing options when resistance to other treatments develops.

Phase 1 & 2

Recruiting

Led By Rahul Aggarwal, MD

Research Sponsored by Rahul Aggarwal

Eligibility Criteria Checklist

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

Must have

Patients must be evaluable for the primary endpoint of composite response, and must have either serum PSA ≥ 2 ng/mL during Screening and/or measurable disease by RECIST 1.1 criteria

Histologically confirmed metastatic prostate adenocarcinoma

Must not have

Cardiac condition as defined as one or more of the following: Uncontrolled supraventricular arrhythmia or ventricular arrhythmia requiring treatment, New York Heart Association (NYHA) congestive heart failure class III or IV, History of unstable angina, myocardial infarction, or cerebrovascular accident within 6 months prior to Cycle 1, Day 1

Use of a prohibited concomitant medication within 7 days of first dose of FOR46, including: Strong inhibitor of CYP3A4 (boceprevir, clarithromycin, cobicistat, conivaptan, diltiazem, danoprevir/ritonavir, elvitegravir/ritonavir, grapefruit juice, idelalisib, indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir/ritonavir/ombitasvir and/or dasabuvir, posaconazole, ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, troleandomycin, and voriconazole

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, FOR46, combined with enzalutamide in patients with advanced prostate cancer that hasn't responded to other treatments. FOR46 targets cancer cells directly, and enzalutamide blocks hormones that help the cancer grow. Enzalutamide is approved for the treatment of advanced prostate cancer and has shown effectiveness in prolonging survival.

Who is the study for?

Men with metastatic castration-resistant prostate cancer who've progressed after abiraterone treatment. They must not have had other systemic anti-cancer therapies recently, no prior CD46-targeting treatments, and should be in good physical condition (ECOG <=1). Adequate organ function is required, and they can't have brain metastases or certain heart conditions. Participants need to agree to use contraception.

What is being tested?

The trial tests FOR46 combined with enzalutamide against prostate cancer that resists standard hormone therapy. FOR46 targets a protein called CD46 on cancer cells. The study aims to see if this combination improves response rates and how long patients benefit from the treatment.

What are the potential side effects?

Potential side effects may include immune reactions due to FOR46 targeting CD46 on normal cells, fatigue, blood cell count changes from Pegfilgrastim, and hormonal side effects like hot flashes or sexual dysfunction from Enzalutamide.

Eligibility Criteria

Inclusion Criteria

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

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My PSA level is 2 ng/mL or higher, or my cancer can be measured using specific criteria.

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My prostate cancer has spread and was confirmed by a biopsy.

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My testosterone levels are very low, and I am on or will stay on hormone therapy if I haven't had surgery to remove my testicles.

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I am 18 years old or older.

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My prostate cancer has worsened despite treatment with specific hormone therapies.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious heart condition or recent heart attack or stroke.

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I haven't taken any strong medication that affects liver enzymes in the last week.

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I am taking more than 10mg of steroids or other immunosuppressants daily.

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I have a history of seizures or conditions like brain metastasis, stroke, brain bleeding, or lung inflammation.

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I have previously been treated with FOR46 or a similar medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Composite response rate (CRR) (Phase 2)

Maximally tolerated dose (MTD) (Phase 1b)

Number of participants with Dose-Limiting Toxicities (Phase 1b)

Secondary study objectives

Frequency of treatment-related, adverse events (AE)

Median duration of objective response

Median overall survival survival.

+4 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dose ExpansionExperimental Treatment3 Interventions

Participants will receive a lead-in treatment period of enzalutamide monotherapy for 14 days (day -14 to day -1), followed by addition of FOR46 on Cycle 1 Day 1, at the maximum tolerated dose (MTD) as determined in Phase 1b. If participants are on enzalutamide at the time of study entry, and remain on continuous dosing at 160 mg daily, the lead-in treatment period will not be required. Prophylactic Pegfilgrastim (G-CSF) 6mg, subcutaneously (SQ) will also be administered on Day 2 during all treatment cycles. Pegfilgrastim could be modified to a lower dose of 3 mg with treating investigator approval.

Group II: Does EscalationExperimental Treatment4 Interventions

Approximately 3 dose levels of FOR46 will be evaluated. Participants will receive a lead-in treatment period of enzalutamide monotherapy for 14 days (day -14 to day -1), followed by addition of FOR46 on Cycle 1 Day 1. If participants are on enzalutamide at the time of study entry, and remain on continuous dosing at 160 mg daily, the lead-in treatment period will not be required. Prophylactic Pegfilgrastim (G-CSF) 6mg, subcutaneously (SQ) will also be administered on Day 2 during all treatment cycles. Pegfilgrastim could be modified to a lower dose of 3 mg with treating investigator approval.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Blood Samples

2003

N/A

~410

FOR46

2019

Completed Phase 1

~90

Enzalutamide

2014

Completed Phase 4

~3820

Pegfilgrastim

2013

Completed Phase 3

~4440

0 / 10Eligibility 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, crucial for prostate cancer cell growth. Enzalutamide, a second-generation AR inhibitor, blocks androgen binding, AR nuclear translocation, and AR-DNA binding, effectively reducing cancer cell proliferation. This is significant for patients as it directly impedes the cancer's growth mechanism. FOR46, an investigational agent, targets CD46, a protein overexpressed in many cancers, including prostate cancer. By binding to CD46, FOR46 aims to disrupt cancer cell survival pathways. These mechanisms are vital as they offer targeted approaches to hinder cancer progression, potentially improving patient outcomes and providing options when resistance to other treatments develops.