KEY TAKEAWAYS
- The phase 1 & 2 trials aimed to investigate the efficacy and safety of SKB264 in patients with advanced NSCLC, leveraging its TROP2 targeting and novel payload delivery mechanism.
- Researchers noticed continued promising efficacy and manageable toxicity of SKB264 monotherapy in patients with previously treated advanced NSCLC.
TROP2 (trophoblast cell surface antigen 2) is commonly overexpressed in non-small cell lung cancer (NSCLC) and is associated with poor prognosis. SKB264 (MK-2870) is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. The linker undergoes extracellular pH-sensitive cleavage and intracellular enzymatic cleavage within tumor cells, facilitating efficient payload release both intracellularly and within the tumor microenvironment, thus exerting anti-tumor effects.
Wenfeng Fang and the team aimed to present updated data from a Phase 2 expansion cohort for patients with advanced NSCLC.
They performed an inclusive analysis on patients with previously treated advanced NSCLC who were enrolled to receive SKB264 at 5 mg/kg Q2W until disease progression or unacceptable toxicity (KL264-01, NCT04152499). As evaluated by the investigator, tumor assessment was conducted every 8 weeks per RECIST v1.1.
About 43 NSCLC patients had been enrolled as of Nov 22, 2023, with a median follow-up of 17.2 months. Among them, 21 patients with EGFR wild type had received a median of 3 prior therapy regimens, including anti-PD-1/L1 inhibitors. Twenty-two patients with EGFR mutations had progressed on or after TKI therapy, with 50% experiencing failure in at least one line of chemotherapy.
Updated efficacy results showed that 30 patients (69.8%) experienced Grade ≥3 treatment-related adverse events (TRAEs). The most common Grade ≥3 TRAEs were decreased neutrophil count (34.9%), anemia (30.2%), decreased WBC count (25.6%), stomatitis (9.3%), and rash (7.0%). No TRAEs led to treatment discontinuation or deaths, and no drug-related ILD/pneumonitis was reported.
The study concluded that SKB264 monotherapy exhibits promising clinical efficacy with manageable toxicity in previously treated advanced NSCLC patients. Ongoing Phase 3 trials globally and in China aim to further evaluate SKB264 in EGFR mutant NSCLC populations.
The trial was sponsored by Klus Pharma Inc.
Source: https://www.abstractsonline.com/pp8/#!/20272/presentation/11568
Clinical Trial: https://clinicaltrials.gov/study/NCT04152499
Fang W., Cheng Y., Chen Z., et al. (2024). “Updated efficacy and safety of anti-TROP2 ADC SKB264 (MK-2870) for previously treated advanced NSCLC in Phase 2 study.” Presented at AACR (Abstract CT247 / 6).
