SKB246 Led to Disease Control, Durable Response in Gastric Cancers

SKB264 led to disease control and durable responses for pretreated patients with gastric or gastroesophageal junction cancers, recent data showed.

Treatment with the antibody-drug conjugate (ADC) SKB264 (sacituzumab tirumotecan, also known as sac-TMT and MK-2870) for pretreated patients with gastric or gastroesophageal junction cancers may result in disease control and durable responses, according to preliminary data from a phase 1/2 study presented at the American Association for Cancer Research (AACR) Annual Meeting 2024.

SKB264, as explained in a news release from The University of Texas MD Anderson Cancer Center in Houston, targets the TROP2 protein, which is commonly associated with poor prognosis in advanced gastric cancers. It uses a novel linker to connect an antibody with the drug’s “payload,” a belotecan-derivate topoisomerase I inhibitor.

“The anti-TROP2 antibody targets and binds to TROP2 expressed on tumor cells,” the National Cancer Institute explained on its website. “Upon cellular uptake, the undisclosed toxin exerts … its cytotoxic effect. This inhibits tumor cell proliferation of TROP2-expressing tumor cells.”

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“It is interesting to note the change in antitumor activity and safety profile that results from changing payloads and linkers, even among ADCs aiming at the same target,” stated Dr. Jordi Rodon, associate professor of investigational cancer therapeutics at MD Anderson Cancer Center, who presented the study’s findings at AACR, in the news release. “One of the big results of this trial is that, by using a different linker-payload combination, we did not see the interstitial lung diseases associated with other ADCs.”

Among 41 previously treated, inoperable patients who were evaluable for response, SKB264 elicited an objective response rate (the percentage of patients whose disease responded partially or completely to treatment) of 22% as well as a disease control rate (the percentage of patients whose disease disappeared, shrunk or was stabilized) of 80.5% and a duration of response of 7.5 months, according to the announcement from MD Anderson Cancer Center.

Regarding 24 patients who had received at least two prior lines of therapy, 54.2% of whom had received at least four prior lines of therapy, with a median follow-up of 14.6 months, the median progression-free survival (the time a patient lives without their disease spreading or worsening) was 3.7 months and median overall survival (the time a patient lives following treatment, regardless of disease status) was 7.6 months. The 12-month overall survival rate of 32.6%, researchers stated in an abstract of their findings posted to the AACR meeting website.

“The preliminary data suggests that pts with heavily pre-treated advanced G/GEJ cancer could achieve durable response and potentially prolonged OS from SKB264 monotherapy, with a manageable safety profile,” researchers wrote.

For the 48 patients who were evaluable for safety with a minimum follow-up of nine weeks after the data cutoff, treatment-related side effects more severe than grade 3 were reported in 52.1% of patients. The most common side effects included anemia (low red blood cell count), decreased white blood cell counts and neutropenia (low counts of neutrophils, a type of white blood cell). There were 18.8% of patients who had to decrease their dosage of the drug, and 33.3% had to delay dosing due to side effects, according to the news release from MD Anderson Cancer Center, which also noted that no side effects resulted in discontinuation of the trial or death.

Subsequently, MD Anderson Cancer Center stated, a global phase 3 study is now being planned evaluating SKB264 against the current standard of care for patients with gastric or gastroesophageal junction adenocarcinoma who have received at least three prior lines of therapy.

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