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FG-3246 for metastatic castration-resistant prostate cancer

A Phase 2 Dose Optimization Trial Evaluating a CD46-Targeted Antibody-Drug Conjugate (FG-3246) in Patients With Metastatic Castration-Resistant Prostate Cancer

Phase 2 Interventional Kyntra Bio · NCT06842498

This trial tests FG-3246, a CD46-targeting antibody-drug conjugate, in men with metastatic castration-resistant prostate cancer who progressed after one second-generation hormone therapy and have not received taxane chemotherapy for their metastatic disease.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment75 (estimated)
Ages18 Years and up
SexMale
SponsorKyntra Bio Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy, radiation
Locations15 sites (Tucson, Arizona and 14 other locations)
Trial IDNCT06842498 on ClinicalTrials.gov

What this trial studies

This is a phase 2, open-label interventional trial of FG-3246, a CD46-directed antibody-drug conjugate, in participants with metastatic castration-resistant prostate cancer (mCRPC). The study will measure safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity after participants who have progressed on one prior second-generation androgen receptor signaling inhibitor are treated with FG-3246. Participants must have castrate levels of testosterone, at least one metastatic lesion on imaging, and provide a fresh or recent archival tumor biopsy. The trial is being conducted at multiple U.S. oncology centers.

Who should consider this trial

Good fit: Ideal candidates are men with histologically confirmed mCRPC, castrate testosterone <50 ng/dL, progression after one second-generation ARSI, at least one measurable metastatic lesion, and willingness to provide a fresh or recent archival biopsy.

Not a fit: Patients who already received taxane chemotherapy for mCRPC, whose tumors lack CD46 expression, or who cannot undergo tumor biopsy are less likely to benefit.

Why it matters

Potential benefit: If successful, FG-3246 could shrink tumors or slow disease progression by delivering a targeted chemotherapy payload to CD46-expressing prostate cancer cells.

How similar studies have performed: Antibody-drug conjugates have shown activity in several cancers, but CD46-targeting ADCs like FG-3246 are relatively novel with limited published clinical efficacy data to date.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* Participant must have histological, and/or cytological confirmation of prostate adenocarcinoma.
* 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.
* Participant must have serum testosterone levels \<50 nanograms (ng)/deciliter (dL) during screening.
* 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 (MRI), 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, hormonal therapy, chemotherapy, immunotherapy, radioligand therapy, or biological therapy \[including monoclonal antibodies\], including investigational therapy) 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 has National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 2 peripheral neuropathy at the time of screening from any etiology.
* 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 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 other 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.

Where this trial is running

Tucson, Arizona and 14 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Castration-Resistant Prostate CancerFG-3246FOR46mCRPCCRPCCD46Prostate cancerAntibody-drug conjugate
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.