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

Primary Purpose

Prostate Cancer Metastatic

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
FOR46
Sponsored by
Fortis Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer Metastatic focused on measuring castration-resistant, androgen-signaling blockade progression

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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)

Sites / Locations

  • UCLA Institute of Urologic Oncology
  • UCSF Helen Diller Family Comprehensive Cancer Center
  • Northwestern University
  • Karmanos Cancer Institute
  • OHSU Knight Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

FOR46 (Dose Escalation)

FOR46 (Dose Expansion)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Occurrence of toxicity
Type, incidence, severity, seriousness, and relatedness of adverse events.
Occurrence of dose-limiting toxicities
The severity and incidence of dose-limiting toxicities related to escalating dose levels of FOR46
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)

Secondary Outcome Measures

Characterize FOR46 plasma concentration
FOR46 maximum plasma concentration
Characterize the FOR46 area under the curve
FOR46 area under the plasma concentration-time curve
Characterize FOR46 elimination
FOR46 elimination half-life
Antidrug Antibodies
Change from baseline in serum levels of antidrug antibodies
Median radiographic progression-free survival
Assessed by Prostate Cancer Clinical Trials Working Group 3 criteria

Full Information

First Posted
June 20, 2018
Last Updated
April 29, 2023
Sponsor
Fortis Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03575819
Brief Title
A Phase 1 Study of FOR46 in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Official Title
A Phase 1 Study of FOR46 Administered Every 21 Days in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 4, 2019 (Actual)
Primary Completion Date
July 31, 2023 (Anticipated)
Study Completion Date
October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fortis Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer Metastatic
Keywords
castration-resistant, androgen-signaling blockade progression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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)
Allocation
Non-Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FOR46 (Dose Escalation)
Arm Type
Experimental
Arm Description
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.
Arm Title
FOR46 (Dose Expansion)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
FOR46
Intervention Description
FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46
Primary Outcome Measure Information:
Title
Occurrence of toxicity
Description
Type, incidence, severity, seriousness, and relatedness of adverse events.
Time Frame
Through 1 month following last dose
Title
Occurrence of dose-limiting toxicities
Description
The severity and incidence of dose-limiting toxicities related to escalating dose levels of FOR46
Time Frame
Through 1 month following last dose
Title
Disease response/composite response
Description
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)
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Characterize FOR46 plasma concentration
Description
FOR46 maximum plasma concentration
Time Frame
Through 1 month following last dose
Title
Characterize the FOR46 area under the curve
Description
FOR46 area under the plasma concentration-time curve
Time Frame
Through 1 month following last dose
Title
Characterize FOR46 elimination
Description
FOR46 elimination half-life
Time Frame
Through 1 month following last dose
Title
Antidrug Antibodies
Description
Change from baseline in serum levels of antidrug antibodies
Time Frame
Through 1 month following last dose
Title
Median radiographic progression-free survival
Description
Assessed by Prostate Cancer Clinical Trials Working Group 3 criteria
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Exploratory Endpoint: Tumor expression of CD46
Description
Association between level of tumor expression of CD46 by immunohistochemistry (IHC) analysis with clinical outcomes
Time Frame
Through 1 month following last dose

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Dorr, MD
Organizational Affiliation
Fortis Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Institute of Urologic Oncology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
OHSU Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
06903
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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