A Phase 1 clinical trial has unveiled encouraging results for FOR46 (FG-3246), a novel antibody-drug conjugate designed to combat metastatic castration-resistant prostate cancer (mCRPC). Published in the Journal of Clinical Oncology, the study indicates that FOR46 not only demonstrates a manageable safety profile but also exhibits significant clinical activity in patients who have exhausted conventional treatment options.
The therapy targets CD46, a protein found at high levels on prostate cancer cells that have progressed despite standard hormone therapies. The treatment links a potent chemotherapy payload to an antibody that specifically binds to CD46, aiming to reduce damage to healthy cells while enhancing tumor targeting.

The trial enrolled 56 men with advanced prostate cancer who had already received at least one prior androgen-signaling inhibitor. Researchers tested escalating doses of the drug, seeking the highest amount that patients could tolerate safely. The most common serious side effects included neutropenia (a drop in infection-fighting white blood cells), anemia, and fatigue. The recommended dose for future studies was determined to be 2.7 mg/kg based on adjusted body weight.

Among the 40 patients treated at or above the 1.2 mg/kg dose, results were encouraging. The median radiographic progression-free survival—a measure of how long patients lived without the disease worsening—was 8.7 months. In some cases, disease control lasted nearly three years.

Significantly, 36% of patients experienced at least a 50% decline in their PSA levels, a key marker of prostate cancer activity. The confirmed objective response rate was 20%, meaning that one in five patients saw their tumors shrink significantly, either partially or completely, as measured by imaging scans and clinical criteria.

Investigators also observed an increase in CD8+ T cells—the immune system’s cancer-fighting soldiers—suggesting that the therapy may not only attack tumors directly but also stimulate an immune response.

These findings offer cautious optimism for men with few treatment options left, as the therapy appears to be both biologically active and tolerable. Larger trials will be needed to confirm whether these early signals translate into longer survival or broader benefit across diverse patient groups.

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