An open-label, first-in-human study of SKB500 in patients with locally advanced or metastatic solid tumors.

Abstract

3011 Background: SKB500 is an antibody drug conjugate (ADC) composed of an antibody targeting the B7 homolog 3 (B7-H3), which is overexpressed in many types of solid tumors, conjugated to a topoisomerase I inhibitor payload via a cleavable pyrimidine-tripeptide linker. We hereby report initial results of the FIH study (NCT06736327). Methods: This phase 1 study comprised dose-escalation, dose-expansion, and indication-expansion phases to evaluate the safety, tolerability, pharmacokinetics, and efficacy of SKB500. Patients (pts) with unresectable solid tumors refractory to standard treatment will be enrolled and receive SKB500 at doses ranging from 2 to 18 mg/kg every three weeks (Q3W) until disease progression or unacceptable toxicity. The primary efficacy endpoint was objective response rate (ORR) assessed by investigators per RECIST v1.1. Results: As of Dec 23, 2025, 150 pts were treated with SKB500 across all dose levels (2-18 mg/kg). No dose-limiting toxicities (DLT) were observed during dose escalation. Based on preliminary data, the recommended phase 2 dose (RP2D) was established as 12 mg/kg. Among 97 pts treated at 12 mg/kg, the median treatment duration was 6.7 weeks. Treatment-related adverse events (TRAEs) occurred in 70 pts (72.2%), with most frequent (≥20%) being anemia (35.1%), nausea (34.0%), and white blood cell count decreased (24.7%). Grade ≥3 TRAEs occurred in 16 pts (16.5%), with most frequent being anemia, lymphocyte count decreased, pneumonia, and asthenia (each 3.1%). Pneumonitis occurred in 2 pts (2.1%; both grade 1). Both pneumonitis and grade ≥ 3 hematologic toxicities demonstrated low occurrence rates. No TRAEs led to treatment discontinuation or death. Among 55 pts treated at 12 mg/kg who had at least 6 weeks of follow-up (≥2 prior lines: 34.5%; prior platinum: 98.2%; prior IO therapy: 76.4%), the ORR was 54.5% (30/55) and the DCR was 92.7% (51/55). In tumor-specific subgroups, the small cell lung cancer (SCLC) cohort (n = 21) achieved an ORR of 71.4% (15/21) and a DCR of 100% (21/21), while the esophageal squamous cell carcinoma (ESCC) cohort (n = 18) showed an ORR of 55.6% (10/18) and a DCR of 88.9% (16/18). Conclusions: SKB500 demonstrated a manageable safety profile and promising antitumor activity in patients with treatment-refractory advanced solid tumors, with notable efficacy in SCLC and ESCC cohorts, supporting further clinical development. Clinical trial information: NCT06736327 .