Early Promise for TROP2-Targeted ADC in Treating Gastric Cancer

A recent study presented at the 2024 American Association for Cancer Research (AACR) annual meeting has shown that the antibody-drug conjugate (ADC) SKB264, developed by Merck and Kelun-Biotech, has shown significant potential in managing disease and possibly extending the lives of patients suffering from gastric or gastroesophageal junction cancer who have undergone extensive prior treatment.

The ADC, SKB264, targets the TROP2 cell surface protein, which is a recognized biomarker in gastric cancer and is linked to a poorer prognosis. In the trial, it demonstrated an objective response rate of 22% among 41 patients, with nine achieving partial remission. The disease control rate for these patients was an impressive 80.5%, and the median duration of response was 7.5 months.

Notably, in a group of 24 patients who had undergone at least two previous treatments, SKB264 not only improved disease control but also enhanced survival rates. The median progression-free survival for this subgroup was 3.7 months, and the median overall survival was 7.6 months, with a 12-month overall survival rate of 32.6%.

The innovative aspect of SKB264 lies in its design, which includes a novel linker that is sensitive to pH changes near the tumor and is also cleaved by enzymes within cancer cells. This allows for a targeted delivery of the belotecan-derivative topoisomerase I inhibitor, a toxic payload that induces DNA damage and leads to cell death.

Jordi Rodon, the lead author of the study and an associate professor at the MD Anderson Cancer Center, highlighted the importance of the linker-payload combination in the ADC's effectiveness and safety profile. He also mentioned that unlike other ADCs targeting the same protein, SKB264 did not cause interstitial lung diseases, which is a significant advancement.

Following the positive results, MD Anderson Cancer Center announced plans for a global Phase III study to compare SKB264 with the current standard of care for patients who have received at least three prior treatments for gastric or gastroesophageal junction adenocarcinomas.

Merck, which holds worldwide rights to SKB264 (excluding the Greater China region), has been exploring its potential in various types of cancer. In addition to gastric cancer, the company is conducting a Phase III study for triple-negative breast cancer and a Phase II trial for non-small cell lung cancer and other advanced tumors. The partnership between Merck and Kelun, a subsidiary of Sichuan Kelun Pharmaceutical, has been instrumental in advancing oncology research and treatment options.

The findings from the AACR meeting underscore the promising future of targeted cancer therapies and the potential for ADCs like SKB264 to transform the treatment landscape for patients with limited options due to prior treatments.