Clinical Summary:

• Design/Population: This multicenter, open-label, phase 1 trial evaluated SKB500, a B7-H3-directed antibody-drug conjugate, at doses of 12 mg/kg and 16 mg/kg in heavily pretreated patients with unresectable small cell lung cancer. 
• Key Outcomes: SKB500 demonstrated an overall objective response rate of 67.2%, with higher response rates and fewer grade ≥3 treatment-related adverse events at 12mg/kg compared with 16 mg/kg. Median progression-free survival was 7.2 months and 5.6 months, respectively. 
• Clinical Relevance: These findings support further development of SKB500 as a potential treatment option, with the 12 mg/kg dose demonstrating a more favorable preliminary efficacy and safety profile. Additional studies are needed to confirm these findings and clarify potential predictive biomarkers.

Updated results from a phase 1 trial demonstrated promising antitumor activity with SKB500, a B7-H3-directed antibody-drug conjugate, in heavily pretreated patients with unresectable small cell lung cancer (SCLC), with the 12 mg/kg dose showing higher response and fewer severe treatment-related adverse events compared with the 16 mg/kg dose. 

These findings were presented by Haifeng Liu, MD, Jilin Cancer Hospital, Changchun, China, at the European Society for Medical Oncology (ESMO) Congress. 

In this multicenter, open-label trial, 61 patients who previously received platinum-based therapy received either 12 mg/kg (n = 40) or 16 mg/kg (n = 21) of SKB500 every 3 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR), assessed via investigator according to RECIST version 1.1. Key secondary end points include disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and safety. 

At a median follow-up of 4.6 months, all 61 patients had received treatment and had at least 6 weeks of follow-up. The overall ORR was 67.2%, with responses observed in 70% of patients receiving 12 mg/kg and 61.9% of patients receiving 16 mg/kg. Confirmed response rates were 55% and 47.6%, respectively.

The disease control rate was 95% in patients receiving 12 mg/kg and 81% in patients receiving 16 mg/kg. Median duration of response was 5.8 months in both treatment arms. 

Median PFS was 7.2 months in patients receiving 12 mg/kg and 5.6 months in patients receiving 16 mg/kg, with 6-month PFS rates of 57.6% and 41.8%, respectively. Median OS had not been reached in either treatment arm. The estimated 6-month OS rate was 84.2% in patients receiving 12 mg/kg and 60.2% in patients receiving 16 mg/kg.

Exploratory biomarker analyses indicated that B7-H3 expression did not demonstrate significant predictive value for treatment outcomes. Preliminary findings suggested a potential association between SLFN11 expression and clinical activity. 

Grade ≥3 treatment-related adverse events occurred in 47.5% of patients receiving 12 mg/kg and 61.9% of patients receiving 16 mg/kg, and most frequently included decreased white blood cell count (15% vs 28.6%), decreased lymphocyte count (10% vs 28.6%), decreased platelet count (10% vs 9.5%), and anemia (7.5% vs 19%). 

Treatment-related adverse events led to treatment discontinuation in 2.5% of patients receiving 12 mg/kg, while no treatment-related adverse discontinuations were reported in the 16 mg/kg cohort. 

Investigators concluded that SKB500 demonstrated a more favorable preliminary safety profile and greater antitumor activity at 12 mg/kg compared with 16 mg/kg, supporting further clinical development in patients with SCLC.

Source:

Zhang X, Liu H, Zheng W, et al. SKB500 (a novel B7-H3–targeted antibody-drug conjugate) in patients with extensive-stage small cell lung cancer (ES-SCLC): Results from a phase I study. Presented at the ESMO Congress. October 23–27, 2026; Madrid, Spain. Abstract 3816RO.