A Phase 1 Study of FOR46 in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Study Overview
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Brief Summary
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This study will test the safety and efficacy of FOR46 given every 21 days to patients with metastatic castration-resistant prostate cancer. The name of the study drug involved in this study is: FOR46 for Injection (FOR46)

Detailed Description
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This study is designed to evaluate the safety, tolerability and antitumor activity of FOR46 in patients with metastatic castration-resistant prostate cancer. This study will be conducted in two parts: Dose escalation: This part will evaluate increasing doses of FOR46 to identify the maximum tolerated dose (MTD). The first patient enrolled on the study will receive the lowest dose of FOR46. Once this dose is shown to be safe, a second patient will be enrolled at the next higher dose. Patients will continue to be enrolled into either single or multiple patient groups receiving increasing doses until the MTD is reached. Dose expansion: This part of the study will further evaluate the safety, tolerability and antitumor activity of FOR46 at a dose shown to be safe in the dose escalation part of the study. Patients will be enrolled into 1 of 2 groups, based on histology.

Official Title
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A Phase 1 Study of FOR46 Administered Every 21 Days in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Conditions
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Prostate Cancer Metastatic

Intervention / Treatment
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* Drug: FOR46


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male ≥ 18 years of age Has histologically confirmed prostate cancer that is metastatic and has progressed as defined by PCWG3 criteria during or after treatment with at least 1 ASI (eg, abiraterone, enzalutamide, apalutamide), or another second-generation anti-androgen or cytochrome P450 (CYP)17A1 inhibitor, with the most recent ASI administered in the castration-resistant setting Has serum testosterone levels < 50 ng/dL during screening. Patients without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analog during the course of protocol therapy ECOG performance status of 0 or 1 Adequate hematologic, renal and hepatic function Males with female partners of childbearing potential must agree to use 2 effective methods of contraception Patients must provide signed informed consent Patients enrolled into the dose expansion phase must have prostate carcinoma without histologic evidence of small-cell/neuroendocrine carcinoma features on prior biopsy or must have unequivocal histologic evidence of small-cell/neuroendocrine prostate carcinoma (pure or mixed). Patients with treatment-emergent small-cell neuroendocrine cancer (pure or mixed) may have received no more than on prior chemotherapy regimen for mCRPC Patients enrolled into the dose expansion phase must be willing to undergo a metastatic tumor biopsy or has tissue available from a prior post-castration resistant tumor biopsy Exclusion Criteria: Persistent clinically significant toxicities from previous anticancer therapy Has NCI CTCAE Grade ≥ 2 peripheral neuropathy from any etiology or has a genetic disorder that is associated with peripheral neuropathy even without current neuropathic manifestations Prior treatment with cytotoxic chemotherapy for mCRPC (chemotherapy in the hormone-sensitive setting is allowed if > 6 months before study entry) Has received external-beam radiation or systemic anticancer therapy within 14 days before first dose of FOR46 Has received treatment with an investigational drug within 28 days before first dose of FOR46 Has had a major surgical procedure within 28 days before administration of FOR46 dose Clinically significant cardiovascular disease Uncontrolled, clinically significant pulmonary disease Has a history of brain or leptomeningeal metastases. Uncontrolled intercurrent illness Has a known positive status for HIV or either active/chronic hepatitis B/C Requires medications that are strong inhibitors or strong inducers of CYP3A4 [Dose escalation only] Has a history of episodic atrial fibrillation or flutter (patients with chronic atrial fibrillation are not excluded)

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Following completion of the dose escalation phase of the study and determination of a recommended phase 2 dose, patients will be enrolled into a dose expansion cohort.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOR46 (Dose Escalation)<br>Eligible patients will receive FOR46 administered as an IV infusion every 21 days. Patients will be enrolled into escalating dose levels during the Dose Escalation period of the study. | Drug: FOR46<br>* FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46<br>|
| Experimental: FOR46 (Dose Expansion)<br>Eligible patients will receive FOR46 administered as an IV infusion every 21 days. Patients will receive the maximum tolerated dose during the Dose Expansion period of the study. | Drug: FOR46<br>* FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of toxicity | Type, incidence, severity, seriousness, and relatedness of adverse events. | Through 1 month following last dose | 
| Occurrence of dose-limiting toxicities | The severity and incidence of dose-limiting toxicities related to escalating dose levels of FOR46 | Through 1 month following last dose | 
| Disease response/composite response | Decline in serum prostate-specific antigen greater than 50% from baseline, confirmed by repeat measurement and objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize FOR46 plasma concentration | FOR46 maximum plasma concentration | Through 1 month following last dose | 
| Characterize the FOR46 area under the curve | FOR46 area under the plasma concentration-time curve | Through 1 month following last dose | 
| Characterize FOR46 elimination | FOR46 elimination half-life | Through 1 month following last dose | 
| Antidrug Antibodies | Change from baseline in serum levels of antidrug antibodies | Through 1 month following last dose | 
| Median radiographic progression-free survival | Assessed by Prostate Cancer Clinical Trials Working Group 3 criteria | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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castration-resistant, androgen-signaling blockade progression