Safety and efficacy of QLC5508 (MHB088C) in heavily-treated patients with metastatic castration-resistant prostate cancer: Updated data from a phase 1/2 trial.

5046 Background: QLC5508 (MHB088C), a novel B7-H3-targeted antibody-drug conjugate with high cell-binding activity and internalization rate, contains SuperTopoi payload which is 5 to 10 times more potent than Dxd. The preliminary data of a phase 1 study indicated the promising anti-tumor activity and tolerability of QLC5508 in patients (pts) with solid tumors, including metastatic castration-resistant prostate cancer (mCRPC). Here we report the updated results of efficacy and safety in pts with mCRPC. Methods: This multi-center phase 1/2 trial consisted of dose-escalation stage and dose-expansion stage. In dose-escalation stage, QLC5508 was administered via intravenous infusion at dosage ranging from 0.8 mg/kg to 4.0 mg/kg every two (Q2W) or three weeks (Q3W) in pts with various advanced solid tumors. Then, pts with mCRPC were recruited if they failed or intolerable to standard treatment, including second-generation androgen receptor pathway inhibitors (ARPIs) and/or taxane-based chemotherapy. Dose levels of 1.6 mg/kg Q2W, 2.0 mg/kg Q2W, and 2.4 mg/kg Q3W were selected. The primary endpoints were safety and tolerability. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and radiological progression-free survival (rPFS) per RECIST v1.1 and PCWG3, and prostate-specific antigen (PSA) response rate. Results: As of Nov 30, 2025, 59 pts were enrolled (≥3 lines of prior treatment: 74.6%; ≥3 lines of prior second-generation ARPIs: 28.8%; prior taxane: 84.7%; ≥2 lines of prior taxane: 16.9%). Grade ≥3 treatment-emergent adverse events (TEAEs) with incidence of > 20% were neutrophil count decreased (25.4%), anemia (23.7%), and white blood cell decreased (20.3%). Grade ≥3 gastrointestinal TEAEs occurred in two (3.4%) pts, both unrelated to the treatment. Intestinal lung disease occurred in one (1.7%) patient from 1.6 mg/kg Q2W dose level. TEAEs leading to treatment discontinuation and dose reduction occurred in one (1.7%) and six (10.2%) pts, respectively. The median rPFS was not reached (95% confidence interval [CI], 13.11-not evaluable [NE]), and the 12-month rPFS rate was 71.7% (95% CI, 52.55%-84.26%). In 38 pts at 2.0 mg/kg Q2W dose level, the median rPFS was not reached (95% CI, 13.11-NE), and 12-month rPFS rate was 78.6% (95% CI, 50.67%-91.80%). In 31 pts at 2.0 mg/kg Q2W dose level who had received prior second-generation ARPIs and taxane, the median rPFS was 13.11 months (95% CI, NE-NE). In 31 pts with target lesion at baseline, confirmed ORR and DCR was 22.6% (95% CI, 9.6%-41.1%) and 96.8% (95% CI, 83.3%-99.9%), respectively. Thirteen pts (22.8%) achieved PSA 50 response. Conclusions: QLC5508 showed prolonged rPFS as well as manageable safety profile in heavily treated pts with mCRPC. A phase 3 study is currently being planned. Clinical trial information: NCT07102004 .