FOR46 in Combination With Enzalutamide in Patients With Metastatic Castration Resistant Prostate Cancer

NCT05011188 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 21555NCI-2021-08857
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1b/2 study evaluating FOR46 in combination with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) after prior progression on abiraterone. FOR46 is designed to target and bind to CD46, a transmembrane cellular protein expressed at moderate or high levels in numerous cancer types. The investigators hypothesize that the combination of FOR46 plus enzalutamide will achieve a clinically significant composite response rate with sufficient durability of response in mCRPC patients.

Conditions

Metastatic Castration-resistant Prostate Cancer; Prostate Cancer

Keywords

FOR46; Enzalutamide

Outcome Measures

Primary Outcomes (3)

• Maximally tolerated dose (MTD) (Phase 1b)

  A minimum of 3 patients will be treated at each dose level. If \< 33%of patients (i.e. 0 of 3 patients, or 1 of 6 patients) within a cohort have a dose-limiting toxicity (DLT in Cycle 1, then enrollment of the next cohort may commence upon approval of Data and Safety Monitoring Committee. At any dose level, dose escalation will be discontinued if \>= 2 of 3 to 6 patients within a cohort experience a DLT in Cycle 1, the MTD will have been exceeded. The previous dose level will then be considered the MTD if 6 patients were previously evaluated at this dose level. If this dose level was previously evaluated with 3 patients, then 3 additional patients will be enrolled at this dose level; if 0 or 1 of the additional 3 patients experiences a DLT in Cycle 1, then this dose level will be considered the MTD.

  Up to 3 weeks

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

  Dose-limiting toxicities classified using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0will be tabulated by dose level and reported in descriptive fashion.

  Up to 3 weeks

• Composite response rate (CRR) (Phase 2)

  Composite response is defined as a \>= 50% decline from baseline PSA (defined by Cycle 1 Day 1 value), confirmed by repeat measurement \>= 4 weeks later AND/OR objective tumor response by RECIST 1.1 criteria The composite response rate along with 95% confidence interval will be reported

  Up to 2 years

Secondary Outcomes (7)

• Proportion of participants with a greater than or equal to 50% change in PSA (PSA50)

  Up to 2 years

• Objective response rate (ORR)

  Up to 2 years

• Median duration of objective response

  Up to 2 years

• Median time to PSA progression

  Up to 2 years

• Median radiographic progression-free survival

  Up to 2 years

Study Arms (2)

Does Escalation

EXPERIMENTAL

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.

Biological: FOR46; Biological: Enzalutamide; Drug: Pegfilgrastim; Procedure: Blood Samples

Dose Expansion

EXPERIMENTAL

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.

Biological: FOR46; Biological: Enzalutamide; Drug: Pegfilgrastim

Interventions

FOR46 BIOLOGICAL

Given intravenously (IV)

Also known as: Antibody-Drug Conjugate (ADC), anti-CD46 antibody conjugate

Does Escalation; Dose Expansion

Enzalutamide BIOLOGICAL

Given orally (PO)

Also known as: XTANDI

Does Escalation; Dose Expansion

Pegfilgrastim DRUG

Given subcutaneously (subQ)

Also known as: G-CSF

Does Escalation; Dose Expansion

Blood Samples PROCEDURE

Blood samples will be taken for correlative studies

Also known as: Blood Specimen, Biospecimen

Does Escalation

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed metastatic prostate adenocarcinoma.
• Disease progression by PCWG3 criteria at study entry.
• Prior progression by PCWG3 criteria on one or more androgen signaling inhibitors including abiraterone acetate, enzalutamide, apalutamide, and/or darolutamide.
• No prior taxane-based chemotherapy for the treatment of mCRPC. Prior taxane use in the castration-sensitive prostate cancer (CSPC) setting allowed provided last dose \> 6 months prior to study entry.
• 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.
• Participants must be willing to undergo metastatic tumor biopsy during Screening. If there is no safely accessible metastatic lesion, this requirement will be waived.
• Dose Expansion only: Participants must be willing to undergo CD46-directed Positron Emission Tomography (PET) imaging during Screening (Co-enrolling on NCT05245006, Groups B and C)
• Castrate level of serum testosterone at study entry (\<50 ng/dL). Patients without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study.
• No other systemic anti-cancer therapies administered other than LHRH analogue within 14 days or, 5 half-lives, whichever is shorter, prior to initiation of study treatment. Adverse events related to prior anti-cancer treatment related to therapies other than LHRH analogue must have recovered to Grade ≤ 1 with the exception of any grade alopecia. a. Patients receiving enzalutamide prior to study entry may continue treatment at their current enzalutamide dose level without requirement for wash-out period.
• Age \>=18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky performance status \>= 70 percent (%)).
• Demonstrates adequate organ function as defined below:
• Absolute neutrophil count ≥ 1,500/microliter (mcL).
• Platelets \>= 100,000/mcL and no platelet transfusions during the 14 days prior to first dose of FOR46.
• Hemoglobin \>= 8.0 grams per deciliter (g/dL) without red blood cell transfusion during the 14 days prior to first dose of FOR46.

You may not qualify if:

• Has received prior radiotherapy within 2 weeks of first dose of FOR46.
• Prior treatment with FOR46 or another CD46-targeting therapeutic agent.
• Prior histologic evidence of de novo or treatment-emergent small cell neuroendocrine prostate cancer. Pathologic assessment of baseline tumor biopsy performed during Screening is not required for determination of study eligibility.
• 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.
• History of seizure or pre-disposing condition including:
• History of brain metastasis.
• Cerebrovascular accident (CVA) within 6 months prior to study entry.
• History of intracranial hemorrhage.
• History of pneumonitis.
• Is receiving systemic steroid therapy at a prednisone equivalent dose of \> 10 milligram daily or other form of immunosuppressive therapy within 7 days prior to first dose of study drug.
• Has an active infection requiring intravenous antibiotics within 7 days prior to Cycle 1, Day 1.
• Use of a prohibited concomitant medication within 7 days of first dose of FOR46, including:

Sponsors & Collaborators

• Rahul Aggarwal: lead
• Fortis Therapeutics, Inc.: collaborator
• Kyntra Bio: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Immunoconjugates; enzalutamide; pegfilgrastim; Granulocyte Colony-Stimulating Factor; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Rahul Aggarwal, MD

  University of San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 18, 2021
• Study Start: January 19, 2022
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)