$艾吉纳斯公司(AGEN)$$安帝君斯(AGEN)$ MSS CRC取得的一点点小突破，下一代CTLA-4呼之欲出

Study Highlights

A total of 41 evaluable patients with metastatic MSS CRC received either 1 or 2 mg/kg botensilimab Q6W, and 3 mg/kg balstilimab Q2W. Patients were heavily pre-treated, with a median of 4 prior lines of therapy, and 34% had received prior immunotherapy. The botensilimab/balstilimab combination produced superior responses and strong durability, relative to what has been reported in separate trials for standard of care and other combinations currently in development.

Objective responses:

24% overall response rate73% disease control rate (partial response + stable disease)50% objective responses with greater than 50% tumor reduction

Durability:

80% objective responses ongoing at data cut-off30% objective responses exceeding 1 year

Patient Sub-Populations:

Objective responses in 5 patients with RAS mutations for a 24% overall response rate and 81% disease control rate in this population; other PD-1 combinations in separate trials have reported only rare responses in this population (≤1% response rate)Responses observed in patients with metastases historically resistant to immunotherapy, including patients with malignant pleural effusions, soft tissue, peritoneal, retroperitoneal, and bone metastases

Tolerability:

Botensilimab was well tolerated, with no grade 4/5 treatment-related adverse eventsRates of gastrointestinal and skin toxicities were comparable to those reported with first-generation CTLA-4 inhibitors

“Colorectal cancer is the second leading cause of cancer-related death worldwide, with roughly 95% classified as microsatellite stable and historically unresponsive to immunotherapy. Treatment resistant MSS CRC patients lack effective options, with standard of care offering only a 1-2% response rate and a median expected survival ranging from 6 to 7 months,” said Anthony El-Khoueiry, MD, Phase I Program Director at the USC Norris Comprehensive Cancer Center, Keck Medicine of USC. “The combination of robust response rate, durability, and tolerability demonstrated by botensilimab and balstilimab supports further development of the combination in MSS CRC, as well as more broadly, in other cold and treatment-resistant tumors.”