514O - An open-label, global, first-in-human study of SKB264 in patients with locally advanced or metastatic solid tumors

Background

SKB264 is an antibody drug conjugate (ADC) composed of an antibody targeting the trophoblast cell-surface antigen 2 (TROP2), which is overexpressed in many types of solid tumors, coupled to moderate cytotoxic belotecan-derivative through a novel linker which was designed to balance the extracellular stability and intracellular rupture. We hereby report initial results of the FIH study (NCT04152499; CTR20201069).

Methods

Patients (pts) aged ≥18 with unresectable solid tumors refractory to/relapsed from standard treatment with measurable disease per RECIST 1.1 will be enrolled and receive SKB264 Q2W every 4 weeks as monotherapy. The objectives are to determine the safety, tolerability, pharmacokinetics (PK) and antitumor activity of SKB264.

Results

The dose escalation study is still ongoing. As of March 15, 2021, 18 pts were enrolled in 3 dose levels (2, 4 and 6 mg/kg). Treatment emergent adverse events (TEAEs) regardless of causality were reported in 18 of 18 pts, the most common TEAEs were Grade (G) 1-2 nausea (72.2%) and alopecia (66.7%). The most common≥G3 TEAEs were neutrophil count decreased (27.8%), white blood cell count decreased (22.2%), and anemia (16.7%). The above ≥G3 AEs were recovered after corresponding treatment. No TEAE led to death. The PK results suggest that exposure of SKB264 increased proportionally with dose, and no accumulation observed after multiple doses. The half-lives of SKB264 and free payload are approximately 36 hours and 49 hours respectively, which support the dose regimen of Q2W. Serum free payload was about 6% and 5% of total SKB264 (ADC) Cmax and AUC respectively in Cycle 1, indicated the stable novel linker of SKB264 in the serum. A total of 17 pts had undergone at least one tumor assessment, and preliminary efficacy was observed in all dose levels from 2 to 6 mg/kg. Six patients had Partial Response per RECIST 1.1: 2 triple-negative breast cancer (40%, 2/5), 2 ovarian cancer (40%, 2/5), 1 HER2+breast cancer (100%, 1/1), and 1 gastric adenocarcinoma (100%, 1/1). The Overall Response Rate (ORR) is 35.3% (6/17) and the Disease Control Rate (DCR) is 70.6% (12/17).

Conclusions

SKB264 has demonstrated encouraging safety and antitumor activity. Study continues to identify dose(s) of SKB264.

Clinical trial identification

NCT04152499 November 5, 2019.

Editorial acknowledgement

Legal entity responsible for the study

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Funding

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.