A Study of FG-3246 in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Phase 2

Not yet recruiting

• Conditions: Metastatic Castration-Resistant Prostate Cancer
• Interventions: Drug: FG-3246

• Registration Number: NCT06842498
• Lead Sponsor: FibroGen

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of FG-3246, a cluster of differentiation 46 (CD46) targeting antibody-drug conjugate (ADC), in the treatment of participants with mCRPC who have progressed following treatment with one prior second-generation androgen receptor signaling inhibitor (ARSI) in any setting and no prior taxane therapy in the mCRPC setting.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-19
• Study First Submitted QC: 2025-02-19
• Status Verified: 2025-03
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-02
• Study Start: 2025-04-30
• Primary Completion: 2027-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 75

Inclusion Criteria

• Participant must have histological, and/or cytological confirmation of prostate adenocarcinoma (participants with pure small cell neuroendocrine carcinoma or mixed histology on prior or fresh tumor histologic evaluation of primary or metastatic lesion are excluded).
• Participant with safely accessible tumor lesion must agree to biopsy of a primary or metastatic lesion during screening. Alternatively, participant may provide an archival biopsy of a primary or metastatic lesion that was taken after castration resistance developed and within 1 year prior to randomization (if tumor biopsy is older than 1 year from randomization, discuss with the Medical Monitor). All biopsies will be sent to a central laboratory for review to confirm adenocarcinoma histology only and that there is adequate tumor for CD46 immunohistochemistry (IHC) testing. Participant with any non-adenocarcinoma histology or without adequate tumor on central review will be deemed ineligible for study participation. Participant with bone-only disease is excluded from this requirement.
• Participant must have serum testosterone levels <50 nanograms (ng)/deciliter (dL) during screening. Participant without a prior bilateral orchiectomy is required to remain on luteinizing hormone release hormone (LHRH) analog to maintain castrate levels of testosterone during the course of study participation.
• Participant is required to have progressed on one prior treatment with a second generation ARSI (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) initiated in either the castration-sensitive or castration-resistant setting.
• Participant must have progressive mCRPC following last treatment at screening.
• Participant must have ≥1 metastatic lesion that is present on baseline Computed Tomography (CT), Magnetic Resonance Imaging (MR)I, or bone scan obtained ≤28 days prior to randomization.
• Participant must have adequate organ function during screening and reconfirmed on Study Day -1 or Day 1.

Key

Exclusion Criteria

• Participant has received previous treatment with a therapeutic targeting CD46.
• Participant has small cell neuroendocrine carcinoma (pure or mixed) or any other non-adenocarcinoma component on prior or current histologic evaluation of primary or metastatic lesion.
• Participant has received more than one prior second-generation ARSI in any setting.
• Participant has received any systemic anticancer therapy (for example, immunotherapy, radioligand therapy, or biological therapy [including monoclonal antibodies]) within 28 days prior to randomization.
• Participant has received any prior radiation therapy within 28 days prior to randomization.
• Participant has a known actionable mutation or gene alteration, for example, BRCA1 mutation, for which approved therapies are available, for example, PARP inhibitors, unless these therapies are not appropriate for the participant as determined by the investigator or the participant refuses such therapy. Participant with one of these mutations who has already received targeted therapy and progressed on it is eligible.
• Participant has received any prior chemotherapy; however, one prior taxane-based chemotherapy in the castration-sensitive setting is allowed if completed >12 months before randomization. Participant treated with any other chemotherapies is excluded.
• Participant has known hypersensitivity to the components of FG-3246 or its analogs or a history of allergic or anaphylactic reaction to human, humanized, or chimeric monoclonal antibodies.
• Participant has diagnosis with any malignancy in the past 5 years, except for adequately treated basal cell or squamous cell carcinoma of the skin.
• Participant requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer drug that cannot be safely discontinued.

NOTE: Other protocol-defined inclusion/exclusion may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FG-3246 1.8 mg/kg	FG-3246	Participants will receive FG-3246 1.8 milligrams (mg)/kilogram (kg) administered via intravenous (IV) infusion on Day 1 of each 21-day treatment cycle (every 3 weeks \[Q3W\]) until radiographic progression, unacceptable safety and tolerability, participant or investigator decision to stop treatment, other withdrawal criteria are met, or FibroGen decision to close the study.
FG-3246 2.4 mg/kg	FG-3246	Participants will receive FG-3246 2.4 mg/kg administered via IV infusion on Day 1 of each 21-day treatment cycle (Q3W) until radiographic progression, unacceptable safety and tolerability, participant or investigator decision to stop treatment, other withdrawal criteria are met, or FibroGen decision to close the study.
FG-3246 2.7 mg/kg	FG-3246	Participants will receive FG-3246 2.7 mg/kg administered via IV infusion on Day 1 of each 21-day treatment cycle (Q3W) until radiographic progression, unacceptable safety and tolerability, participant or investigator decision to stop treatment, other withdrawal criteria are met, or FibroGen decision to close the study.

Primary Outcome Measures

Name	Time	Method
Radiographic Progression-free Survival (rPFS) by Investigator Assessment Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria	Until radiographic progression is noted (up to approximately 31 months)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From first dose until 28 days after last dose (up to approximately 31 months)
Maximum Plasma Concentration (Cmax) of FG-3246,Total Anticluster of Differentiation 46 Antibody (CD46), and Free Monomethyl Auristatin E (MMAE)	Within each 21 day treatment cycle from Cycle 1 through 28 days post last dose (up to approximately 31 months)

Secondary Outcome Measures

Name	Time	Method
rPFS Rate at 6 Months (rPFS6) by Investigator Assessment Per RECIST v1.1 and PCWG3 Criteria	Month 6
rPFS Rate at 12 Months (rPFS12) by Investigator Assessment Per RECIST v1.1 and PCWG3 Criteria	Month 12
Confirmed Objective Response Rate (ORR) by Investigator Assessment Per RECIST v1.1 and PCWG3 Criteria	From first dose up to approximately 31 months
Confirmed PSA50 Response Rate: Percentage of Participants Achieving a Decline in Prostate-specific Antigen (PSA) ≥50% From Baseline	Up to approximately 31 months
Confirmed PSA90 Response Rate: Percentage of Participants Achieving a Decline in PSA ≥90% From Baseline	Up to approximately 31 months
Composite Response Rate (CRR) by Investigator Assessment per RECIST 1.1 and PCWG3 Criteria	Up to approximately 31 months
PSA Progression-free Survival (PFS)	Up to approximately 31 months
Disease Control Rate (DCR) per RECIST 1.1 and PCWG3 Criteria	Up to approximately 31 months
Duration of Response (DoR) by Investigator Assessment Per RECIST v1.1 and PCWG3 Criteria	From first dose up to approximately 31 months
Clinical Benefit Rate (CBR) per RECIST 1.1 and PCWG3 Criteria	Up to approximately 31 months
Time to First Symptomatic Skeletal-related Event (SSRE)	Up to approximately 31 months
Percentage of Participants Who Develop Antidrug Antibodies (ADA) and Neutralizing Antibody (NAb) Against FG-3246	ithin each 21 day treatment cycle from Cycle 1 through 28 days post last dose (up to approximately 31 months)
Overall Survival (OS)	Until death or up to approximately 31 months

Trial Locations

Locations (1)

Astera Cancer Care; 🇺🇸 East Brunswick, New Jersey, United States