Promising early results of MHB088C (B7-H3 ADC) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) from a phase 1/2 multicenter study.

5051 Background: MHB088C is a novel B7-H3-targeted antibody-drug conjugate (ADC) incorporating the potent SuperTopoi payload, which is 5 to 10 times more potent than Dxd. Early data from an ongoing phase 1/2 study have shown that MHB088C is generally well tolerated, with early signs of clinical activity (ASCO 2024, abstract #3012). Here, we present preliminary findings from the subset of pts with mCRPC. Methods: This study consisted of 2 parts: dose-escalation (part 1) and expansion (part 2). Part 1 evaluated the safety and tolerability of MHB088C at doses ranging from 0.8 to 4.0 mg/kg, administered intravenously every 2 (Q2W) or 3 weeks (Q3W). Part 2 explored multiple doses to assess safety and prospective efficacy of MHB088C in selected tumor types, including mCRPC. Results: As of January 3, 2024, 36 pts with mCRPC were enrolled and received at least one dose of MHB088C (1.6~2.4 mg/kg, n=35; 3.0 mg/kg, n=1). The median age was 69 years (range: 51-83) and all pts had an ECOG performance status ≤1. These pts were heavily pretreated, with 100% having received novel androgen axis drugs (NAAD) and 80% having received docetaxel. The objective response rate (ORR) was 14.3%, and the disease control rate (DCR) was 95.2% in pts with measurable disease (n=21). At data cutoff, 19 pts (52.8%) remained on the treatment. Six-month radiographic progression-free survival (rPFS) was 87%. Preliminary data also indicate improvements in prostate-specific antigen (PSA) levels. Safety data were consistent with previous reports. The most common grade≥3 treatment-related adverse events were neutropenia (24.2%), platelet count decreased (11.1%) and anemia (15.2%). Conclusions: MHB088C demonstrated a manageable safety profile and promising anti-tumor activity in heavily pretreated pts with mCRPC. The preliminary safety and efficacy data are encouraging and warrant further investigation. Clinical trial information: CTR20231298 .