Silexion Therapeutics has announced positive data from its Phase 2 trial of LODER™ in patients with non-resectable locally advanced pancreatic cancer (LAPC) harboring KRAS G12D or G12V mutations. The trial results indicate a significant objective response rate (ORR) and improved resectability, offering a potential new treatment avenue for this challenging cancer.
The updated analysis of the Phase 2 trial reveals a 56% ORR in patients treated with LODER. Notably, the ORR increased to 67% in patients whose tumors, initially deemed non-resectable, became eligible for surgical removal following LODER treatment. This suggests that LODER may improve surgical outcomes for LAPC patients who would otherwise have limited options.
Survival Benefit
In addition to improved resectability, previous data from the trial showed that patients treated with LODER in combination with standard-of-care (SoC) chemotherapy experienced a 9.3-month improvement in overall survival (OS) compared to those treated with chemotherapy alone. This survival benefit underscores the potential of LODER to extend the lives of patients with advanced pancreatic cancer.
Next-Generation Therapy: SIL-204
Silexion is also developing SIL-204, a next-generation product designed to target a broader range of KRAS mutations, including pan-G12x and G13D. Preclinical studies suggest that SIL-204 has improved stability and an enhanced ability to silence the KRAS oncogene, potentially making it a more effective treatment option for difficult-to-treat cancers like LAPC.
Management Commentary
"We are very encouraged by these new findings, which demonstrate LODER's ability to significantly improve tumor resectability in patients with non-resectable pancreatic cancer, and the improved profile of SIL-204," said Ilan Hadar, Chairman and CEO of Silexion. "As we advance our broader pipeline to address KRAS-driven cancers, this data further validates our oncogene silencing approach."
Trial Design
The open-label Phase 2 trial enrolled 48 patients with non-resectable LAPC and borderline resectable pancreatic cancer (BRPC) across the U.S. and Israel. The trial was conducted in two parts:
- Cohort 1 (n=29): Patients were randomized 1:1 to receive either LODER with SoC chemotherapy or SoC chemotherapy alone. The primary endpoint was overall survival (OS), with 16 patients confirmed to harbor the KRAS G12D/V mutation.
- Cohort 2 (n=19): This cohort enrolled patients with non-resectable tumors, LAPC or BRPC, with the key endpoints focused on ORR and safety. Seven patients in this cohort were confirmed to have KRAS G12D/V mutations.
The objective response rate was evaluated for 23 patients with confirmed KRAS G12D/V mutations across both cohorts.
