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

NCT03575819 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: FOR46-001
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 5

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)

Conditions

Prostate Cancer Metastatic

Keywords

castration-resistant; androgen-signaling blockade progression

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Characterize FOR46 plasma concentration

  Through 1 month following last dose

• Characterize the FOR46 area under the curve

  Through 1 month following last dose

• Characterize FOR46 elimination

  Through 1 month following last dose

• Antidrug Antibodies

  Through 1 month following last dose

• Median radiographic progression-free survival

  12 months

Other Outcomes (1)

• Exploratory Endpoint: Tumor expression of CD46

  Through 1 month following last dose

Study Arms (2)

FOR46 (Dose Escalation)

EXPERIMENTAL

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 (Dose Expansion)

EXPERIMENTAL

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

Interventions

FOR46 DRUG

FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46

FOR46 (Dose Escalation); FOR46 (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Fortis Therapeutics, Inc.: lead

Study Sites (5)

UCLA Institute of Urologic Oncology

Los Angeles, California, 90095, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 06903, United States

Location

Related Publications (1)

• Aggarwal RR, Vuky J, VanderWeele D, Rettig M, Heath EI, Quigley D, Huang J, Chumber A, Cheung A, Foye A, Leung S, Abbey J, Dorr A, Nasoff M, Hunter J, Wang S, Flavell RR, Fong L, Liu B, Small EJ. Phase I, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients With Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2025 May 20;43(15):1824-1834. doi: 10.1200/JCO-24-01989. Epub 2025 Mar 26.

  PMID: 40138611 DERIVED

Study Officials

• Andrew Dorr, MD

  Fortis Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: July 3, 2018
• Study Start: February 4, 2019
• Primary Completion: November 16, 2023
• Study Completion: November 22, 2023
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)