Merck’s ADC SKB264 Shows Promising Results in Advanced Gastric Cancer: Phase 2 Data Reveals Potent Anti-Tumor Activity and Manageable Safety Profile ─ AACR 2024 (Abstract CT038)

Overexpression of TROP2 (trophoblast cell surface antigen 2) in advanced gastric cancer has been identified as a poor prognostic factor. SKB264 (MK-2870) is a TROP2 ADC (Antibody-Drug Conjugate) designed with a unique linker to attach the payload, a belotecan-derivative topoisomerase I inhibitor. This linker undergoes cleavage in response to both extracellular pH and intracellular enzymes within tumor cells, facilitating efficient release of the payload both inside tumor cells and within the tumor microenvironment, thereby exerting its anti-tumor effects.

As of November 22, 2023, 48 patients with advanced gastric cancer were enrolled in a Phase 2 study evaluating SKB264. Half had received one prior line of therapy (2L), while the other half had received two or more prior lines (3L+), with a majority having received prior anti-PD-1/L1 inhibitors.

Safety Profile: Treatment-related adverse events (TRAEs) of Grade 3 or higher were reported in 52.1% of patients. The most common were anemia, decreased neutrophil count, and neutropenia. Despite these, TRAEs leading to dose reductions or delays occurred in a minority of patients, with no treatment discontinuations or deaths related to SKB264. Notably, neuropathy and drug-related interstitial lung disease/pneumonitis were absent.

Efficacy Results: Of the evaluable patients, the objective response rate (ORR) was 22.0%, with a disease control rate (DCR) of 80.5%. ORRs were higher in the 2L group compared to 3L+. The median duration of response (DoR) was 7.5 months. In 3L+ patients, median progression-free survival (mPFS) was 3.7 months, and median overall survival (mOS) was 7.6 months, with a 12-month OS rate of 32.6%.

These findings suggest a potential clinical benefit of SKB264 monotherapy in advanced gastric cancer, especially in heavily pre-treated patients. Its manageable safety profile and modest but notable efficacy outcomes warrant further exploration. The planned Phase 3 study comparing SKB264 to standard of care in 3L+ gastric/GEJ adenocarcinoma highlights the significance of these preliminary findings.

Conclusion: SKB264 demonstrates promise as a treatment option for advanced gastric cancer, particularly in patients who have exhausted standard therapies. Further research in larger cohorts and comparative studies will be pivotal in confirming its clinical utility and establishing its role in the treatment landscape. Ongoing monitoring for long-term safety and efficacy outcomes will be essential for informing treatment decisions in real-world clinical practice.

For more information, refer DelveInsight’s reports:

Gastroesophageal Junction Adenocarcinoma – Market Insight, Epidemiology and Market Forecast – 2032

Gastric Cancer – Market Insight, Epidemiology And Market Forecast – 2032