Several antibody-drug conjugates (ADCs) are emerging as promising treatments for metastatic castration-resistant prostate cancer (mCRPC). Here are some of the latest and most notable ADCs in development:
ARX517: This PSMA-directed ADC has shown encouraging preliminary results in the APEX-01 trial. In patients treated with higher doses (2 mg/kg or more), deep PSA reductions were observed, with PSA30, PSA50, and PSA90 rates of 61%, 52%, and 26% respectively. It demonstrated a favorable safety profile with common side effects being mild, such as dry mouth, dry eye, and fatigue (onclive.com/view/apex-01-lo....
MGC018: Directed against B7-H3, MGC018 has shown a 25% overall response rate in mCRPC patients in a phase 1 study. Common side effects included cytopenia and gastrointestinal issues. The ongoing TAMARACK study aims to further evaluate its efficacy compared to androgen receptor-targeted therapy (onclive.com/view/adcs-novel....
DS-7300: Another B7-H3-directed ADC, DS-7300, showed an overall response rate of 33% in a heavily pretreated mCRPC cohort. The median duration of response was 4.4 months, with notable toxicities including interstitial lung disease and cytopenia (onclive.com/view/adcs-novel....
Sacituzumab Govitecan (Trodelvy): Targeting Trop-2, this ADC has shown efficacy in other cancers and is being tested in mCRPC. In a phase 2 trial, it achieved a 6-month radiographic progression-free survival rate of 59%, with a median rPFS of 8.1 months (onclive.com/view/adcs-novel....
FOR46: This CD46-directed ADC showed promising results in a phase 1 trial with a PSA50 response rate of 37% and an overall response rate of 48%. Significant toxicities included neutropenia, but the drug displayed substantial clinical activity (onclive.com/view/adcs-novel....
These ADCs represent a new wave of targeted therapies for mCRPC, offering hope for better efficacy and tolerability in patients who have progressed on existing treatments. Further studies and clinical trials are ongoing to confirm these preliminary findings and potentially bring these treatments to broader clinical use.
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