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

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

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)

Study Overview

• Status: Completed
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Drug: FOR46

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Institute of Urologic Oncology
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 06903
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FOR46 (Dose Escalation); 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; FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46
Experimental: FOR46 (Dose Expansion); 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; FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Occurrence of toxicity	Type, incidence, severity, seriousness, and relatedness of adverse events.	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoint: Tumor expression of CD46	Association between level of tumor expression of CD46 by immunohistochemistry (IHC) analysis with clinical outcomes	Through 1 month following last dose

Collaborators and Investigators

• Sponsor: Fortis Therapeutics, Inc.
• Investigators: Study Director: Andrew Dorr, MD, Fortis Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2019
• Primary Completion (Actual): November 16, 2023
• Study Completion (Actual): November 22, 2023

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: June 29, 2018
• First Posted (Actual): July 3, 2018

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: castration-resistant; androgen-signaling blockade progression
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: FOR46-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No